Biochemistry Viva Questions

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1. Cell Organells ....................................................... 1

2. Cell Membranes: Structure and Function ....... 3

3. Amino Acids: Structure and Properties ........... 8

4. Proteins: Structure and Function .................... 17

5. Enzymology-I ..................................................... 27

6. Enzymology-II: Iso-Enzymes andClinical Enzymology ......................................... 40

7. Methods of Separation & Purification ofBiological Compounds, Methods ofStudy of Metabolism ......................................... 47

8. Carbohydrates-I:Chemistry, Digestion andAbsorption .......................................................... 52

9. Carbohydrates-II: Major MetabolicPathways of Glucose, Glycolysis,Gluconeogenesis, Glycogen Metabolism ...... 61

10. Carbohydrates-III: Regulation of BloodSugar, Insulin and Diabets Mellitus .............. 70

11. Carbohydrates-IV: Other Metabolic Pathways(HMP Shunt Pathway, Fructose, Galactose,Glucuronic Acid, Alcohol) ................................ 81

ContentsContentsContentsContentsContents

2 Viva�based on Textbook of Biochemistry

12. Lipids-I: Chemistry, Digestion andAbsorption of Lipids ......................................... 88

13. Lipids-II: Metabolism of Fatty acids, Fatty acidoxidation, Fatty acid synthesis, Lipolysis,Ketone bodies ..................................................... 95

14. Lipids-III: Cholesterol, Lipoproteins andCardiovascular Diseases ................................. 103

15. Lipids-IV: MCFA, PUFA andProstaglandins .................................................. 112

16. Lipids-V: Compound Lipids ......................... 118

17. Amino Acid Metabolism-I:General: Digestion, Absorption,Transamination, Urea ...................................... 122

18. Amino Acid Metabolism-II: Simple,Hydroxy and Sulfur Containing AminoAcids Glycine, Serine, Alanine, Threonine,Methionine, Cysteine ...................................... 128

19. Amino Acid Metabolism-III: Acidic, Basic andBranched Chain Amino Acids, Glutamic acid,Glutamine, Aspartic acid, Asparagine, Lysine,Nitric Oxide, Valine, Leucine, Isoleucine .... 132

20. Amino Acid Metabolism-IV: Aromatic AminoAcids: Phenyl alanine, Tyrosine, Tryptophan,Histidine ............................................................ 137

21. Amino Acid Metabolism-V: Inter-relations ofAmino Acid Metabolisms, One CarbonMetabolism, Amino Acidurias ...................... 142

Contents 3

22. Citric Acid Cycle .............................................. 144

23. Electron Transport Chain ............................... 147

24. Free Radicals and Anti-oxidants ................... 151

25. Plasma Proteins ................................................ 153

26. Immunochemistry ............................................ 156

27. Specialised Proteins: Collagen, Myosin ...... 158

28. Heme Synthesis and Breakdown ................. 160

29. Haemoglobins .................................................. 165

30. Vitamin-I: Fat Soluble Vitamins: A, D, Eand K .................................................................. 169

31. Vitamin-II: Water soluble vitamins .............. 174

32. Mineral Metabolism ........................................ 189

33. Energy Metabolism and Nutrition ............... 195

34. Detoxification and Biotransformation ofXenobiotics ........................................................ 199

35. Biochemical Aspects of EnvironmentalPollution ............................................................ 201

36. Acid Base Balance and pH ............................. 203

37. Electrolyte and Water Balance ....................... 207

38. Molecular Biology-I: Nucleotides, Chemistryand Metabolism ............................................... 209


39. Molecular Biology-II: DNA structure andReplication ........................................................ 216

40. Molecular Biology-III: Transcription andTranslation ........................................................ 220

41. Molecular Biology-IV: Molecular Geneticsand Control of Gene Expression ................... 227

42. Molecular Biology-V: Recombinant DNATechnology and Gene Therapy .................... 229

43. Biochemistry of AIDS ..................................... 233

44. Biochemistry of Cancer ................................... 235

45. Applications of Radio-isotopes inMedicine ............................................................ 238

46. Body Fluids ....................................................... 240

47. Hormones-I: Mechanism of Action ofHormones .......................................................... 242

48. Hormones-II: Pituitary Hormones ................ 244

49. Hormones-III: Steroid Hormones ................. 246

50. Hormones-IV: Thyroid Hormones ............... 248

51. Clinical Biochemistry-I: .................................. 250

52. Clinical Biochemistry-II: Liver andGastric Function Tests ..................................... 252

53. Clinical Biochemistry-III: Kidney FunctionTests .................................................................... 256

Cell Organelles 1

Cell Organelles

Q. What is the function of Golgi complex?

A. Maturation and processing of nascent proteins,glycosylation of proteins, secretion newlysynthesised proteins (Page 3).

Q. What is the function of endoplasmic reticulum?(Page 3)

A. Biosynthesis of proteins, drug metabolism,desaturation of fatty acids.

Q. What is the marker enzyme for endoplasmicreticulum?

A. Glucose-6-phosphatase (Page 3, Table 1.3).

Q. Where does protein synthesis take place?

A. On the walls of endoplasmic reticulum and alsoin cytosol (Page 3).

Q. What are cathepsins?

A. They are intracellular proteolytic enzymes(Page 4).


Q. What is the function of lysosomes?

A. They are bags of hydrolytic enzymes that bringabout degradation of macromolecules (Page 4).

Q. What is lysozyme?

A. It is an enzyme present in external secretions(Page 35).

Q. What are peroxisomes?

A. They contain peroxidase and catalase, necessaryfor destroying the unwanted free radicals.

(Page 4)

Q. What are the important metabolic events takingplace in cytoplasm?

A. Glycolysis (Embden-Meyerhof pathway), HMPshunt pathway, glycogen metabolism, Fatty acidsynthesis, Synthesis of nucleotides, Degradationof amino acids (See Page 5, Table 1.4).

Q. What is the function of mitochondria?

A. Generation of ATP (See page 5).

Q. What are the important metabolic events takingplace in mitochondria?

A. TCA cycle, electron transport chain, beta oxida-tion of fatty acids and urea cycle (Page 5).

Cell Membranes; Structure and Function 3

Q. What are ecto-enzymes?

A. They are enzymes seen on the outer part of cellmembrane (Page 6).

Q. Give examples of ecto-enzymes.

A. Alkaline phosphatase, 5�nucleotidase (Page 6).

Q. How do you describe the structure of cell mem-brane?

A. Fluid mosaic model (Page 6).

Q. What are the characteristics of fluid mosaicmodel?.

A. Membrane is composed of lipid bilayer. Phospho-lipids are arranged in bilayers with a hydropho-bic core (Page 6).

Q. What do you mean by fluidity of the membrane?

A. The lipid bilayer shows free lateral movement ofits components; but flip-flop movement is re-stricted (Page 6).

Cell Membranes:Structure and Function


Q. What are the components of membrane that al-ter the fluidity?

A. Cholesterol and unsaturated fatty acids (Page 6).

Q. What are the different types of transport mecha-nisms?

A. Passive and active. Passive type is subclassifiedas simple diffusion and facilitated diffusion(Page 8).

Q. What are the salient features of facilitated diffu-sion?

A. It is carrier mediated. It does not require energydirectly (Page 8).

Q. Can you give an example of facilitated transport?

A. Glucose transporters (Page 8).

Q. What are ion channels?

A. They are special devices for quick transport ofelectrolytes (Page 9).

Q. Give some examples of ion channels.

A. Ion channels specific for calcium, potassium andchloride (Page 9).

Q. What are ionophores?

A. They are transport antibiotics which increase thepermeability of membrane to ions, e.g. valinomy-cin, gramicidin (Page 10).

Q. What are the salient features of active transport?

A. It requires transporters. It requires energy. Trans-port is generally unidirectional (Page 10).


Q. Give examples of active transport systems.

A. Sodium pump, calcium pump (Page 10).

Q. What is the importance of sodium pump?

A. Cell has low intracellular sodium; but concentra-tion of potassium inside the cell is high; this ismaintained by sodium pump. About 40% of thetotal energy expenditure in a cell is used for thisactive transport system (Page 10).

Q. How does sodium pump work?

A. It is called sodium-potassium activated ATPase.Hydrolysis of one molecule of ATP can result inexpulsion of 3 sodium ions and influx of 2 potas-sium ions (Page 10).

Q. What is its clinical significance?

A. Digoxin increases the contractility of the cardiacmuscle, by inhibiting the sodium pump (Page10).

Q. What is a uniport?

A. It carries single solute across the membrane(Page 10).

Q. Give examples of uniport.

A. Glucose transporter (GluT2) operating in most ofthe cells is an example. Calcium pump is anotherexample (Page 10).

Q. What is co-transport?

A. If transfer of one molecule depends on simulta-neous or sequential transfer of another molecule,it is called co-transport system (Page 10).


Q. How are co-transport systems classified?

A. The cotransport system may be symport orantiport (Page 10).

Q. What is symport?

A. In symport, the transporter carries two solutes inthe same direction across the membrane (Page10).

Q. Give examples of symport. (Page 10)A. Sodium dependent glucose transporter (SgluT)

(Fig.8.31). Phlorhizin, an inhibitor of sodium-de-pendent cotransport of glucose, especially in theproximal convoluted tubules of kidney, producesrenal damage and results in renal diabetes. Aminoacid transport is another example for symport.

Q. What is antiport system?. (Page 10)A. The antiport system carries two solutes or ions in

opposite direction.

Q. Give examples of antiport. (Page 10)A. Sodium pump (Fig.2.7) or chloride-bicarbonate

exchange in RBC (Fig.29.4).

Q. What is endocytosis?. (Page 11)A. It is the mechanism by which cells internalise ex-

tracellular macromolecules.

Q. What is pinocytosis?. (Page 11)A. It is receptor mediated. Low Density Lipoprotein

(LDL) binds to the LDL receptor and the complexis later internalised. These vesicles are coated withClathrin. .


Q. What is phagocytosis. (Page 11)A. It is the engulfment and internalisation of large

particles such as bacteria by macrophages andgranulocytes.

Q. What is respiratory burst. (Page 11)A. During phagocytosis, there is an increase in oxy-

gen consumption with formation of the superox-ide ion.


Amino Acids:Structure andProperties

Q. How do you classify amino acids? (Page 12)A. Based on the structure, amino acids are classified

into: Simple amino acids, Branched chain aminoacids, Hydroxy amino acids, Sulfur containingamino acids, Amino acids with amide group,Acidic amino acids, Basic amino acids, Aromaticamino acids, Heterocyclic amino acids, Imino acidand Derived amino acids.

Q. What are branched chain amino acids?(Page 12)A. Valine, leucine and isoleucine.

Q. What are hydroxy amino acids? (Page 12)A. Serine and threonine.

Q. Name the Sulfur containing amino acids.(Page 12)

A. Cysteine and methionine.

Q. Name the acidic amino acids. (Page 12)A. Aspartic acid and glutamic acid.

Amino Acids: Structure and Properties 9

Q. What are the basic amino acids? (Page 12)A. Lysine and arginine.

Q. Which amino acid has a net positive charge atphysiological pH? (Page 12)

A. Arginine and lysine.

Q. Amino acid containing a thio-ether bond is.(Page 12)

A. Methionine.

Q. Give examples of amino acids with hydropho-bic side chains. (Page 12)

A. Valine, leucine, isoleucine.

Q. Give the names of aromatic amino acids.(Page 12)

A. Phenylalanine and tyrosine.

Q. What are heterocyclic amino acids? (Page 12)A. Tryptophan and histidine.

Q. Give an example of an imino acid. (Page 12)A. Proline.

Q. Give examples of derived amino acids.(Page 12)A. Hydroxy proline, hydroxy lysine, ornithine, cit-

rulline, homocysteine.

Q. Arginine contains which special group?(Page 12)

A. Guanidinium group (-NH-CNH-NH2).

Q. Benzene group is present in which amino acid?(Page 12)

A. Phenyl alanine.


Q. Phenol group is present in which amino acid?(Page 12)

A. Tyrosine.

Q. Tryptophan contains what special group?

(Page 12)A. Indole group.

Q. Which special group is present in Histidine?(Page 12)

A. Imidazole group.

Q. Name some hydrophobic amino acids.(Page 12)A. Valine, leucine and isoleucine.

Q. Pyrrolidine group is present in which aminoacid? (Page 12)

A. Proline.

Q. Hydrophobic bonds are formed in protein be-tween which amino acids?

A. Valine, leucine and isoleucine residues.(Page 12)

Q. What is the basis of classification of amino acidsinto ketogenic and glucogenic?

(Page 12 and 13)A. Ketogenic amino acids enter into the metabolic

pathway of fats, while glucogenic amino acidsenter the pathway of glucose metabolism.

Q. Name a purely ketogenic amino acid.(Page 12)

A. Leucine.

Q. Name some glucogenic amino acids. (Page 13)A. Glycine; serine; aspartic acid.


Q. Which amino acid is synthesised after it gets in-corporated into the protein?

A. Hydroxyproline (Page 12).

Q. What are essential amino acids? (Page 13)A. They cannot be synthesized in the body; and so,

they are to be provided in the diet.

Q. How many amino acids are essential? (Page 13)A. Eight amino acids are essential; two are semi-es-

sential and the rest 10 are non-essential.

Q. Are non-essential amino acids necessary for thebody?

A. They are also necessary for protein synthesis, butthey can be synthesized by the body and neednot be essentially present in the diet (Page 14).

Q. Name any three essential amino acids. (Page 13)A. Isoleucine, leucine, threonine.

Q. Is phenyl alanine an essential amino acid?(Page 13)

A. Yes.

Q. What about Tyrosine? (Page 13)A. Tyrosine is non-essential, it is synthesized from

phenyl alanine.

Q. Name the semi-essential amino acids. (Page 14)A. Histidine and arginine.

Q. Why are they called semi-essential? (Page 14)A. Because growing children require them in food.

But they are not essential for the adult individual.


Q. What is iso-electric point?. (Page 14)A. The pH at which the molecule carries no net charge

is called iso-electric point.

Q. What are the characteristic features of iso-elec-tric pH. (Page 14)

A. At iso-electric point the amino acid will carry nonet charge, there is no mobility in electrical field,solubility will be minimum, the tendency for pre-cipitation will be maximum

Q. What is the speciality of Histidine? (Page 14)A. The pK value of Histidine is 6.1, and therefore

effective as a buffer at the physiological pH of 7.4.The buffering capacity of plasma proteins andhemoglobin is mainly due to histidine residue.

Q. Which is the amino acid having maximum buff-ering capacity at physiological pH? (Page 14)

A. Histidine.

Q. Which amino acid is optically inactive?(Page 15)

A. Glycine.

Q. What are the isomers of amino acids? (Page 16)A. D and L varieties.

Q. What are natural amino acids? (Page 16)A. Only L amino acids are seen in large quantities in

nature.


Q. Can you name some substances where D-aminoacids are seen?

A. D-amino acids are seen in cell walls of micro-or-ganisms and as constituents of certain antibioticssuch as gramicidin-S, polymyxin, actinomycin-Dand valinomycin (Page 16).

Q. What is meant by decarboxylation of an aminoacid? (Page 16)

A. The carboxyl group is removed from the aminoacids to form the corresponding amine (Fig.3.8).

Q. Give examples of decarboxylation reactions.(Page 16)

A. Histidine to histamine; tyrosine to tyramine; tryp-tophan to tryptamine.

Q. What is produced when Glutamic acid is decar-boxylated? (Page 16)

A. Gamma amino butyric acid or GABA.

Q. What is glutamine? (Page 16)A. That is the amide of glutamic acid.

Q. What is an amide? (Page 16)A. The extra carboxyl group (other thanÿalpha car-

boxyl) can combine with ammonia to form the cor-responding amide.

Q. How asparagines is produced? (Page 16)A. Aspartic acid + ammonia will form asparagine.

Q. What is transamination? (Page 16)A. The alpha amino group of amino acid can be trans-

ferred to alpha keto acid to form the correspond-ing new amino acid and alpha keto acid (Fig.3.10).


Q. Give an example of transamination reaction.(Page 16)

A. Glutamic acid + pyruvic acid alpha keto glutarate+ alanine.

Q. What is the product of transamination reactionof pyruvate with glutamate?

A. Alanine and alpha keto glutarate (Page 16).

Q. What is the biological significance of transami-nation reaction?

A. These are important for the interconversion ofamino acids. Non-essential amino acids are syn-thesized by this process (Page 16).

Q. What is the clinical significance of transami-nases? (Page 16)

A. Transaminases in blood are elevated in liver andheart diseases.

Q. What is the significance of SH groups in pro-teins? (Page 17)

A. The SH group of cysteine can form a disulfide (S-S) bond with another cysteine residue. The twocysteine residues can connect two polypeptidechains by the formation of interchain disulfidebonds.

Q. Glutathione is made up of which amino acids?(Page 17)

A. Glutamic acid, cysteine and glycine.

Q. Phosphorylation is taking place on which aminoacid residue?

A. Serine (Page 17).


Q. What is ninhydrin reaction? (Page 18)A. All amino acids when heated with ninhydrin will

give a pink colour.

Q. What is the importance of ninhydrin reaction?(Page 18)

A. It is used for qualitative test and quantitative es-timation of amino acids. It is often used for detec-tion of amino acids in chromatography.

Q. Do proteins give a color with ninhydrin?(Page 18)

A. Proteins do not give a true color reaction; but N-terminal end amino group of protein will reactwith ninhydrin, to produce a blue color.

Q. What is biuret reaction? (Page 18)A. Cupric ions in alkaline medium form a violet

colour with peptide bond nitrogen.

Q. Will amino acids give a positive biuret test?(Page 18)

A. No. This needs a minimum of two peptide bonds.

Q. What is the use of biuret reaction? (Page 18)A. This reaction can be used for qualitative identifi-

cation and quantitative estimation of proteins.

Q. What is biuret? (Page 18)A. The name is derived from the compound biuret,

a condensation product of two urea molecules,which also gives a positive color test.


Q. What is the basis of xanthoproteic test?(Page 18)

A. The ring systems in phenyl alanine, tyrosine andtryptophan will answer this test.

Q. The protein which does not answer the aldehydetest is. (Page 18)

A. Gelatin.

Proteins: Structure and Function 17

Q. How proteins are made up of? (Page 19)A. Proteins are made by polymerisation of amino

acids through peptide bonds.

Q. What is a peptide bond? (Page 19)A. Alpha carboxyl group of one amino acid reacts

with alpha amino group of another amino acid toform a peptide bond or CO-NH bridge (Fig. 4.1).

Q. What is a dipeptide? (Page 19)A. Two amino acids are combined to form a dipep-

tide.

Q. How many peptide bonds are present in a trip-eptide? (Page 19)

A. A tripeptide is a combination of three amino ac-ids; so there are two peptide bonds.

Q. What is a polypeptide? (Page 19)A. A combination of 10 to 50 amino acids is called as

a polypeptide.

Proteins: Structureand Function


Q. What is the difference between a polypeptideand a protein? (Page 19)

A. A combination of 10 to 50 amino acids is called apolypeptide. By convention, chains containingmore than 50 amino acids are called proteins.

Q. What are the levels of organizations of proteins?(Page 19)

A. Proteins have primary, secondary, tertiary andquaternary levels of organisation.

Q. What is meant by primary structure of a protein?(Page 19)

A. It denotes the number and sequence of amino ac-ids in the protein.

Q. What is the force that maintains the primarystructure? (Page 19)

A. The primary structure is maintained by the cova-lent bonds of the peptide linkages (Fig. 4.2).

Q. What are the salient features of a peptide bond?(Page 19)

A. The peptide bond is a partial double bond. TheC-N bond is �trans� in nature and there is no free-dom of rotation because of the partial double bondcharacter.

Q. What is the N-terminal end of a protein?(Page 20)

A. In a protein, at one end there will be one free al-pha amino group. This end is called the aminoterminal (N-terminal) end and the amino acid con-tributing the ?-amino group is named as the firstamino acid.


Q. What are the names for the end amino acids ofproteins. (Page 20)

A. The end where there is a free alpha amino groupis called the amino terminal (N-terminal) end. Theother end of the polypeptide chain is called thecarboxy terminal end (C-terminal) where there isa free alpha carboxyl group.

Q. Can you give an example of a pseudopeptide?(Page 20)

A. Glutathione (gamma-glutamyl-cysteinyl-glycine).The pseudopeptide a peptide bond formed bycarboxyl group, other than that of alpha position.

Q. What are the salient structural features of insu-lin? (Page 20)

A. It has two polypeptide chains. These chains areheld together by disulfide bridges. Insulin hastotal 51 amino acids.

Q. What is pro-insulin? (Page 20)A. Insulin is synthesised by the beta cells of pancreas

as a prohormone, proinsulin is a single poly-pep-tide chain with 86 amino acids.

Q. What is mutation? (Page 20)A. Amino acid change in the linear sequence is called

a mutation.

Q. Can you give an example? (Page 20)A. sickle cell anemia due to Haemoglobin S,

Q. What is the defect in HbS? (Page 20)A. Normally the 6th amino acid in the beta chain is

glutamic acid, this is replaced by valine in the HbSmolecule.


Q. Which are the forces that maintain the second-ary, tertiary and quaternary structures of a pro-tein? (Page 21)

A. Hydrogen bonds, Electrostatic bonds, Van derWaal�s forces and Hydrophobic bonds.

Q. What are the salient features of alpha structureof proteins? (Page 22)

A. It is a right-handed spiral structure; each turn isformed by 3.6 amino acid residues; it is majorstructural motif in globular proteins.

Q. Which will inhibit the formation of alpha helix?(Page 22)

A. Proline.

Q. What is meant by secondary structure of a pro-tein? (Page 22)

A. Secondary structure denotes the configurationalrelationship between residues which are about 3-4 amino acids apart. In other words, secondarylevel defines the organisation at immediate vicin-ity of amino acids.

Q. What is meant by tertiary structure of a protein?(Page 22)

A. The tertiary structure denotes three dimensionalstructure of the whole protein. It defines the stericrelationship of amino acids which are far apartfrom each other in the linear sequence.

Q. What is meant by a domain of a protein?(Page 22)

A. It is the term used to denote a compact unit of aprotein. It generally represents a functional unit.


Q. What is meant by quaternary structure of a pro-tein? (Page 22)

A. Certain polypeptides will aggregate to form onefunctional protein. This is referred to as the qua-ternary structure.

Q. Give some examples of proteins having quater-nary structure. (Page 23)

A. Hemoglobin, lactate dehydrogenase, immunoglo-bulin.

Q. What are the reagents that are used for identify-ing the first amino acid in a protein? (Page 24)

A. Fluoro dinitro benzene, dansyl chloride, phenyliso thio cyanate.

Q. Protein chains may be separated by what re-agent? (Page 24)

A. 8 molar urea.

Q. What is meant by Ingram�s technique?(Page 24)A. Protein digestion by trypsin, followed by two di-

mensional chromatography.

Q. It is otherwise known as what? (Page 24)A. Finger printing of proteins or peptide mapping.

Q. Secondary structure of protein can be studied bywhat methods? (Page 25)

A. X-ray diffraction study, optical rotatory disper-sion, and nuclear magnetic resonance (NMR).

Q. What is iso-electric point of a protein? (Page 25)A. At the iso-electric point, the number of anions and

cations present on the protein molecule will beequal and the net charge is zero.


Q. What are the characteristic features of iso-elec-tric point? (Page 25)

A. At the pI value, the proteins will not migrate inan electrical field; solubility, buffering capacityand viscosity will be minimum and precipitationwill be maximum.

Q. What is the iso-electric pH of human albumin?(Page 25)

A. It is 4.7.

Q. How proteins are precipitated from solution?(Page 25)

A. Any factor which neutralises the charge or re-moves water of hydration will cause precipita-tion of proteins.

Q. How albumin is precipitated? (Page 25)A. By full saturation of ammonium sulfate or 28 %

sodium sulfate.

Q. What will be precipitated by half-saturation ofammonium sulfate? (Page 25)

A. Globulins are precipitated by half-saturation ofammonium sulfate.

Q. Give an example of precipitation at iso-electricpoint. (Page 26)

A. Casein is precipitated when the solution isbrought to iso-electric pH.

Q. What is the iso-electric pH of casein? (Page 26)A. 4.6.


Q. Give some examples of anionic precipitatingagents. (Page 26)

A. Tungstic acid, phosphotungstic acid, trichloroacetic acid, picric acid, sulphosalicylic acid andtannic acid are protein precipitating agents.

Q. What are the features of denaturation?(Page 26)A. The secondary, tertiary and quaternary structures

are lost, but primary structure is preserved. Thefunctional activity is lost. The denature proteinsare insoluble and easily precipitated.

Q. What are the usual agents that cause denaturationof proteins? (Page 26)

A. Brief heating, urea, X-ray, ultraviolet ray, highpressure, vigorous shaking.

Q. What is heat coagulation? (Page 26)A. When heated at iso-electric point, some proteins

will denature irreversibly to produce thick float-ing conglomerates called coagulum. This is calledheat coagulation.

Q. Give examples of proteins that coagulate easily.(Page 26)

A. Albumin is easily coagulated, and globulins to alesser extent.

Q. How proteins are classified? (Page 27)A. They may be classified depending on the func-

tion or based on the physicochemical characteris-tics or based on their nutritional value.


Q. What is the functional classification of proteins?(Page 27)

A. 1. Catalytic proteins, 2. Structural proteins, 3. Con-tractile proteins, 4. Transport proteins, 5. Regula-tory proteins or hormones, 6. Genetic proteins,and 7. Protective proteins.

Q. Based on physiochemical properties, how arethey classified? (Page 27)

A. Simple proteins, conjugated proteins and derivedproteins.

Q. Give examples of simple proteins. (Page 27)A. Albumins, globulins, protamines, prolamines,

lectins, scleroproteins.

Q. Give examples of scleroproteins. (Page 27)A. Collagen of bone, cartilage and tendon, keratin of

hair, horn, nail and hoof.

Q. What are conjugated proteins? (Page 27)A. Combinations of protein with a non-protein part

is called prosthetic group.

Q. How are conjugated group subclassified?(Page 27)

A. Glycoproteins, lipoproteins, nucleoproteins, chro-moproteins, phospho-proteins and metallo-pro-teins.

Q. Give some examples of chromoproteins.(Page 27)

A. Hemoglobin, flavoproteins, visual purple.


Q. Give examples of phosphoproteins.(Page 27)

A. Casein of milk and vitellin of egg yolk.

Q. Where is this phosphate attached to proteins?(Page 27)

A. The phosphoric acid is added to the hydroxylgroups of serine and threonine residues of pro-teins.

Q. What are lectins? (Page 27)A. Plant proteins having specific carbohydrate bind-

ing site.

Q. Give an example of a nutritionally rich protein(first class protein). (Page 28)

A. Casein.

Q. Some proteins are called as poor proteins; why?(Page 28)

A. They lack in many essential amino acids and adiet based on these proteins will not even sustainthe body weight.

Q. Give an example of nutritionally poor protein.(Page 28)

A. Zein from corn lacks tryptophan and lysine.

Q. Which method of protein estimation is depen-dent on the intact peptide bond?

A. Biuret method. (Page 28)


Q. What is the advantage of biuret method?(Page 28)

A. The biuret method is simple one step process, andis the most widely used method for plasma pro-tein estimations.

Q. What is the disadvantage of biuret method?(Page 28)

A. The sensitivity of the method is less and is un-suitable for estimation of proteins in milligramor microgram quantities.

Q. What is the basis of Lowry�s method of proteinestimation? (Page 28)

A. This is based on the reduction of folin-ciocalteauphenol reagent (phosphomolybdic acid and phos-photungstic acid) by the tyrosine and tryptophanresidues of protein.

Q. Which component of the protein absorb UV lightat 280 nm? (Page 28)

A. Indole ring of tryptophan.

Q. What is nephelometry? (Page 29)A. Nephelometry is defined as the detection of light

scattered by turbid particles in solution.

Enzymology-I 27

Enzymology-I

Q. How are enzymes classified? (Page 30)A. They are classified into five major classes.

Q. What are those classes? (Page 30)A. Oxidoreductases, transferases, hydrolases, lyases,

isomerases and ligases.

Q. What is the function of oxidoreductases?(Page 30)

A. Transfer of hydrogen.

Q. Give an example of oxidoreducatase. (Page 30)A. Alcohol dehydrogenase.

Q. What is the function of transferases? (Page 31)A. Transfer of groups other than hydrogen.

Q. Give an example of transferase. (Page 31)A. Hexokinase.

Q. What is the function of hydrolases? (Page 31)A. Cleave bond after adding water.


Q. Give an example of a hydrolase. (Page 31)A. Acetyl choline esterase.

Q. Peptidases are classified under which class ofenzyme? (Page 31)

A. Hydrolases.

Q. What is the function of lyases? (Page 31)A. Cleave bond without adding water.

Q. Which enzyme will add water to a double bond,without breaking the bond?

A. Hydratase. (Page 31)

Q. Give an example of lyase. (Page 31)A. Aldolase.

Q. Give an example of isomerase. (Page 31)A. Triose phosphate isomerase.

Q. What is the function of ligases? (Page 31)A. ATP dependent condensation of two molecules.

Q. What is the difference between synthase and syn-thetase? (Page 31)

A. Synthetases are ATP-dependent enzymescatalysing biosynthetic reactions; they belong toLigases. Synthases are enzymes catalysing biosyn-thetic reactions; but they do not require ATP di-rectly; they belong to classes other than Ligases.

Q. Give examples of synthetases. (Page 31)A. Carbamoyl phosphate synthetase, arginino suc-

cinate synthetase, PRPP synthetase, glutaminesynthetase.

Enzymology-I 29

Q. Give examples of synthases. (Page 31)A. Glycogen synthase, ALA synthase, IMP synthase.

Q. What are co-enzymes? (Page 31)A. Enzyme may contain a non-protein part, the co-

enzyme. The co-enzyme is essential for the bio-logical activity of the enzyme. A co-enzyme is alow molecular weight organic substance, withoutwhich the enzyme cannot exhibit any reaction. Co-enzyme accepts one of the products of the reac-tion; and so act as a co-substrate.

Q. What is holo-enzyme? (Page 31)A. When apo-enzyme and co-enzymes are added,

holo-enzyme is produced. Fully active enzymeis called Holo-enzyme.

Q. How are co-enzymes classified? (Page 31)A. (a) Those taking part in reactions catalysed by oxi-

doreductases by donating or accepting hydrogenatoms or electrons. (b) Those co-enzymes takingpart in reactions transferring groups other thanhydrogen.

Q. Give some examples of co-enzymes involved inoxidoreductases. (Page 31)

A. NAD, NADP, FAD.

Q. What is the full form of NAD? (Page 32)A. Nicotinamide adenine dinucleotide.

Q. What is FAD? (Page 32)A. Flavin adenine dinucleotide.


Q. Give some examples of co-enzymes involved inreactions other than hydrogen transfer.

(Page 32)A. Thiamine pyrophosphate, pyridoxal phosphate,

biotin, co-enzyme A, ATP.

Q. What is the full form of ATP? (Page 32)A. Adenosine triphosphate.

Q. What is the function of ATP? (Page 32)A. It is the energy currency in the body. During the

oxidation of food stuffs, energy is released, a partof which is stored as chemical energy in the formof ATP. Other reaction requiring energy arecoupled with ATP.

Q. Name the enzymes containing copper.(Page 33)A. Superoxide dismutase, tyrosinase, cytochrome

oxidase.

Q. Which metal is required for the action of Kinases?(Page 33)

A. Magnesium.

Q. Chloride ions activate which enzyme? (Page 33)A. Amylase.

Q. Which enzyme contains molybdenum?(Page 33)

A. Xanthine oxidase.

Q. Name some iron containing enzymes. (Page 33)A. Cytochrome oxidase, catalase, peroxidase, xan-

thine oxidase.

Enzymology-I 31

Q. What is Michaelis-Menten Theory ? (Page 33)A. It is otherwise called enzyme-substrate complex

theory. The enzyme combines with the substrate,to form an enzyme-substrate complex, which im-mediately breaks down to the enzyme and theproduct.

Q. What is Fischer�s theory? (Page 34)A. It states that the three dimensional structure of

the active site of the enzyme is complementary tothe substrate. Thus, enzyme and substrate fit eachother like a key and its lock.

Q. What is Koshland�s induced fit theory?(Page 34)

A. The substrate induces conformational changes inthe enzyme, such that precise orientation of cata-lytic groups is effected.

Q. What is active site of an enzyme? (Page 35)A. That area of the enzyme where catalysis occurs is

referred to as active site or active center.

Q. What is meant by serine proteases? (Page 35)A. Proteases (proteolytic enzymes) having a serine

residue at its active center.

Q. Give an example of a serine protease. (Page 35)A. Trypsin, chymotrypsin, thrombin.

Q. Thermodynamically, how reactions are classi-fied? (Page 36)

A. Exothermic, isothermic and endothermic reac-tions.


Q. What is exothermic reaction? (Page 36)A. Here energy is released from the reaction, and

therefore reaction essentially goes to completion,e.g. urease enzyme, converting urea to ammonia+ CO2 + energy.

Q. What is endergonic reaction? (Page 36)A. Energy is consumed and external energy is to be

supplied for these reactions. In the body this isusually accomplished by coupling the endergonicreaction with an exergonic reaction, e.g. Hexoki-nase reaction, Glucose + ATP ® Glucose-6-Phos-phate + ADP.

Q. What are the salient features of enzyme kinet-ics? (Page 36)

A. Enzymes lower activation energy. They increasethe chemical reaction, but do not alter equilibriumof the reaction.

Q. What are the factors influencing enzyme reac-tion? (Page 36)

A. Enzyme concentration, substrate concentration,product concentration, temperature, pH and pres-ence of activators or inhibitors.

Q. What is Km value? (Page 37)A. Substrate concentration (expressed in moles/L)

at half-maximal velocity is the Km value.

Q. What does it indicate? (Page 37)A. It denotes that 50% of enzyme molecules are

bound with substrate molecules at that particu-lar substrate concentration

Enzymology-I 33

Q. What is its significance? (Page 37)A. Km is independent of enzyme concentration. Km

value is thus constant for an enzyme. It is the char-acteristic feature of a particular enzyme for a spe-cific substrate. Km denotes the affinity of enzymeto substrate. Thus, the lesser the numerical valueof Km, the affinity of the enzyme for the substrateis more.

Q. What is the use of assessing the Km value of anenzyme? What is the application? (Page 38)

A. Determination of Km value is also useful to un-derstand the natural substrate of an enzyme. Studyof Km value will also differentiate the competi-tive and non-competitive inhibitions.

Q. What is the effect of temperature on enzyme ve-locity? (Page 39)

A. The velocity of reaction increases when tempera-ture is increased, reaches a maximum and thenfalls (Bell-shaped curve)

Q. Why it falls? (Page 39)A. when temperature is more than 50ºC, heat dena-

turation and consequent loss of tertiary structureof protein occurs.

Q. What is the effect of pH on the activity of an en-zyme? (Page 39)

A. Each enzyme has an optimum pH, on both sidesof which the velocity will be drastically reduced.The graph will show a bell-shaped curve.


Q. What is the explanation for the effect of pH?(Page 39)

A. The pH decides the charge on the amino acid resi-dues at the active site. The net charge on the en-zyme protein would influence substrate bindingand catalytic activity.

Q. What is the optimum pH of usual enzymes?(Page 39)

A. Usually enzymes have the optimum pH between6 and 8.

Q. Are there any important exceptions for this gen-eral rule? (Page 39)

A. Pepsin (optimum pH 1-2), alkaline phosphatase(optimum pH 9-10) and Acid phosphatase (4-5).

Q. What is zymogen? (Page 39)A. It is otherwise called pro-enzyme. Inactive zy-

mogen is activated by removal of a piece of thepro-enzyme.

Q. Give an example of zymogen is activated?(Page 39)

A. By splitting a single peptide bond, and removalof a small polypeptide from trypsinogen, the ac-tive trypsin is formed. This results in unmaskingof the active centre.

Enzymology-I 35

Q. What is the significance of zymogen activation?(Page 39)

A. Gastro-intestinal enzymes are synthesised in theform of pro-enzymes, and only after secretion intothe alimentary canal, they are activated. This pre-vents autolysis of cellular structural proteins. Co-agulation factors are seen in blood as zymogenform, their activation takes place only when ne-cessity arises. This prevents intravascular coagu-lation.

Q. What are the different types of inhibitions ofenzyme activity? (Page 39)

A. Competitive inhibition, non-competitive inhibi-tion, suicide inhibition, and allosteric regulation.

Q. What are salient features of competitive inhibi-tion? (Page 40)

A. Competitive inhibitor is a structural analogue. 2.It is reversible. 3. Km is increased. 4. Vmax is notchanged.

Q. Give examples of competitive inhibition.(Page 40)

A. Malonate inhibits succinate dehydrogenase.

Q. Give examples of clinical application of competi-tive inhibition. (Page 40)

A. Sulfonamide inhibits PABA incorporation in bac-teria, and so acts as an antibacterial agent. Meth-otrexate inhibits folate reductase system,dicoumarol inhibits vitamin K.


Q. What is the immediate treatment for methanolpoisoning? (Page 41)

A. Methanol is oxidised by alcohol dehydrogenaseto formaldehyde which causes the acute toxicity.Antidote to methanol poisoning is ethanol whichis the natural substrate for alcohol dehydrogenase.So ethanol is preferentially utilised.

Q. What are the salient features of non-competitiveinhibition? (Page 41)

A. Non-competitive inhibitor has no structural simi-larity with the substrate. 2. It is generally not re-versible 3. Km is not changed. 4. Vmax is reduced.

Q. Give examples of non-competitive inhibition.(Page 41)

A. Di-isopropyl fluoro phosphate inhibits trypsin,fluoride inhibits and enolase.

Q. Iodo-acetate inhibits enzyme by reacting withwhich group at the active site of the enzyme?

(Page 41)A. Sulfhydryl group.

Q. What is the mechanism of inhibitory action ofDi-isopropyl fluoro phosphate? (Page 41)

A. It inhibits enzymes with serine in their active cen-tres, e.g. acetylcholine esterase.

Q. What is suicide inhibition? (Page 42)A. In suicide inhibition, the structural analogue is

converted to a more effective inhibitor with thehelp of the enzyme to be inhibited. The inhibitormakes use of the enzyme�s own reaction mecha-nism to inactivate it.

Enzymology-I 37

Q. What is the other term for suicide inhibition?(Page 42)

A. Mechanism based inactivation.

Q. Give examples for suicide inhibition. (Page 42)A. Ornithine decarboxylase (ODC) is inhibited by

difluro methyl ornithine (DFMO). Another ex-ample is Allopurinol which is oxidised by xan-thine oxidase to alloxanthine that is a strong in-hibitor of xanthine oxidase.

Q. What is allosteric inhibition? (Page 42)A. Allosteric enzyme has one catalytic site where the

substrate binds and another separate allostericsite where the modifier binds.

Q. What are the salient features of allosteric inhibi-tion? (Page 43)

A. (1) The inhibitor is not a substrate analogue. (2) Itis partially reversible when excess substrate isadded. (3) Km is usually increased. (4) Vmax isreduced. (5) Most allosteric enzymes possess qua-ternary structure. They are made up of subunits.

Q. Give examples for allosteric inhibition.(Table 5.7)

A. ALA synthase, aspartyl trans-carbamoylase,HMG CoA reductase

Q. What is covalent modification? (Page 43)A. It means, either addition of a group to the enzyme

protein by a covalent bond; or removal of a groupby cleaving a covalent bond.


Q. Give some examples of covalent modification.(Page 44)

A. Glycogen synthase is inactive, in the phosphory-lated state, whereas glycogen phosphorylase isactive when phosphorylated.

Q. What is meant by induction? (Page 44)A. Induction is effected at the level of DNA. The in-

ducer will relieve the repression on the operatorsite and will remove the block on the biosynthe-sis of the enzyme molecules.

Q. Give an example of induction. (Page 44)A. Induction of lactose-utilising enzymes in the bac-

teria when the media contains lactose in the ab-sence of glucose. In humans, Tryptophanpyrrolase and transaminases are induced by glu-cocorticoids. Glucokinase is induced by glucose.ALA synthase is induced by barbiturates.

Q. What are constitutive enzymes? (Page 44)A. Enzymes whose concentration in a cell is inde-

pendent of inducer are called constitutive en-zymes.

Q. What is repression? (Page 44)A. Repression acts at the gene level, the number of

enzyme molecules is reduced in the presence ofrepressor molecule.

Q. Give an example of repression. (Page 44)A. The key enzyme of heme synthesis, ALA synthase

is autoregulated by the heme by means of repres-sion.

Enzymology-I 39

Q. Give examples of multi-enzyme complexes.(Page 44)

A. Fatty acid synthase, pyruvate dehydrogenase, andalpha keto glutarate dehydrogenase.

Q. What are the types of specificity shown by en-zymes? (Page 45)

A. Absolute specificity, group specificity andstreospecificity.

Q. Give an example for absolute specificity.(Page 45)

A. Urea is the only substrate for urease.

Q. Give an example for group specificity. (Page 45)A. trypsin can hydrolyse peptide bonds formed by

carboxyl groups of arginine or lysine residues.


Q. What are iso-enzymes? (Page 46)A. They are physically distinct forms of the same

enzyme activity. They have identical catalyticproperties, but differ in structure.

Q. How to differentiate iso-enzymes. (Page 46)A. Electrophoresis, heat stability, km value, inhibi-

tor specificity, and tissue localization.

Q. Which is a functional enzyme in plasma?(Page 46)

A. They are actively secreted into plasma, and havesome functions in the blood. For example, en-zymes of blood coagulation.

Q. What is non-functional enzymes in plasma?(Page 46)

A. They are coming out from cells due to normalwear and tear.

Enzymology-IIIso-Enzymes andClinical Enzymology

Enzymology-II 41

Q. What is their clinical significance? (Page 46)A. Their normal levels in blood are very low, but

are drastically increased during cell death (necro-sis) or disease. Therefore, assays of these enzymesare very useful in diagnosis of diseases.

Q. Lactate dehydrogenase has how many polypep-tide subunits? (Page 47)

A. Four. It is a tetramer.

Q. Lactate dehydrogenase has how many iso-en-zymes? (Page 47)

A. Five

Q. What are they? (Page 47)A. H4, H3M, H2M2, M3H and M4 varieties, forming

five iso-enzymes. All these five forms are seen inall persons.

Q. How do you separate LDH iso-enzymes in labo-ratory? (Page 47)

A. By cellulose acetate electrophoresis at pH 8.6.

Q. LDH level in blood is increased in which condi-tions? (Page 47)

A. Myocardial infarction, hemolytic anemias, mus-cular dystrophy, carcinomas, leukemias, and anycondition which causes necrosis of body cells.

Q. How do you further investigate for myocardialinfarction? (Page 47)

A. LDH-1 (H4) iso-enzyme is increased.


Q. What is flipped pattern? (Page 47)A. Normally LDH-2 (H3M1) concentration in blood

is greater than LDH-1 (H4), but this pattern is re-versed in myocardial infarction, this is calledflipped pattern.

Q. What are the serum enzymes helpful in the di-agnosis of myocardial infarction?

A. Lactate dehydrogenase (LDH) H4 iso-enzyme,creatine kinase (CK) CK MB iso-enzyme and as-partyl transaminase (AST).

Q. Creatine kinase (CK) level in serum is increasedin which conditions?

A. Myocardial infarction, muscular dystrophies.(Page 48)

Q. What is the advantage of CK estimation overLDH estimation to identify myocardial infarc-tion? (Page 48)

A. The CK level starts to rise within three hours ofinfarction. Therefore, CK estimation is very use-ful to detect early cases, where ECG changes maybe ambiguous. The CK level is not increased inhemolysis or in congestive cardiac failure; andtherefore CK has an advantage over LDH.

Q. What are the iso-enzymes of CK? (Page 48)A. CK is a dimer, the subunits are called B for brain

and M for muscle. Therefore, three iso-enzymesare possible.

Enzymology-II 43

Q. What are the origins of the CK iso-enzymes?(Page 48)

A. Eighty percent of molecules in circulation are MM(CK3) variety of skeletal origin, five percent incirculation are MB (CK2) from heart, one percentfrom brain (BB or CK1) and fifteen percent CKmtfrom mitochondria.

Q. When do you estimate total CK and the iso-en-zyme? (Page 48)

A. Estimation of total CK is employed in musculardystrophies and CK-MB iso-enzyme is estimatedto identify myocardial infarction.

Q. What is the advantage of cardiac troponin I overother parameters to identify the myocardial inf-arction? (Page 48)

A. Cardiac Troponin I is released into the bloodwithin four hours after the onset of cardiac symp-toms, peaks at 12-16 hours and remains elevatedfor 5-9 days post-infarction. Therefore, CTI is veryuseful as a marker at any time interval after theheart attack. It is 75% sensitive index for myocar-dial infarction.

Q. What is the significance of AST? (Page 48)A. It is significantly elevated in myocardial infarc-

tion and moderately elevated in liver diseases.

Q. What is the significance of ALT? (Page 49)A. Very high values are seen in acute hepatitis. Rise

in ALT levels may be noticed several days beforeclinical signs such as jaundice are manifested.Moderate increase may be seen in chronic liverdiseases such as cirrhosis, and malignancy in liver.


Q. Alkaline phosphatase level in serum is elevatedin which conditions? (Page 49)

A. Moderate increase is seen in hepatic diseases (in-fective hepatitis, alcoholic hepatitis). High levelsmay be noticed in obstructive jaundice orcholestasis. Very high levels are seen in bone dis-eases such as Paget�s disease, rickets, osteomala-cia, osteoblastoma, metastatic carcinoma of bone.

Q. For alkaline phosphatase, how many iso-en-zymes are present? (Page 49)

A. Six.

Q. What is Regan iso-enzyme? (Page 49)A. It is the iso-enzyme of alkaline phosphatase, in-

hibited by phenylalanine. It is of placental origin.It is elevated in about 15% cases of carcinoma oflung, liver and gut and then named as Regan iso-enzyme or carcinoplacental iso-enzyme.

Q. It is said that nucleotide phosphatase (NTP) is abetter index of obstructive liver disease than al-kaline phosphatase (ALP), why? (Page 49)

A. ALP level is increased in both liver and bone dis-eases, but NTP is only in liver diseases.

Q. Estimation of gamma glutamyl transferase is use-ful to detect which condition? (Page 50)

A. Alcohol abuse.

Q. What are the enzymes useful in diagnosing liverpathology? (Page 50)

A. ALT, ALP, GGT, NTP.

Enzymology-II 45

Q. Give the clinical implications of these enzymes.(Page 50)

A. In infective hepatitis, ALT level is increased; inalcohol abuse, GGT level is increased; in obstruc-tive jaundice, ALP level is increased.

Q. Serum acid phosphatase level is increased inwhich condition? (Page 50)

A. Prostate carcinoma.

Q. Total acid phosphatase may increase in someother conditions also; what are they? (Page 50)

A. Prostate carcinoma, secondary metastasis inbones, per rectal examination, intravascularhemolysis.

Q. In such conditions, iso-enzyme study is helpfulor not? (Page 50)

A. Yes, tartarate labile iso-enzyme is specific for pros-tate carcinoma.

Q. What is the advantage of prostate specific anti-gen? (Page 50)

A. PSA is very specific for prostate carcinoma.

Q. What are the enzymes useful as tumour mark-ers? (Page 50)

A. Regan iso-enzyme of ALP for lung tumour;tartarate labile iso-enzyme of ACP and Prostatespecific antigen (PSA) for prostate carcinoma;Neuron specific enolase (NSE) for cancers ofneuro-endocrine origin.


Q. Pseudo-cholinesterase deficiency is manifestedas what? (Page 50)

A. Succinyl choline apnoea; prolonged apnea whensuccinyl choline is given as anesthetic drug.

Q. Which enzyme deficiency is inherited as X-linked? (Page 50)

A. Glucose-6-phosphate-dehydrogenase.

Q. How the deficiency of GPD is manifested?(Page 51)

A. Drug induced hemolytic anemia.

Q. Acute pancreatitis can be diagnosed by estimat-ing which enzymes? (Page 51)

A. Amylase and lipase.

Q. Name some enzymes that are used as therapeu-tic agents. (Page 52)

A. Asparaginase for leukemia, streptokinase to dis-solve clots, and pepsin for indigestion.

Methods of Separation & Purification of BiologicalCompounds, Methods of Study of Metabolism 47

Q. What is meant by electrophoresis? (Page 53)A. The term refers to the movement of charged par-

ticles through an electrolyte when subjected to anelectric field.

Q. What are the factors affecting the mobility in elec-trophoresis? (Page 53)

A. Net charge on the particles (pI of proteins), massand shape of the particles, the pH of the medium,strength of electrical field, and properties of thesupporting medium.

Q. What are the types of electrophoresis? (Page 53)A. Horizontal and vertical types.

Q. What are the supporting media used? (Page 53)A. Filter paper, cellulose acetate, agar gel, agarose

gel, starch gel and polyacrylamide gel.

Methods of Separationand Purification ofBiological Compounds,Methods of Study ofMetabolism


Q. Electrophoresis is commonly employed for whatpurpose in laboratory?

A. For serum electrophoresis and to see abnormali-ties in serum protein concentrations.

Q. What is the advantage of polyacrylamide gel?(Page 53)

A. It has a molecular sieving effect and so separa-tion is very efficient.

Q. What is immuno-electrophoresis? (Page 54)A. Here electrophoretic separation is followed by an

antigen-antibody reaction.

Q. What is the principle of adsorption chromatog-raphy? (Page 54)

A. separation is based on differences in adsorptionat the surface of a solid stationary medium.

Q. What is the principle of partition chromatogra-phy? (Page 55)

A. the components of the mixture to be separatedare partitioned between the two phases depend-ing on the partition co-efficient (solubility) of theparticular substances.

Q. What are the common types of partition chroma-tography? (Page 55)

A. Paper chromatography and thin layer chromatog-raphy.

Q. What is the advantage of TLC over paper chro-matography? (Page 55)

A. TLC needs lesser time, and separation is more ef-fective.


Q. What is Rf value? (Page 56)A. It is the ratio of the distance travelled by the sub-

stance (solute) to the distance travelled by the sol-vent. The Rf value is a constant for a particularsolvent system at a given temperature.

Q. What is the basic principle of ion-exchange chro-matography? (Page 56)

A. Here, the separation is based on electrostatic at-traction between charged molecules to oppositelycharged groups on the ion exchange resins.

Q. What is the principle of gel filtration chromatog-raphy? (Page 56)

A. The separation is effected on the basis of the sizeof the molecules. It is otherwise called molecularsieving.

Q. Give the principle of affinity chromatography.(Page 56)

A. The technique is based on the high affinity of spe-cific proteins for specific chemical groups.

Q. Give an example of affinity chromatography.(Page 57)

A. Separation and quantitation of glycated hemoglo-bin.

Q. What is the quickest method for separation ofproteins? (Page 58)

A. HPLC.


Q. What is the principle of ultracentrifugation?(Page 58)

A. Large molecules can be sedimented at high cen-trifugal forces whereas small molecules cannot.Rate of sedimentation depends on the size, shapeand density of solute particles.

Q. What is Svedberg unit? (Page 57)A. Sedimentation constant is expressed in Svedberg

(S) units.

Q. What are the uses of ultracentrifugation?

A. 1. Separation of subcellular organelles. 2. Separa-tion of lipoproteins. 3. Determination of molecu-lar weight of proteins.

Q. What are the methods used to determine themolecular weight of proteins?

A. (1) Ultracentrifugation, (2) Gel filtration and (c)PAGE (poly acrylamide gel electrophoresis).

(Page 57)

Q. What is the advantage of radio-immuno assay?(Page 57)

A. Very small quantities of substances could be ac-curately measured.

Q. What is the radio-active label used for RIA?(Page 58)

A. Iodine-125.

Q. What is the half life of Iodine-125? (Page 58)A. About 60 days.


Q. What are the disadvantages of RIA, when com-pared to ELISA? (Page 58)

A. 1. Since radio-isotopes are used, only approvedlaboratories could take up the assay. 2. The shelflife of the reagent is short.

Q. What are the enzymes commonly used in ELISAtechnique. (Page 58)

A. Alkaline phosphatase (ALP) and horse radish per-oxidase (HRP).


Q. How carbohydrates are classified? (Page 61)A. Based on the number of the sugar units available,

they are classified as monosaccharides, disaccha-rides, oligosaccharides, and polysaccharides.

Q. What is a monosaccharide? (Page 61)A. Molecules having only one actual or potential

sugar group are called monosaccharides.

Q. What is a polysaccharide? (Page 61)A. They contain more than 10 sugar units.

Q. How are they combined together? (Page 61)A. Through glycosidic linkages.

Q. How are monosaccharides further classified?(Page 61)

A. Sugars having aldehyde group are called aldosesand sugars with keto group are ketoses.

Carbohydrates-I:Chemistry, Digestionand Absorption

Carbohydrates-I 53

Q. Name some important monosaccharides.(Page 61)

A. Glucose, fructose, galactose, mannose.

Q. What are pentoses? (Page 61)A. Monosaccharides with five carbon atoms.

Q. Name a few pentoses. (Page 61)A. Arabinose, Xylose, Ribose.

Q. Which is the reference carbon atom in sugars?(Page 62)

A. Penultimate carbon atom.

Q. What is the difference between D and L sugars?(Page 62)

A. They are mirror images with reference topenultimate carbon atom.

Q. Which isomer is common in nature? (Page 62)A. D variety of sugars are common in nature.

Q. Which is the most common monosaccharide inthe body?

A. Glucose. (Page 62)

Q. What is the difference between glucose and ga-lactose? (Page 62)

A. They are different with regard to the H and OHgroups at the 4th carbon atom. Galactose is the4th epimer of glucose (Fig.8.3).

Q. Galactose is present in which food? (Page 62)A. Lactose is present in milk. Lactose contains ga-

lactose and glucose.


Q. What is epimerism? (Page 62)A. When sugars are different from one another, only

in configuration with regard to a single carbonatom (other than the reference carbon atom), theyare called epimers.

Q. Give an example. (Page 62)A. For example, glucose and mannose are an

epimeric pair which differ only with respect tocarbon atom 2. Similarly, galactose is the 4thepimer of glucose. (Fig. 8.3).

Q. Anomerism is produced with reference withwhich carbon atom? (Page 62)

A. Anomers are produced by the spatial configura-tion with reference to the first carbon atom in al-doses and second carbon atom in ketoses. (Fig.8.4).

Q. How alpha and beta forms of sugars are pro-duced? (Page 62)

A. These are anomers. The difference lies in the spa-tial configuration with reference to the first car-bon atom in aldoses and second carbon atom inketoses. (Fig. 8.4).

Q. What is the basis of mutarotation? (Page 62)A. It is due to the anomeric carbon atom.

Q. What is the difference between glucose and fruc-tose?

A. Glucose is an aldohexose, and fructose is aketohexose.

Carbohydrates-I 55

Q. Name a ketose. (Page 63)A. Fructose.

Q. What is the principle of Benedict�s test?(Page 64)

A. In alkaline medium, sugar will cause reductionof cupric ions, to form red coloured precipitate.

Q. What is the composition of Benedict�s reagent.(Page 64)

A. It contains sodium carbonate, copper sulfate andsodium citrate. In the alkaline medium providedby sodium carbonate, the copper remains as cu-pric hydroxide. Sodium citrate acts as a stabilisingagent to prevent precipitation of cupric hydrox-ide.

Q. Benedict�s test is commonly employed for what?(Page 64)

A. To detect the presence of glucose in urine.

Q. Name a few reducing sugars. (Page 64)A. Glucose, fructose, mannose.

Q. Keto group is non-reducing, but fructose reducesBenedict�s solution, what is the cause for thisanomaly? (Fig. 8.10)

A. In alkaline medium, ketone group is convertedto aldehyde, through enediol formation.

Q. In the case of sugars, which of the properties gohand in hand?

A. Reducing property, osazone formation and mu-tarotation. (page 64)


Q. Glucose and fructose will form identicalosazones, why?

A. The difference in glucose and fructose is depen-dent on the first and second carbon atoms, andthis is masked by the osazone formation.

(Page 64)

Q. On oxidation of glucose, what are produced?(Page 64)

A. Glucuronic acid, gluconic acid and glucos-accharic acid.

Q. Reduction of glucose produces what? (Page 64)A. Sorbitol.

Q. Name some deoxy sugars. (Page 66)A. Deoxy ribose, fucose (deoxy galactose).

Q. Which is the stain used to identify deoxysugar?(Page 66)

A. Feulgen staining.

Q. Name some important disaccharides. (Page 67)A. Sucrose, lactose, maltose.

Q. What is the glycosidic linkage in lactose?(Page 67)

A. Beta 1-4 linkage.

Q. What is the glycosidic linkage in sucrose?(Page 67)

A. 1-2 linkage.

Carbohydrates-I 57

Q. Which disaccharide has no free aldehyde or ke-tone group?

A. Sucrose. (Page 67)

Q. Glucose and fructose are reducing sugars, butsucrose (containing glucose and fructose) is anon-reducing sugar, why? (Page 67)

A. Because the glycosidic linkage in sucrose involves1st carbon of glucose and 2nd carbon of fructose,so both reducing groups are masked.

Q. Hydrolysis of maltose will give rise to what ?(Page 67)

A. Two glucose units.

Q. Which is the sugar found in milk? (Page 67)A. Lactose.

Q. What are the component monosaccharides of lac-tose? (Page 67)

A. Galactose and glucose.

Q. Sucrose consists of what monosaccharides?(Page 67)

A. Glucose + fructose.

Q. Name reducing disaccharides. (Page 67)A. Lactose and maltose.

Q. How polysaccharides are classified? (Page 68)A. Homopolysaccharides (homoglycans) and

heteropolysaccharides (heteroglycans).

Q. What is a homopolysaccharide? (Page 68)A. They are composed of single kind of monosac-

charides.


Q. Give examples of homopolysaccharides.(Page 68)

A. Starch, and glycogen.

Q. What are heteropolysaccharides? (Page 68)A. They are composed of two or more different

monosaccharides.

Q. What are the characteristics of glycogen?(Page 69)

A. It is composed of glucose units. It is the storedform of carbohydrate in animal kingdom. It has ahighly branched structure.

Q. What is the reserve carbohydrate in plant king-dom? (Page 69)

A. Starch.

Q. What is the end product of action of pancreaticamylase on starch? (Page 69)

A. Maltose.

Q. Cellulose and starch are polysaccharides madeof glucose, but cellulose cannot be digest byhuman beings, why? (Page 69)

A. Cellulose contains beta 1,4 linkages, which can-not be digested by human enzymes.

Q. What is inulin? (Page 69)A. It is a homopolysaccharide, composed of fructose

units.

Q. What is the use of inulin? (Page 69)A. It is used to find renal clearance and glomerular

filtration rate.

Carbohydrates-I 59

Q. Give examples of heteropolysaccharides.(Page 70)

A. Agar, hyaluronic acid, heparin, chondroitin sul-fate.

Q. What are mucopolysaccharides? (Page 70)A. They contain uronic acid and amino sugars.

Q. Which heteropolysaccharide does not containuronic acid? (Page 70)

A. Keratan sulfate.

Q. Hyaluronic acid is seen in which tissues?(Page 70)

A. Connective tissue, synovial fluid, tendons, vitre-ous humor.

Q. What is the difference between glycoprotein andmucoprotein? (Page 71)

A. If the carbohydrate content is less than 10%, it iscalled a glycoprotein. If the carbohydrate contentis more than 10% it is a mucoprotein.

Q. The rate of absorption of sugars in intestine ishighest for which monosaccharide? (Page 71)

A. Absorption rate of galactose is more than glucose,while fructose is absorbed at a lesser rate thanglucose.

Q. Glucose is absorbed at the luminal side of gastrointestinal cells by which mechanism?

(Page 72, and Fig. 8.30)A. Carrier mediated co-transport with sodium,

named as sodium dependent glucose transporter(SGluT).


Q. How glucose is released from intestinal cells intothe blood stream?

A. Glucose transporter type 2 (GluT2) (Fig.8.30).

Q. How glucose is taken up by cells from bloodstream? (Page 72)

A. In tissues GluT2 is involved in absorption of glu-cose from blood.

Q. What is the importance of GluT4? (Page 72)A. It is the glucose transporter present in muscle and

adipose tissues. Insulin induces these transport-ers. In diabetes mellitus, entry of glucose intomuscle is decreased, because GluT4 is reducedin insulin deficiency.

Q. What is the glucose sensor in the beta cells ofpancreas? (Page 72)

A. GluT2 acts as the glucose sensor mechanism, forthe controlled supply of insulin into blood stream.

Carbohydrates-II 61

Carbohydrates-II:Major MetabolicPathways of Glucose,Glycolysis, Gluconeogenesis,Glycogen Metabolism

Q. What is glycolysis? (Page 73)A. In this pathway, glucose is converted to pyruvate

or lactate, along with production of a small quan-tity of energy.

Q. In which condition pyruvate is produced, andwhen lactate? (Page 73)

A. In aerobic condition pyruvate is produced. Whenoxygen is lacking, lactate is produced.

Q. What is the significance of Glycolysis?(Page 73)A. It is the only pathway that is taking place in all

the cells of the body. Glycolysis is the only sourceof energy in erythrocytes. Moreover, anaerobicglycolysis forms the major source of energy inactively contracting muscles.


Q. What is hexokinase? (Page 73)A. Hexokinase is the first step in the glycolysis path-

way. It phosphorylates glucose to glucose-6-phos-phate.

Q. What is glucokinase? (Page 73)A. The reaction is similar to hexokinase. But glucoki-

nase is present only in liver, acts specifically onglucose, and is active when glucose level in bloodis increased after a food.

Q. Which tissues prefer anaerobic glycolysis?(Page 73)

A. RBCs, exercising muscle, and cancer cells.

Q. What is the importance of phospho fructokinase?(Page 74)

A. It is the key enzyme (rate limiting enzyme) of thepathway. It is an irreversible reaction.

Q. What is the substrate for aldolase reaction?(Page 74)

A. Fructose-1,6-bisphosphate.

Q. During glycolysis, energy is produced duringwhich steps? (Page 74, 75)

A. Step 5, glyceraldehyde-3-phosphate to 1,3-bisphospho glycerate, Step 6, 1,3-bis phosphoglycerate to 3-phospho glycerate, and Step 9,Phospho enol pyruvate to pyruvate.

Q. Fluoride ions inhibit which enzyme? (Page 75)A. Enolase.

Carbohydrates-II 63

Q. What is the importance of the above inhibition?(Page 75)

A. Fluoride is used to prevent glycolysis, as preser-vative for blood before glucose estimation.

Q. NAD is reduced to NADH in which reaction ofglycolysis? (Page 75)

A. Glyceraldehyde-3-phosphate dehydrogenase re-action.

Q. NADH is oxidised to NAD in which reaction ofglycolysis? (Page 76)

A. Lactate dehydrogenase reaction.

Q. What are substrate level phosphorylations in gly-colysis? (Page 75, 76)

A. 1,3-bisphospho glycerate kinase (step 6) and pyru-vate kinase (step 9).

Q. What is the purpose of lactic acid productionunder anaerobic conditions?

A. NADH generated in the 5th step has to beoxidised to NAD+. This can be done by oxygen.But when oxygen is lacking, the 5th step has to becoupled with the 10th step for regeneration ofNAD.

(See Fig. 9.11)

Q. As the end product of glycolysis, pyruvate andNADH are formed. During anaerobiasis, thisNADH is reconverted to NAD+ by what mecha-nism? (Page 76)

A. Lactate dehydrogenase reaction.


Q. As the end product of glycolysis, pyruvate andNADH are formed. During aerobic conditions,this NADH is reconverted to NAD+ by whatmechanism? (Page 76)

A. Oxygen.

Q. What is Cori�s cycle? (Fig.9.13)A. During exercise, lactate is produced in muscle.

This lactate diffuses into the blood. Lactate thenreaches liver, where it is oxidised to pyruvate. Itis then taken up through gluconeogenesis path-way, and becomes glucose. This glucose can en-ter into blood and then taken to muscle. This cycleis called Cori�s cycle, or lactic acid cycle.

Q. What is the purpose of Cori�s cycle? (Page 77)A. By this means, the lactate is efficiently reutilised

by the body.

Q. Why lactate is transported from muscle to liver?(Page 77)

A. Oxygen is limited in muscle, so lactic acid couldnot be made to pyruvate in muscle. So, it is trans-ported to liver, where it is made to pyruvate andthen to glucose.

Q. What are the inhibitors of phosphofructokinase?(Page 77)

A. ATP, Citrate, Glucocorticoids.

Q. What are the activators of phospho fructo kinase?(Page 77, 78)

A. AMP, Fructose-2,6-bisphosphate, Fructose-6-phosphate.

Carbohydrates-II 65

Q. What are key glycolytic enzymes? (Page 77, 78)A. Glucokinase, Phospho fructo kinase, Pyruvate ki-

nase.

Q. What is the action of insulin on glycolysis?(Page 77, 78)

A. Insulin stimulates glycolysis.

Q. What is the net yield of ATP from one glucosemolecule during anaerobic glycolysis?

(Page 78 and Table 9.3)A. 2 ATP.

Q. In aerobic glycolysis, the net yield from one glu-cose molecule is how much?


Q. During complete oxidation, what is the net yieldof ATP from one glucose molecule?


Q. How many ATPs are generated per one rotationof the citric acid cycle?

A. 12 ATP.

Q. What is the function of 2,3-bisphospho glycerate?(Page 79)

A. When combined with hemoglobin, 2,3-BPG re-duces the affinity towards oxygen.

Q. What are the steps in which carbon dioxide isproduced from a glucose molecule? (Page 80)

A. Pyruvate dehydrogenase, isocitrate dehydroge-nase, alpha keto glutarate dehydrogenase.


Q. What are the co-enzymes necessary for oxidativedecarboxylation of pyruvate? (Page 80)

A. Thiamine pyrophosphate, NAD, FAD, Lipoic acid,Co-enzyme A.

Q. What is pyruvate dehydrogenase? (Fig. 9.19)A. The enzyme catalysing the reaction, pyruvate to

acetyl CoA.

Q. What is pyruvate carboxylase? (Fig. 9.20)A. The enzyme catalysing the reaction, pyruvate to

oxaloacetate.

Q. What is pyruvate kinase? (Fig. 9.20)A. It catalyses the reaction, phospho enol pyruvate

to pyruvate.

Q. There is no net synthesis of glucose from fattyacids, why? (Page 80)

A. Pyruvate to acetyl CoA is a totally irreversiblereaction.

Q. Which enzyme irreversibly channels glucose toenergy production, rather than retaining glucosefor blood sugar regulation? (Page 80)

A. Pyruvate dehydrogenase is an irreversible reac-tion.

Q. Pyruvate is converted to acetyl CoA by whichenzyme? (Page 80)

A. Pyruvate dehydrogenate.

Q. What is gluconeogenesis? (Page 81)A. Production of glucose from non-carbohydrate

sources.

Carbohydrates-II 67

Q. What are those non-carbohydrate sources? (Whatare the substrates for gluconeogenesis?).

(Page 82, 83)A. Glucogenic amino acids and lactate.

Q. What are the key gluconeogenic enzymes?(Page 82)

A. Pyruvate carboxylase, Phospho enol pyruvatecarboxy kinase, Fructose-1,6-bisphosphatase andGlucose-6-phosphatase.

Q. Pyruvate carboxylase reaction (pyruvate to ox-aloacetate) needs which co-enzyme? (Page 81)

A. Biotin and ATP.

Q. Malate shuttle is used for what purpose?(Page 82)

A. Reactions of gluconeogenesis are taking place incytosol. Hence the oxaloacetate has to be trans-ported from mitochondria to cytosol. This isachieved by the malate shuttle (see Fig. 9.22).

Q. Gluconeogenesis is taking place in which tissue?(Page 81)

A. Liver.

Q. How many ATP molecules are required to con-vert two molecules of pyruvate into glucose?

(Page 82)A. Six.

Q. Blood glucose level can be raised by gluconeo-genesis only by liver, why? (Page 82)

A. Glucose-6-phosphatase is present only in liver.


Q. Muscle glycogen will not serve as a precursor ofblood sugar, why? (Page 82)

A. Glucose-6-phosphatase is absent in muscle.

Q. Which amino acids are both ketogenic and gluco-genic? (Fig. 9.29)

A. Tyrosine and tryptophan.

Q. What will inhibit gluconeogenesis? (Page 85)A. Insulin.

Q. What will stimulate gluconeogenesis? (Page 85)A. Glucagon and glucocorticoids.

Q. What is the significance of gluconeogenesis?(Page 85)

A. Gluconeogenesis is necessary to maintain bloodglucose level especially under conditions of star-vation.

Q. What is glycogenolysis? (Page 86)A. Degradation of glycogen to glucose.

Q. What is the main enzyme for glycogenolysis?(Page 86)

A. Glycogen phosphorylase.

Q. Which hormones enhance glycogenolysis?(Page 87)

A. Adrenaline and glucagon causes glycogenolysis.

Q. What is the mechanism of action of adrenaline?(Page 87)

A. Adrenaline increases cyclic AMP level which ac-tivates glycogen phosphorylase.

Carbohydrates-II 69

Q. In the glycogen synthesis, which is the activeglucose derivative?

A. UDP-glucose.

Q. Adrenaline acts on which enzyme?

A. Glycogen phosphorylase.

Q. What will activate glycogen phosphorylase?(Page 87)

A. Epinephrine, glucagon, cyclic AMP.

Q. Which is the defective enzyme in von Gierke�sdisease (glycogen storage disease type I)?

(Page 89)A. Glucose-6-phosphatase.

Q. What are the characteristic clinical features of vonGierke�s disease?

A. Fasting hypoglycemia, which does not respondto adrenaline is very characteristic. (Page 89)


Q. What is the level of fasting blood sugar in a nor-mal person?

A. 70-110 mg/dl. (Page 90)

Q. Which hormone is hypoglycemic? (Page 90)A. Insulin.

Q. What are the major actions of insulin? (Page 90)A. Insulin decreases blood sugar, it stimulates gly-

colysis, inhibits gluconeogenesis, enhances glyco-gen synthesis and inhibits lipolysis.

Q. What are the anti-insulin (hyperglycemic) hor-mones? (Page 90)

A. Glucagon, adrenaline, corticosteroids, growthhormone.

Q. What are the major actions of glucagon?(Page 91)

A. Promotes glycogenolysis, enhances gluconeogen-esis, depresses glycogen synthesis, inhibits gly-colysis.

Carbohydrates-III:Regulation of Blood Sugar,Insulin and Diabets Mellitus

Carbohydrates-III 71

Q. What is the best method for glucose estimation?(Page 91)

A. Glucose oxidase peroxidase (GOD-POD) method.

Q. What is the major indication for doing an oralglucose tolerance test (OGTT)? (Page 92)

A. Patient has symptoms suggestive of diabetes mel-litus, but fasting blood sugar value is inconclu-sive (between 100 and 126 mg/dl).

Q. What are the precautions to take before OGTT?(Page 92)

A. Patient should have a good carbohydrate diet forthree days prior to the test. Patient should avoidinsulin and oral antidiabetic drugs. Patient shouldfast overnight. Patient should not take any break-fast.

Q. What is the glucose load dose? (Page 92)A. Seventy five gram anhydrous glucose (82.5 g of

glucose monohydrate) in 250-300 ml of water.

Q. What precaution would you take in giving theglucose load? (Page 92)

A. In order to prevent vomiting, patient is asked todrink it slowly (within about 5 minutes).Flavouring of the solution will also reduce thetendency to vomit.

Q. What are the criteria for diagnosing diabeticmellitus? (Table 10.1). (Page 92)

A. Fasting plasma sugar is more than 126 mg/dl, onmore than one occasion. 2. Or, if 2-hour post-glu-cose load value of OGTT is more than 200 mg/dl(even at one occasion). 3. Or, if both fasting and 2-hour values are above these levels, on the sameoccasion.


Q. Can you diagnose diabetes on the basis of ran-dom blood estimations? (Page 92)

A. Diabetes is diagnosed, if the random plasma sugarlevel is more than 200 mg/dl, on more than oneoccasion. Diagnosis should not be based on asingle random test alone, it should be repeated.

Q. When a standard oral glucose tolerance test wasdone, the blood glucose levels of the patient werefound as:0 min = 130 mg/dl and 120 min = 220 mg/dl. What will be your diagnosis? (Page 92)

A. Diabetes mellitus.

Q. What is impaired glucose tolerance (IGT)?(Page 93)

A. When fasting plasma glucose level is between 110and 126 mg/dl and 2-hour post-glucose value isbetween 140 and 200 mg/dl.

Q. When a standard oral glucose tolerance test wasdone, the blood glucose levels of the patient werefound as:0 min = 120 mg/dl, 120 min = 160 mg /dl. What is your diagnosis?

A. Impaired glucose tolerance. (Page 93)

Q. What you will do for such persons? (Page 93)A. Such persons need careful follow up because IGT

progresses to frank diabetes at the rate of 2% pa-tients per year.

Q. What is impaired fasting glycemia (IFG).(Page 93)

A. In this condition, fasting plasma sugar is abnor-mal (between 110 and 126 mg/dl), but the 2-hourpost-glucose value is within normal limits (lessthan 140 mg/dl).


Q. What you will do for such persons? (Page 93)A. These persons need no immediate treatment, but

are to be kept under constant check-up. They areat increased risk for development of diabetes orcardiovascular diseases.

Q. What is gestational diabetes mellitus (GDM)?(Page 93)

A. This term is used when carbohydrate intoleranceis noticed, for the first time, during a pregnancy.If the fasting value is more than 126 mg%, it istaken as gestational diabetes.

Q. If a known diabetic patient, who becomes preg-nant, will you include her in the category ofGDM? (Page 93)

A. No.

Q. What is the clinical significance of GDM?(Page 93)

A. Women with GDM are at increased risk for sub-sequent development of frank diabetes. GDM isassociated with increased birth weight of childand increased incidence of neonatal mortality.

Q. After delivery, what you will do for a person withGDM? (Page 93)

A. After the child birth, the women should be re as-sessed and accordingly classified as having eitherdiabetes mellitus or normal glucose tolerance,based on the results of a fresh OGTT.

Q. What are other conditions which may cause im-paired glucose tolerance? (Page 93)

A. Alimentary glucosuria, renal glucosuria.


Q. What is renal glucosuria? (Page 93)A. Here glucose is excreted in urine due to a lower-

ing of renal threshold. The blood sugar levels arewithin normal limits.

Q. What is normal renal threshold for glucose?(Page 93)

A. 180 mg/100 ml.

Q. What are the reducing substances seen in urine?(Page 94)

A. Glucose, fructose, lactose, galactose, pentoses,ascorbic acid, glucuronides.

Q. What is transient glucosuria? (Page 94)A. It may occur in some people due to emotional

stress. Excessive secretion of catecholamines willproduce hyperglycemia and resultant glucosuria.Once theÿstress is removed, the glucosuria dis-appears.

Q. What is fructosuria? (Page 94)A. Presence of fructose in urine. It is due to the defi-

ciency of fructokinase or aldolase B (Fig.11.11).

Q. What is lactosuria? (Page 94)A. It is observed in the urine of normal women dur-

ing 3rd trimester of pregnancy and during lacta-tion.

Q. What is the clinical importance of lactosuria?(Page 94)

A. The condition is harmless. But it is important todistinguish lactosuria from glucosuria when ges-tational diabetes mellitus is suspected.


Q. What is the test for reducing sugars in urine?(Page 95)

A. Benedict�s test.

Q. What are the pathways stimulated by insulin?(Page 96)

A. Glycolysis, glycogen synthesis, HMP shunt path-way, lipogenesis.

Q. Name important enzymes that are stimulated byInsulin. (Page 96)

A. Phospho fructo kinase, glycogen synthase, glu-cose-6-phosphate dehydrogenase, acetyl CoA car-boxylase.

Q. What are the pathways inhibited by insulin?(Page 96)

A. Gluconeogenesis, glycogenolysis, lipolysis, keto-genesis.

Q. What are the important enzymes inhibited byinsulin? (Page 96)

A. Glucose-6-phosphatase, glycogen phosphorylase,hormone sensitive lipase.

Q. Where is insulin synthesised? (Page 96)A. Beta cells of langerhans of pancreas.

Q. What is proinsulin? (Page 96)A. Insulin is synthesised as a large single polypep-

tide. Middle part of it is then removed, to formthe A and B chains of insulin.

Q. What is C peptide? (Page 96)A. It is the part removed from proinsulin during the

maturation of insulin molecule.


Q. What is the clinical significance of C peptide?(Page 96)

A. Sometimes measurement of endogenous insulinmay be difficult because of the presence of anti-bodies against insulin in the circulation. Thenmeasurement of C-peptide is useful.

Q. What are the salient structural features of insu-lin? (Page 96)

A. Insulin is a protein hormone with two poly peptidechains, the A chain with 21 amino acids and the Bchain with 30 amino acids are joined together by apair of disulfide bonds. It has a total of 51 aminoacids.

Q. How is insulin secretion controlled? (Page 96)A. Glucose is the major stimulant of insulin secre-

tion.

Q. How glucose stimulates insulin secretion?(Page 96)

A. The beta cells have GluT 2 receptors, these act assensor mechanism for glucose level. The insulinsecretion is controlled by a cyclic AMP-mediatedmechanism. Cyclic AMP along with calciumcauses the insulin secretion.

Q. What is the effect of insulin on glucose uptakeof cells? (Page 97)

A. Insulin facilitates the membrane transport of glu-cose in most of tissues, especially in muscles andadipose tissue. This is by glucose transporter,GIuT4. But glucose uptake by GlT2 is indepen-dent of insulin, it is seen in liver and brain.


Q. Maximum glucose utilisation is seen in whichtissue? (Page 97)

A. At basal rates, brain utilises 60% of sugar oxidised.

Q. What is the mechanism of action of insulin?(Page 97)

A. Insulin acts by binding to membrane receptor, onthe target cells.

Q. What is the structural feature of insulin recep-tor? (Page 97)

A. Insulin receptor has four subunits, two alpha andtwo beta subunits. The alpha units are located onthe extracellular side, to which insulin binds. Thebeta subunits are towards cytoplasmic side. Betasubunit has tyrosine kinase activity.

Q. How diabetes mellitus is classified? (Page 99)A. Type 1 and type 2.

Q. What are the characteristic features of type 1, dia-betes mellitus?

A. Here circulating insulin level is deficient. Thesepatients are dependent on insulin injections. On-set is during adolescence. Rapid loss of bodyweight is observed. They are more prone to de-veloping ketosis.

Q. What about type 2 diabetes mellitus? (Page 100)A. Most of the patients belong to this type. Here cir-

culating insulin level is normal, but there is a rela-tive insulin deficiency. It is commonly seen in in-dividuals above 40 years. These patients are lessprone to developing ketosis.


Q. What is maturity onset diabetes of young(MODY)? (Page 100)

A. It is due to defective glucokinase.

Q. What are the cardinal symptoms of diabetes mel-litus? (Page 100)

A. Polyuria, polydypsia, polyphagia and weightloss.

Q. What is the reason for polyuria in diabetes mel-litus? (Page 100)

A. When the blood glucose level exceeds the renalthreshold glucose is excreted in urine. Due to os-motic effect, more water accompanies the glucose.

Q. What is the reason for polydypsia in diabetesmellitus? (Page 100)

A. To compensate for this loss of water, thirst centreis activated, and more water is taken (polydypsia).

Q. What is the reason for weight loss in diabetesmellitus? (Page 100)

A. The loss and ineffective utilisation of glucoseleads to breakdown of fat and protein.ÿThis wouldlead to loss of weight.

Q. What is the reason for polyphagia in diabetesmellitus? (Page 100)

A. To compensate the loss of glucose and protein,patient takes more food.

Q. What are the acute complications of diabetesmellitus? (Page 100)

A. Keto acidosis, hyperosmolar non-ketotic coma,lactic acidosis.


Q. What are the chronic complications of diabetesmellitus? (Page 101)

A. Thrombosis, paralysis, gangrene, micro-angiopa-thy, nephrosclerosis, cataract, peripheral neuropa-thy.

Q. What is micro-albuminuria? (Page 101)A. Albumin 50 to 300 mg/day in urine. It is a pre-

dictor of progressive renal damage, atheroscle-rotic diseases and cardiovascular mortality. Al-bumin more than 300 mg/day indicates overt dia-betic nephropathy.

Q. What is the cause for cataract in diabetes melli-tus? (Page 101)

A. Early development of cataract of lens is due tothe increased rate of sorbitol formation, causedby the hyperglycemia.

Q. What is the difference between glycosylationand glycation?

A. Enzymatic addition of any sugar to a protein iscalled �glycosylation� while non-enzymatic pro-cess is termed �glycation�. (Page 101)

Q. What is the basis of glycation? (Page 101)A. When there is hyperglycemia, proteins in the body

may undergo glycation. It is a non-enzymatic pro-cess. Glucose is added to the N-terminal aminogroup of proteins.


Q. What is the significance of glycated hemoglobin?(Page 101)

A. The determination of glycated hemoglobin is notfor diagnosis of diabetes mellitus, but for moni-toring the response of treatment. It is unaffectedby recent food intake or recent changes in bloodsugar levels. An elevated glycohemoglobin indi-cates poor control of diabetes mellitus. The riskof retinopathy and renal complications are pro-portionately increased with elevated glycatedhe-moglobin.

Carbohydrates-IV 81

Carbohydrates-IV:Other Metabolic Pathways(HMP Shunt Pathway,Fructose, Galactose,Glucuronic Acid, Alcohol)

Q. HMP shunt pathway use how much glucose?(Page 103)

A. About 10% of glucose molecules per day are en-tering in this pathway.

Q. What are the tissues in which HMP shunt path-way is significant? (Page 103)

A. Liver, adipose tissue, RBC, adrenal cortex, ovary,testis, mammary gland, lens.

Q. Which is the key enzyme of hexose monophos-phate shunt pathway? (Page 103)

A. Glucose-6-phosphate dehydrogenase.

Q. What is the hormonal control over HMP shuntpathway? (Page 103)

A. Insulin stimulates the pathway by activating thekey enzyme.


Q. Which enzyme generates NADPH? (Page 103)A. Glucose-6-phosphate dehydrogenase.

Q. What is the purpose of HMP shunt pathway?(Page 104)

A. It generates NADPH.

Q. What is the use of NADPH in biological systems?(Page 105)

A. For reductive biosynthesis.

Q. What reductive biosynthesis pathways needNADPH? (Page 105)

A. Fatty acid biosynthesis, synthesis of cholesterol,steroid hormones.

Q. Apart from reductive synthesis, NADPH is usedfor what purpose? (Page 105)

A. It is necessary to keep the integrity of RBC mem-brane, it is needed for keeping glutathione in re-duced state, it is required for keeping transpar-ency of lens, it is necessary for superoxide pro-duction inside macrophages.

Q. What about ATP generation? NADPH is used forthat? (Page 106)

A. No. NADPH is not used for ATP generation.

Q. Apart from NADPH generation, is there anyother purpose for the HMPshunt pathway?

(Page 106)A. The pathway is required for the synthesis of ri-

bose, the pentose phosphates are necessary fornucleotide (DNA and RNA) synthesis.

Carbohydrates-IV 83

Q. What is the manifestation of glucose-6-phosphatedehydrogenase deficiency? (Page 106)

A. Drug induced hemolysis and met-hemoglobinemia.

Q. Acute hemolytic episode after administration ofantimalarial drug is due to what? (Page 106)

A. Deficiency of glucose-6-phosphate dehydrogenase.

Q. What is the most common enzyme deficiency inman? (Page 106)

A. Glucose-6-phosphate dehydrogenase deficiency.

Q. What is the mode of hereditary transmission ofGPD deficiency? (Page 106)

A. It is transmitted as an x-linked recessive character.

Q. Is there any advantage of the abnormal gene?(Page 106)

A. The geographical distribution of GPD deficiencycorrelates well with the malarial endemicity. TheGPD deficiency offers resistance to malarial in-fection.

Q. What is the clinical significance of transketolaseenzyme? (Page 107)

A. The transketolase reaction is measured in RBCsas an index of the thiamine status of an individual.

Q. Abnormal transketolase leads to what clinicalcondition? (Page 107)

A. The occurrence of Wernick�s encephalopathy(seen in alcoholics and in thiamine deficiency) isdue to a genetic defect in the enzyme transketo-lase. It occurs owing to the enzyme having lowbinding capacity for TPP.


Q. Transketolase activity is decreased in the defi-ciency what? (Page 107)

A. Thiamine pyrophosphate (TPP).

Q. What is the purpose of uronic acid pathway?(Page 107)

A. It is used for conjugation of bilirubin, steroids,synthesis of gluco-saminoglycans.

Q. In lower animals, uronic acid pathway is usedfor what purpose? (Page 107)

A. For synthesis of ascorbic acid (vitamin C).

Q. What is essential pentosuria? (Page 107)A. Excretion of pentose (L-xylulose) in urine due to

the deficiency of xylitol dehydrogenase.

Q. What is its importance? (Page 107)A. It does not produce any harm. But it gives a posi-

tive reaction to Benedict�s test, so it should be dif-ferentiated from diabetes mellitus.

Q. What is the clinical significance of polyol path-way? (Page 107)

A. The elevated level of sorbitol has been implicatedin the development of neuropathy, cataract andretinopathy in diabetes mellitus.

Q. Fructokinase catalyses which reaction?(Page 108)

A. Fructose to fructose-1-phosphate.

Q. What is fructose intolerance? (Page 108)A. Due defective aldolase-B, fructose-1-phosphate

accumulates. This leads to accumulation of gly-cogen in liver, and hypoglycemia.

Carbohydrates-IV 85

Q. Free fructose is seen in which body fluid?(Page 108)

A. Seminal plasma.

Q. This fructose is produced by which pathway?(Page 107)

A. Polyol pathway of glucose.

Q. What is the clinical application of fructose esti-mation in semen? (Page 108)

A. Fructose is secreted by seminal vesicles. A blockin seminal vessels is indicated by the absence offructose in semen.

Q. What is fructosuria? (Page 108)A. It is a benign metabolic defect due to deficiency

of fructokinase. Urine gives positive Benedict�stest, and so it should be differentiated from dia-betes mellitus.

Q. Neonatal hypoglycemia is seen in which condi-tions? (Page 109)

A. Glycogen storage disease, type I, galactosemia,fructose intolerance.

Q. What are the features of galactosemia?(Page 109)

A. Congenital cataract, mental retardation, neonatalhypoglycemia, hepatosplenomegaly, positiveBenedict�s test.

Q. Congenital cataract is seen in which condition?(Page 109)

A. Galactosemia.


Q. Galactosemia is due the absence of which en-zyme? (Page 109)

A. Galactose-1-phosphate uridyl transferase.

Q. What is the treatment policy in galactosemia?(Page 110)

A. Lactose free diet is given for first five years of life.

Q. Why five years, why life-long treatment is notrequired? (Page 110)

A. By five years, the alternate pathway (galatose-1-phosphate pyrophosphorylase) becomes active.

Q. Why excessive intake of alcohol produces lacticacidosis? (Page 110)

A. During alcohol oxidation, NADH is generated,which converts pyruvate to lactate.

Q. Why excessive intake of alcohol produces hy-poglycemia? (Page 110)

A. Because ethanol inhibits gluconeogenesis.

Q. What are the results of chronic alcoholism?(Page 111)

A. Polyneuropathy, fatty liver, cirrhosis, Werneck�sencephalopathy.

Q. How N-acetyl neuraminic acid (sialic acid) issynthesised? (Page 111)

A. N-acetyl mannosamine-6-phosphate + phosphoenol pyruvate.

Carbohydrates-IV 87

Q. In glycoproteins, carbohydrate residues are at-tached to which group of the polypeptide chain?

(Page 112)A. Hydroxyl group of serine or threonine.

Q. Increased glucosaminoglycans in urine is seenin which condition? (Page 113)

A. Mucopolysaccharidosis.


Lipids-I:Chemistry, Digestion andAbsorption of Lipids

Q. How lipids are classified? (Page 115)A. Simple, compound and derived.

Q. Classify fatty acids. (Page 115)A. Depending on the total number of carbon atoms,

they are classified as even chain and odd chain.

Q. Which type is prevalent in human body?(Page 115)

A. Even chain fatty acids.

Q. Fatty acids are classified in any other manner?(Page 116)

A. They are also classified as saturated or unsatur-ated fatty acids.

Q. What fatty acids are generally present in humanfat? (Page 116)

A. Mainly Oleic acid, then comes palmitic acid andlinoleic acid.

Lipids-I 89

Q. How many carbon atoms are present in oleic acid?(Page 116)

A. 18 carbon, with one double bond.

Q. Name some unsaturated fatty acids. (Page 117)A. Oleic, linoleic, linolenic and arachidonic acids.

Q. Name some polyunsaturated fatty acids.(Page 117)

A. Linoleic, linolenic and arachidonic acids.

Q. What is the structure of linoleic acid?(Page 117)

A. 18 carbon, with two double bonds.

Q. What is the structure of linolenic acid?(Page 117)

A. 18 carbon with three double bonds.

Q. What is the structure of arachidonic acid?(Page 117)

A. 20 carbon with four double bonds.

Q. Which contains good quantity of PUFA?(Page 118)

A. Vegetable oils such as sunflower oil, ground nutoil.

Q. Which contains very low level of PUFA?(Page 118)

A. Coconut oil and animal fats.


Q. What is the advantage of storing energy as trig-lycerides in the body? (Page 119)

A. Space requirement is less, storage does not requirewater, can be mobilised whenever required, ca-pacity for storage is unlimited.

Q. What is saponification? (Page 119)A. Hydrolysis of fat by alkali is called are saponifi-

cation.

Q. Does saponification number of a fat moleculeincrease or decrease with the molecular weightof the fat? (Page 119)

A. Decreases with increase in molecular weight offat.

Q. Odour of rancid oil is due to what? (Page 119)A. Partial oxidation of fatty acids, with formation of

epoxides and peroxides of small molecularweight fatty acids.

Q. Complete digestion of triacyl glycerol (triglycer-ide) in gastro intestinal tract needs what en-zymes? (Page 120)

A. Pancreatic lipase, co-lipase, isomerase and bilesalts

Q. What is the function of pancreatic lipase?(Page 120)

A. Partial hydrolysis of triacyl glycerol. The prod-ucts are 2-mono acylglycerol (2-MAG) (?-mono-glyceride) and two fatty acid molecule (Fig. 12.7).

Lipids-I 91

Q. What is the function of isomerase? (Page 120)A. Isomerase shifts the ester bond from position 2 to

1, this is then hydrolysed by the lipase to formfree glycerol and fatty acid.

Q. Will there be complete breakdown of triglycer-ide into fatty acid in the gastro intestinal tract?

(Page 120)A. No, only partial digestion is possible.

Q. What are the final end products of digestion oftriglyceride? (Page 120)

A. 2-monoacyl glyceride (78%), 1-monoacyl glycer-ide (6%), glycerol and fatty acids (14%).

Q. How small chain fatty acids are absorbed?(Page 120)

A. Small chain and medium chain fatty acids (chainlength less than 14 carbons) are directly absorbedfrom the intestinal lumen into the portal vein andtaken to the liver.

Q. How long chain fatty acids are absorbed?(Page 120)

A. Long chain fatty acids (chain length more than 14carbons) are absorbed by forming micelles withthe help of bile salts.

Q. How bile salts help in the absorption of dietarylipids? (Page 120)

A. By emulsifying the lipids and producing micellesof lipids.

Q. What is the chemical name of bile salts?(Page 120)

A. Sodium glycocholate and sodium taurocholate.


Q. What are micelles? (Page 120)A. The micelles are spherical particles with a hydro-

philic exterior and hydrophobic interior core (Fig.12.8). Monoglycerides, long chain fatty acids, cho-lesterol, phospholipids and lysophospholipidsare incorporated into molecular aggregates toform mixed micelles.

Q. What happens to the micelles? (Page 120)A. Fatty acids and monoacyl glycerides from the mi-

celles passively diffuse into the mucosal cell.

Q. What happens to the fatty acids in the mucosalcell? (Page 120)

A. Once inside the intestinal mucosal cell, the longchain fatty acids are re-esterified to form triglyc-erides (Fig.12.9).

Q. What is the further fate of this triglyceride?(Page 121)

A. The triglyceride, along with phospholipids,apoproteins B48, and apo-A are incorporated intochylomicrons. The chyle (milky fluid) from theintestinal mucosal cells loaded with chylomicronsare transported through the lacteals into the tho-racic duct and then emptied into systemic circu-lation.

Q. What is the difference for absorption of shortchain fatty acid? (Page 120)

A. Short and medium chain fatty acids do not needre-esterification. They directly enter into bloodvessels (Not to lacteals).

Lipids-I 93

Q. Where will you find short and medium chainfatty acids? (Page 120)

A. They are seen in butter, ghee, coconut oil andmother�s milk.

Q. What happens to the bile salts of micelle?(Page 120)

A. The bile salts are left behind.

Q. What is enterohepatic circulation of bile salts?(Page 120)

A. They are separately reabsorbed from the ileumand returned to the liver to be re-excreted againto gut.

Q. What is steatorrhea? (Page 121)A. When excretion of fat in faeces is more than 6 g

per day, it is called steatorrhea.

Q. What is it due to? (Page 121)A. It is due to defective digestion as in chronic dis-

eases of pancreas. In such cases, unsplit fat is ex-creted in feces.

Q. What happens in defective absorption?(Page 121)

A. If the absorption alone is defective, most of thefat in faeces may be split fat, i.e. fatty acids andmonoglycerides.

Q. What is the cause for defective absorption of fat?(Page 121)

A. It may be due to diseases in intestinal mucosa,e.g. coeliac disease, sprue, Crohn�s disease.


Q. Any other cause for defective absorption of fat?(Page 121)

A. Any condition leading to a deficiency of bile saltscan also result in malabsorption of fat. The mostcommon causes are obstruction to biliary tract dueto gall stones, tumours of head of pancreas, en-larged lymph glands, etc.

Q. What is the line of management in defective ab-sorption? (Page 121)

A. In such cases, triglycerides with short chain andmedium chain fatty acids are digested and ab-sorbed properly, because they do not requiremicellerisation for absorption. Since milk fat andcoconut oil are made up of MCT, they are thera-peutically useful in malabsorption syndromes.

Lipids-II 95

Lipids-II:Metabolism of Fatty acids,Fatty acid oxidation,Fatty acid synthesis,Lipolysis, Ketone bodies.

Q. How fatty acids are activated in preparation ofoxidation? (Page 122)

A. Fatty acids are activated to their co-enzyme A(CoA) derivative.

Q. What is the enzyme for this activation?(Page 122)

A. Thiokinase or fatty acyl CoA synthetase.

Q. How much ATP is required for this reaction?(Page 122)

A. One molecule of ATP is hydrolysed to AMP andPPI. Thus two high energy bonds are utilised inthis reaction.

Q. What are the co-enzymes needed for fatty acidoxidation? (Page 122)

A. FAD and NAD.


Q. What is carnitine? (Page 122)A. Carnitine is beta-hydroxy-gamma-trimethyl am-

monium butyrate. It is synthesised from lysineand methionine in liver and kidney.

Q. What is the function of carnitine? (Page 122)A. Fatty acids are activated in the cytoplasm, but the

beta-oxidation is in mitochondria. The long chainfatty acyl CoA cannot pass through the inner mi-tochondrial membrane. Therefore a transporter,carnitine is involved in transfer of fatty acids.

Q. What about medium and small chain fatty ac-ids? (Page 122)

A. Medium chain fatty acids do not require carnitinefor transport, so they are easily oxidised.

Q. What is the net generation of ATP, when onemolecule of palmitic acid (16 carbon) is oxidisedcompletely? (Page 123)

A. 129.

Q. What are the products, during each cycle of betaoxidation of fatty acid? (Page 123)

A. Acetyl CoA, FADH2, and NADH.

Q. What are the energy producing steps in beta oxi-dation pathway? (Page 123)

A. Fatty acyl CoA dehydrogenase (FAD) and betahydroxy fatty acyl CoA dehydrogenase (NAD)steps.

Q. What is the product of beta oxidation of oddchain fatty acids? (Page 124)

A. Propionyl CoA.

Lipids-II 97

Q. What is the further metabolism of propionylCoA? (Page 124)

A. Propionyl CoA is first carboxylated to methylmalonyl CoA and then to form succinyl CoA. Thesuccinyl CoA then enters TCA cycle.

Q. What are the co-enzymes required for the con-version of propionyl CoA to succinyl CoA?

(Page 124)A. Biotin, ATP, Vitamin B12.

Q. Succinyl CoA is generated from which sub-stances? (Page 124)

A. Odd chain fatty acids, propionic acid, valine, iso-leucine, threonine.

Q. Succinyl CoA is utilised for what purposes?(Page 124)

A. Porphyrin biosynthesis, activation of acetoacetate,and oxidation in TCA cycle.

Q. What is alpha oxidation of fatty acid?(Page 124)A. It is a process by which fatty acids are oxidised

by removing carbon atoms, one at a time, fromthe carboxyl end. It is used for fatty acids that havea methyl group at the beta-carbon, which blocksbeta-oxidation. Alpha oxidation does not gener-ate energy.

Q. Where is alpha oxidation taking place?(Page 124)

A. In endoplasmic reticulum (microsomes).

Q. Refsum�s disease is due to what? (Page 125)A. Accumulation of phytanic acid, due to defective

alpha oxidation.


Q. What are the major differences between fatty acidsynthesis and beta oxidation of fatty acid?

(Page 125)A. Beta oxidation is taking place in mitochondria,

fatty acid synthesis is in cytoplasm. Oxidation en-zymes are independent, synthetic enzymes aregrouped as a multi-enzyme complex. During oxi-dation, 2 carbon units are removed as acetyl CoA,during synthesis, 2 carbon units are added as 3carbon malonyl CoA. For oxidation, NAD andFAD are necessary, for synthesis, NADPH is used.

Q. How NADPH is made available? (Page 128)A. In the HMP shunt pathway, glucose-6-phosphate

dehydrogenase reaction produces NADPH.

Q. What is the rate limiting enzyme of de novo syn-thesis of fatty acid? (Page 126)

A. Acetyl CoA carboxylase.

Q. What is the reaction? (Page 126)A. Acetyl CoA + CO2 ® Malonyl CoA.

Q. What are the co-enzymes required for the reac-tion? (Page 126)

A. Biotin and ATP.

Q. Acetyl CoA from mitochondria is transferred tocytoplasm for the de novo synthesis of fatty acid,by which enzyme? (Page 126)

A. ATP citrate lyase.

Q. What are the steps in which NADPH is used infatty acid synthesis? (Page 127)

A. Step 4 (Keto acyl reductase) and Step 6 (Enoyl re-ductase).

Lipids-II 99

Q. Acetyl CoA is used for what purposes?(Page 127)

A. Fatty acid synthesis, oxidation in citric acid cyclefor generation of energy, cholesterol synthesis andketone body formation.

Q. What are the sources of NADPH for fatty acidsynthesis? (Page 128)

A. Glucose-6-phosphate dehydrogenase, malic en-zyme, cytoplasmic malate dehydrogenase.

Q. How is fatty acid synthesis regulated?(Page 128)

A. Key enzyme, acetyl CoA carboxylase, is stimu-lated by citrate and inhibited by palmitoyl CoA.

Q. What is the action of insulin on fatty acid syn-thesis? (Page 128)

A. Insulin favours lipogenesis.

Q. How? (Page 128)A. Insulin enhances the uptake of glucose by

adipocytes and increases the activity of pyruvatedehydrogenase. So, availability of acetyl CoA isincreased. Insulin also activates glucose-6-phos-phate dehydrogenase, so that enough NADPH isavailable. Moreover, insulin stimulates acetylCoA carboxylase, the key enzyme of fatty acidsynthesis pathway. (Table 10.3). Insulin also de-presses the hormone sensitive lipase (Fig.13.11).

Q. Chain elongation of fatty acid is taking place inwhich site? (Page 128)

A. Microsomal elongation system is more active.


Q. Triacyl glycerol synthesis is enhanced by whichhormone? (Page 129)

A. Insulin.

Q. In adipose tissue, what is the source of glycerolphosphate for triglyceride formation?(Page 129)

A. From dihydroxy acetone phosphate, derived fromglucose.

Q. White adipose tissue is concerned with what?(Page 129)

A. Energy storage.

Q. Brown adipose tissue is involved in what pro-cess? (Page 129)

A. Thermogenesis.

Q. What enzyme is involved in lipolysis?(Page 129)

A. By hormone sensitive lipase.

Q. What is its action? (Page 129)A. In adipose tissue, hormone sensitive lipase hy-

drolyses triglyceride into fatty acid and releasesinto blood.

Q. In the blood, fatty acids are transported as whatform?

A. Albumin is the carrier of free fatty acid.

Q. Hormone sensitive lipase is activated by whichhormones? (Page 129)

A. Growth hormone, corticosteroids, ACTH,adrenalin, and glucagon.

Lipids-II 101

Q. Which are the lipolytic hormones? (Page 129)A. Growth hormone, corticosteroids, ACTH,

adrenalin, and glucagon.

Q. What is the mechanism of activation of hormonesensitive lipase? (Page 129)

A. A cascade through adenyl cyclase, cyclic AMP andkinase.

Q. What is the action of caffeine? (Page 129)A. It inhibits phospho diesterase, increases activity

of hormone sensitive lipase, and so, prolongs theaction of cyclic AMP. Thus, caffeine favours li-polysis.

Q. In diabetes mellitus, non-esterified fatty acidlevel in blood is increased, why? (Page 129)

A. Insulin inhibits hormone sensitive lipase, in dia-betes, this inhibition is removed, so, more lipoly-sis is taking place.

Q. What worsens fatty liver? (Page 130)A. Alcohol, diabetes mellitus, excess calorie intake,

hepatitis virus.

Q. What are the sources of acetyl CoA? (Page 130)A. Pyruvate, fatty acids, acetoacetyl CoA, and leu-

cine.

Q. What substances will prevent fatty liver?(Page 131)

A. Choline, methionine, lecithin.

Q. What are ketone bodies? (Page 131)A. Aceto acetate, beta hydroxy butyric acid, and ac-

etone.


Q. Ketone bodies are formed in which tissue?(Page 131)

A. Liver.

Q. Ketogenesis is taking place in which subcellularorganelle? (Page 131)

A. Mitochondria.

Q. What is the rate-limiting-step in ketone bodyformation? (Page 131)

A. HMGCoA synthase.

Q. HMGCoA is directly converted into what sub-stances? (Page 131)

A. Acetoacetate, acetyl CoA, mevalonate.

Q. Ketone body utilisation is taking place in whichorgans? (Page 131)

A. Ketolysis is taking place in extra hepatic tissues.(All other tissues, except liver).

Q. Utilisation of ketone bodies by peripheral tissuesneeds which enzyme? (Page 131)

A. Succinyl CoA dependent thiophorase.

Q. Ketosis is due to what processes? (Page 132)A. Step 1: Absence of insulin leads to excessive hy-

drolysis of triacyl glycerol. Step 2: So more fattyacid is available, and more acetyl CoA is pro-duced. Step 3: But oxidation of acetyl CoA in cit-ric acid cycle is sluggish. The excess acetyl CoAis diverted into ketone body formation.

Q. What test is used to identify ketone bodies inurine? (Page 132)

A. Rothera�s test.

Lipids-III 103

Lipids-III:Cholesterol, Lipoproteinsand Cardiovascular Diseases

Q. What is the ring structure present in cholesterol?(Page 133)

A. Perhydro cyclo pentano phenanthrene ring.

Q. Cholesterol has how many carbon atoms?(Page 133)

A. It has 27 carbon atoms.

Q. What are the substances derived from choles-terol? (Page 133)

A. Glucocorticoids, mineralocorticoids, testosterone,estrogen, bile acids.

Q. Which food stuffs contain cholesterol?(Page 133)

A. Non-vegetarian food.

Q. Whether cholesterol is present in vegetable oils?(Page 133)

A. No.


Q. What is the rate-limiting-step in the cholesterolbiosynthesis? (Page 134)

A. HMG CoA reductase.

Q. What is HMG CoA synthase? (Page 131)A. It is the rate-limiting-enzyme in ketogenesis path-

way.

Q. What is the first sterol ring formed during cho-lesterol biosynthesis? (Page 134)

A. Lanosterol.

Q. How cholesterol is excreted? (Page 135)A. Through bile, partly as cholesterol itself, and

partly as bile salts.

Q. What is the normal level of total plasma lipids?(Page 135)

A. 400-600 mg/dl.

Q. What is the normal level of total cholesterol?(Page 135)

A. 150-220 mg/dl.

Q. What is the normal level of triglycerides?(Page 135)

A. 50-200 mg/dl.

Q. How lipoproteins are estimated? (Page 136)A. Either by electrophoresis or by ultracentrifuga-

tion.

Q. During electrophoresis, what is the fastest mov-ing lipoprotein? (Page 136)

A. HDL (alpha lipoprotein).

Lipids-III 105

Q. During electrophoresis, what is the least mov-ing lipoprotein? (Page 136)

A. Chylomicron (gamma position).

Q. Maximum cholesterol content is in which lipo-protein? (Page 136)

A. LDL (Beta lipoprotein).

Q. Triglycerides present in chylomicrons are hy-drolysed by what? (Page 137)

A. Lipoprotein lipase.

Q. Where is the enzyme present? (Page 137)A. It is located at the endothelial layer of capillaries

of adipose tissue, muscles and heart, but not inliver.

Q. What is the main apoprotein present in chylo-micron. (Page 137)

A. B48.

Q. What is the function of chylomicron? (Page 137)A. Transport of triglycerides from intestine to adi-

pose tissue.

Q. Highest content of triglycerides is seen in whichlipoprotein? (Page 137)

A. Chylomicrons.

Q. Endogenous triglycerides in plasma are carriedby what? (Page 138)

A. VLDL.

Q. What is the main apoprotein present in LDL?(Page 138)

A. B100, it is the ligand for LDL receptor.


Q. What is the function of LDL receptors?(Page 138)

A. LDL receptors are present on all cells but mostabundant in hepatic cells and adrenal cortex. LDLreceptors, located in specialised regions calledclathrin-coated pits. When the apo B-100 binds tothe receptor, the receptor-LDL complex isinternalised by endocytosis.

Q. What is the function of LDL? (Page 138)A. Transport of cholesterol from liver to peripheral

tissues.

Q. What is �bad cholesterol�? (Page 139)A. LDL cholesterol.

Q. Why it is called so? (Page 139)A. LDL transports cholesterol from liver to periph-

eral tissues, where it is deposited, and causes ath-erosclerosis.

Q. What is lipoprotein(a) ? (Page 139)A. It is attached to apo B-100 by a disulfide bond. It

has significant homology with plasminogen. Soit interferes with plasminogen activation and im-pairs fibrinolysis (Fig.14.10). This leads to unop-posed intravascular thrombosis and possible myo-cardial infarction.

Q. What is the significance of lipoprotein (a)?(Page 139)

A. Lp(a) is associated with heart attacks at the age of30 or 40 years. Indians have a higher level of Lp(a)than Europeans.

Lipids-III 107

Q. What is the normal level of lipoprotein (a) ?(Page 139)

A. In 40% population, there is no detectable level ofLp(a) in serum. In 20% of population, the Lp(a)concentration in blood is more than 30 mg/dl, andthese persons are susceptible to heart attack at ayounger age.

Q. What is the function of HDL? (Page 139)A. Transport of cholesterol from peripheral tissues

to liver.

Q. What is �good cholesterol�? (Page 139)A. HDL cholesterol.

Q. Why it is called so? (Page 139)A. HDL transports cholesterol from peripheral tis-

sues to liver, and so helps in excretion of choles-terol from the body. So HDL is anti-atherogenic.

Q. What is the main apoprotein present in HDL?(Page 139)

A. Apo A-1, it is the ligand for HDL receptor.

Q. What is LCAT? (Page 139)A. Lecithin cholesterol acyl transferase.

Q. Where is it present? (Page 139)A. LCAT present in plasma is activated by apo-A1,

when LCAT binds to HDL disc.

Q. What is its importance? (Page 139)A. The free cholesterol is esterified by LCAT the es-

terified cholesterol is then incorporated into HDLdisc, to form mature HDL. So for excretion of cho-lesterol, LCAT is necessary.


Q. What is the importance of PUFA in cholesterolmetabolsim? (Page 140)

A. PUFA present in lecithin is transferred to choles-terol by the enzyme LCAT. The esterified choles-terol is then taken by HDL, and finally excretedthrough liver. So, for excretion of cholesterol,PUFA is required. Thus, PUFA will lower theblood level of cholesterol.

Q. Free fatty acids of plasma are bound to what?(Page 140)

A. Bound to serum albumin.

Q. What is the function of albumin? (Page 140)A. Transport of free fatty acid from adipose tissue to

peripheral tissues.

Q. Triglycerides present in adipose tissue are hy-drolysed by what enzyme? (Page 140)

A. Hormone sensitive lipase.

Q. What are the salient features of hyperlipoprotei-nemia Type II-A? (Page 141)

A. Premature atherosclerosis elevated plasma LDLcholesterol, and prominent beta band on electro-phoresis.

Q. What is it due to? (Page 141)A. Defect in LDL receptor.

Q. What is the treatment policy? (Page 141)A. Low cholesterol diet, decreased intake of satu-

rated fat, increased intake of PUFA, bile acid bind-ing resins.

Lipids-III 109

Q. What is the normal serum cholesterol level?(Page 142)

A. 150-220 mg/dl.

Q. Hypercholesterolemia is seen in what conditions?(Page 143)

A. Diabetes mellitus, nephrotic syndrome, obstruc-tive jaundice, hypothyroidism.

Q. How atherosclerosis started? (Page 143)A. The effect is directly proportional to the LDL lev-

els. Free radical induced oxidative damage ofLDL will accelerate this process. Oxidised LDL-cholesterol is deposited in the subintimal regionsof arteries.

Q. What tissues are affected mostly by atheroscle-rosis? (Page 143)

A. Aorta, coronary arteries and cerebral vessels arepredominantly affected.

Q. How LDL deposit leads to atherosclerosis?(Page 143)

A. Oxidised LDL is taken up by macrophages, themacrophages become overloaded with cholesterolesters, and these are then called �foam cells� whichform the hallmark of atherosclerotic plaques.

Q. What happens to atherosclerotic plaque?(Page 143)

A. This leads to narrowing of vessel wall. Then fibrousproliferation takes place, this is due to liberationof various growth factors. Again a clot is formedwhich occludes one of the major vessels. Then thereis ischemia of the tissue supplied. Finally infarc-tion or ischemic death of the tissue occurs.


Q. What are the important risk factors of coronaryartery diseases? (Page 144)

A. Serum cholesterol level above 220 mg/dl, LDL-cholesterol level above 160 mg/dl, HDL-choles-terol level below 35 mg/dl, and Apo(a) above 30mg/dl.

Q. What are other risk factors associated with coro-nary artery diseases? (Page 144)

A. Cigarette smoking, hypertension, diabetes melli-tus, serum triglyceride level above 200 mg/dl,homocysteine level, sedentary life style, obesity.

Q. What advise you will give to a person with in-creased cholesterol level? (Page 144)

A. Reduce food with higher cholesterol content offood, include PUFA and omega-3 fatty acids indiet, reduction of total fat intake of green leafyvegetables, exercise, avoid cigarettes.

Q. When will you start drugs for a person with in-creased cholesterol level? (Page 144)

A. When patient�s condition is not responding to thedietary restriction.

Q. What are the drugs available to treat hypercho-lesterolemia? (Page 144)

A. Bile acid binding recins, HMGCoA reductase in-hibitors, fibrate derivatives, nicotinic acid.

Q. What is the function of bile acids? (Page 146)A. They are the major route of excretion of choles-

terol and they are required for absorption oftriacyl glycerol.

Lipids-III 111

Q. Bile acids are derived from what substance?(Page 146)

A. Cholesterol.

Q. How are bile salts formed? (Page 146)A. Bile acids conjugated with taurine or glycine.


Lipids-IV:MCFA, PUFA andProstaglandins

Q. What is MCFA? (Page 147)A. Medium chain fatty acids they contain 8 to 14 car-

bon atoms.

Q. What is LCFA? (Page 147)A. Long chain fatty acids they contain 16 to 18 car-

bon atoms.

Q. What is VLCFA? (Page 147)A. Very long chain fatty acids they contain 20 or more

carbon atoms.

Q. What is the difference in digestion of MCT fromthat of LCFA?

A. MCT containing triglycerides are digested byMCT-specific lipase. Pancreatic lipase and bilesalts are not required. (Page 147)

Lipids-IV 113

Q. What is the difference in absorption of MCFAfrom that of LCFA?

A. MCFA is absorbed directly to blood (not tolacteals, as in the case of LCFA). Further, afterabsorption, MCFA is carried by albumin in blood,whereas LCFA are absorbed as triglycerides andcarried by chilomicrons. (Page 147)

Q. So what is the advantage of MCFA? (Page 147)A. MCFA are easily digested, easily absorbed, and

easily oxidised (when compared to LCFA).

Q. When palmitoleic acid (16 C, 1 double bond) iscompletely oxidised, what is the net generationof ATP molecules? (Page 147)

A. 127.

Q. When unsaturated fatty acids are oxidised, howmany ATP is formed?

A. The energy yield is less by 2 ATP molecules perdouble bond, when compared to the correspond-ing chain length saturated fatty acid. (Page 147)

Q. Why 2 ATP molecules are reduced? (Page 147)A. Because, the FAD dependent dehydrogenation

(step 1 of beta oxidation) does not occur at thedouble bond.

Q. Name polyunsaturated fatty acids. (Page 147)A. Linoleic, linolenic and arachidonic acids.

Q. What are essential fatty acids? (Page 148)A. Those cannot be synthesised by the body. So they

are to be provided in the diet.


Q. Name the essential fatty acids. (Page 148)A. Linoleic and linolenic acids are the only fatty ac-

ids which cannot be synthesised in the body.

Q. Where does desaturation of fatty acid takesplace? (Page 148)

A. In the endoplasmic reticulum.

Q. What is the enzyme called? (Page 148)A. Microsomal desaturase system.

Q. What are the important substances derived fromPUFA? (Page 148)

A. Prostaglandins, prostacycline, thromboxanes,leukotienes, HPETE.

Q. What are the functions of PUFA? (Page 148)A. Synthesis of prostaglandins, synthesis of phos-

pholipids and esterification of cholesterol.

Q. How prostaglandins are classified? (Page 149)A. According to the attachment of different substitu-

ent groups to the ring, PGs are named with capi-tal letters such as A, B, E and F. In the same series,depending on number of double bonds on theside chains they are denoted by a subscript afterthe capital letter, e.g. PGE1, PGE2, PGE3, etc. Se-ries 2 have two double bonds at 13-14 (trans) and5-6 (cis). This is the most common variety.

Q. Prostaglandins are derived from what substance?(Page 149)

A. Prostaglandins are derived from the PUFA. TheSeries 2 (with two double bonds) are derived fromarachidonic acid. All naturally occurring PGs be-long to the 2-series.

Lipids-IV 115

Q. Prostaglandins are stored in what form?(Page 149)

A. As precursors, as membrane phospholipids.

Q. How prostaglandins are synthesised?(Page 149)A. The arachidonic acid is released by the action of

phospholipase A2 on phospholipids prostaglan-din synthesis is catalysed by prostaglandin H syn-thase (PGHS). It contains two separate enzymeactivities, cyclo-oxygenase and peroxidase.

Q. How prostaglandin synthesis is regulated?(Page 150)

A. The phospholipase is activated by epinephrine.Steroids inhibit PL and prevent release of arachi-donic acid from membranes.

Q. What is the importance of cyclo-oxygenase?(Page 150)

A. Cyclo-oxygenase is activated by catecholaminesand inhibited by non-steroid anti-inflammatorydrugs (NSAIDS). Cyclo-oxygenase is a �suicide�enzyme.

Q. What is the mechanism of action of aspirin?(Page 150)

A. Aspirin acetylates serine in the active site and ir-reversibly inhibits the cyclo-oxygenase.

Q. How is prostaglandins inactivated? (Page 150)A. Prostaglandins have only very short half life, of

about 30 seconds. They are inactivated by the 15-hydroxy-prostaglandin-dehydrogenase whichconverts 15-OH group to keto group.


Q. What is the mechanism of action of prostaglan-dins? (Page 150)

A. Prostaglandins are local hormones, and functionthrough G-protein coupled receptors In most tis-sues, PGE increases cAMP level. But in adiposetissue and in renal tubular cells, PGE lowerscAMP level.

Q. What is the action of prostacyclin on vascular en-dothelium? (Page 150)

A. Prostacyclin causes vasodilatation. It also inhib-its platelet aggregation and has a protective ef-fect on vessel wall against deposition of platelets.

Q. What is the effect of thromboxane? (Page 150)A. Thromboxane (TXA2) is the main PG produced

by platelets. The major effects are vasoconstric-tion and platelet aggregation. Prostacyclin andthromboxane are opposing in activity.

Q. What is the precursor of leukotrienes?(Page 151)

A. They are produced from arachidonic acid.

Q. What is its biological importance? (Page 151)A. LT B4 is produced in neutrophils, it is the most

potent chemotactic agent. The slow reacting sub-stance of anaphylaxis (SRS-A) contains LTC4,LTD4 and LTE4. They cause smooth muscle con-traction, constrict the bronchioles, increase capil-lary permeability and produce vasoconstriction.

Lipids-IV 117

Q. What are VLCFAs? (Page 151)A. Fatty acids having 20 or more carbon atoms are

called very long chain fatty acids (VLCFA). Eicosapenta-enoic acid (EPA) (Timnodonic acid, C-20, 5double bonds) and docosa hexa-enoic acid (DHA)(cervonic acid, C-22, 6 double bonds) are goodexamples of VLCFA.

Q. What is the importance of DHA? (Page 151)A. DHA is synthesised linolenic acid. DHA can be

obtained from fish oils or from milk. DHA is es-pecially required for the development of brainand retina. Low levels of DHA in blood is seen inpatients with retinitis pigmentosa.


Lipids-V:Compound Lipids

Q. How phospholipids are classified? (Page 152)A. 1. Nitrogen containing glycero phosphatides, 2.

Non-nitrogen containing glycero phosphatides, 3.Plasmalogens, 4. Phospho sphingosides 5.Glycosphingolipids 6. Sulpholipids.

Q. What is Lecithin? (Page 152)A. Phosphatidyl choline.

Q. What is phosphatidic acid? (Page 152)A. Phosphatidic acid is made up of one glycerol to

which two fatty acid residues are esterified to car-bon atoms 1 and 2 and the 3rd hydroxyl group isesterified to a phosphoric acid.

Q. What is Cephalin? (Page 152)A. Phosphatidyl ethanol amine.

Lipids-V 119

Q. What is Cardiolipin? (Page 152)A. Diphosphatidyl glycerol.

Q. What is sphingomyelin? (Page 154)A. All sphingolipids have the long aliphatic

aminoalcohol sphingosine which is attached to afatty acid in amide linkage to form a ceramide. Acommon phosphosphingoside present abun-dantly in the nervous system, is sphingomyelin.It contains choline. Sphingomyelins are the onlysphingolipid that contain phosphate and have nosugar moiety.

Q. What is a cerebroside? (Page 154)A. Ceramide monohexoside.

Q. What is a globoside? (Page 154)A. Ceramide oligosaccharides.

Q. What is lung surfactant? (Page 153)A. It is produced by lung epithelial cells. Surfactant

decreases surface tension of the aqueous layer oflung and prevents collapse of lung alveoli.

Q. What are the constituents of surfactants?(Page 153)

A. Surfactants contain dipalmitoyl lecithin, phos-phatidyl glycerol, cholesterol and surfactant pro-teins A, B and C.

Q. What is its clinical significance? (Page 153)A. Low levels of surfactant leads to respiratory dis-

tress syndrome (RDS), which is a common causeof neonatal morbidity.


Q. Phospholipids can aggregate into what ?(Page 153)

A. Micelle and liposome.

Q. What is the nitrogenous base present in lecithin?(Page 153)

A. Choline.

Q. Cerebroside contains what? (Page 154)A. Sphingosine, fatty acid, hexose.

Q. On hydrolysis of sphingomyelin, what are ob-tained? (Page 154)

A. Sphingosine, fatty acid, phosphoric acid, choline.

Q. A ganglioside on hydrolysis, will give rise towhat? (Page 154)

A. Sphingosine, fatty acid, N-acetyl neuraminic acid.

Q. Name some lipid storage diseases. (Page 156)A. Tay Sach�s disease, Niemann Pick�s disease,

Gaucher�s disease.

Q. Gaucher�s disease is due to the deficiency ofwhat? (Page 157)

A. Beta glucosidase.

Q. What is accumulated in Gaucher�s disease?(Page 157)

A. Glucocerebroside.

Q. Niemann-Pick disease is due to the deficiencyof what? (Page 157)

A. Sphingomyelinase.

Lipids-V 121

Q. What is accumulated in Niemann-Pick disease?(Page 157)

A. Sphingomyelin.

Q. Tay Sach�s disease is due to the deficiency ofwhat? (Page 157)

A. Hexosaminidase.

Q. What is accumulated in Tay Sach�s disease?(Page 157)

A. Ganglioside.


Amino AcidMetabolism-I:General: Digestion,Absorption, Transamination,Urea

Q. What is the enzyme mainly responsible for pro-tein digestion in stomach? (Page 158)

A. Pepsin.

Q. What is the action of pepsin? (Page 158)A. It hydrolyses peptide bonds formed by carboxyl

groups of phenyl alanine, tyrosine, tryptophanand methionine.

Q. How pepsinogen is activated? (Page 158)A. Removal of N-terminal end by gastric hydrochlo-

ric acid.

Q. What are zymogens? (Page 158)A. They are pro-enzymes, inactive at the time of se-

cretion, but will be activated in the gastro intesti-nal tract.

Amino Acid Metabolism-I 123

Q. How the activation is effected generally?(Page 158)

A. Activation is achieved by removing a small partof the precursor molecules. Selective proteolysisproduces the catalytic site.

Q. What is its biological significance? (Page 158)A. Zymogens prevent autodigestion of the cells.

Q. What is its clinical significance? (Page 158)A. Acute pancreatitis results when trypsinogen is

activated prematurely.

Q. What are important enzymes in pancreatic juice?(Page 158)

A. Pancreatic juice contains the endopeptidasestrypsin, chymotrypsin and elastase.

Q. How trypsinogen is activated? (Page 159)A. The activation of trypsinogen is by removal of a

hexapeptide from N-terminal end by entero-ki-nase (enteropeptidase) present on the intestinalmicrovillus membranes.

Q. What is the action of trypsin? (Page 159)A. It hydrolyses peptide bonds formed by carboxyl

groups of arginine and lysine.

Q. How chymotrypsinogen is activated? (Page 159)A. It is activated by trypsin.

Q. What is an endopeptidase? (Page 159)A. It acts on peptide bonds inside the protein mol-

ecule, so that the protein becomes successivelysmaller and smaller units.


Q. Give some examples of an endopeptidase.(Page 159)

A. Trypsin, pepsin.

Q. What are exopeptidases? (Page 159)A. They act at one of the protein molecule, liberat-

ing amino acids sequentially, one at a time.

Q. Give an example exopepdases. (Page 159)A. Carboxypeptidase.

Q. What is carboxypeptidase? (Page 159)A. It is secreted by cells of intestinal villi, it is a

metallo-enzyme containing zinc, it is an endopep-tidase, spliting off carboxy terminal bond of theprotein.

Q. What is required for absorption of amino acids?(Page 160)

A. It needs the help of glutathione.

Q. What are cathepsins? (Page 160)A. Intracellular proteases.

Q. What is ubiquitin? (Page 160)A. It is necessary for intracellular protein breakdown.

Q. What are proteosomes? (Page 160)A. Ubiquitin tagged proteins are degraded inside the

cells, with the help of proteosomes.

Q. In fasting state, nitrogen is transported frommuscle as what form?

A. In the fasting state, the muscle releases mainlyalanine and glutamine of which alanine is takenup by liver and glutamine by kidneys.(Page 160)


Q. Transamination of glutamic acid produces what?(Page 161)

A. Alpha keto glutaric acid.

Q. What is the co-enzyme necessary for transami-nation reaction?

A. Pyridoxal phosphate. (Page 161)

Q. What are the physiological significance of tran-samination? (Page 161)

A. It synthesises non-essential amino acids, it helpsin the equalisation of quantities of amino acids, itis the first step of amino acid breaking down path-ways.

Q. What is the clinical significance of transamina-tion? (Page 161)

A. Transaminases are increased in blood in liver andcardiac diseases.

Q. What is transdeamination? (Page 161)A. Transamination takes place in all the cells of the

body, the amino group is transported to liver asglutamic acid which is finally oxidatively deami-nated in liver. Thus, the two components of thereaction are physically far away, but physiologi-cally they are coupled. Hence the term trans-deamination.

Q. Transamination reaction of pyruvate withglutamate results in the production of what sub-stances? (Page 161)

A. Alanine and alpha keto glutarate.


Q. Which amino acid is oxidatively deaminated inliver? (Page 162)

A. Glutamic acid.

Q. What is the reaction catalysed by glutamate de-hydrogenase?

A. Glutamate alpha keto glutarate + ammonia.(Page 162)

Q. What is the co-enzyme required for glutamatedehydrogenase?

A. NAD. (Page 162)

Q. Nitrogen atoms in the urea is derived from whatprecursors?

A. One from ammonia and another from aspartic acid.(Page 163)

Q. Ammonia is immediately trapped in brain bywhat? (Page 163)

A. Glutamine synthetase.

Q. What is the reaction catalysed by glutamine syn-thetase? (Page 163)

A. Glutamic acid + ammonia ® glutamine, this re-quires hydrolysis of ATP to ADP.

Q. What is the key enzyme of urea synthesis?(Page 163)

A. Carbamoyl phosphate synthetase.

Q. What are the two carbamoyl phosphate syn-thetases? (Page 164)

A. CPS-I is involved in urea synthesis, CPS-II is re-quired for pyrimidine synthesis. CPS-I is seen inmitochondria, while CPS-II is in cytosol.


Q. What is the normal blood urea level? (Page 165)A. 20-40 mg/dl.

Q. Blood urea level is markedly increased in whichcondition? (Page 165)

A. Renal diseases.

Q. What is the normal urinary excretion of urea?(Page 165)

A. 15-30 mg/day.


Amino AcidMetabolism-II:Simple, Hydroxy and SulfurContaining Amino AcidsGlycine, Serine, Alanine,Threonine, Methionine, Cysteine

Q. Glycine is used for synthesis of what com-pounds? (Page 166)

A. Serine, Creatine, Purines, Heme, Glutathione, Bilesalts.

Q. For creatine synthesis, which amino acids areused? (Page 167)

A. Glycine, arginine, methionine.

Q. Guanido acetic acid is formed in which tissue?(Page 167)

A. Kidney.

Q. Guanido acetic acid is formed from what aminoacids? (Page 167)

A. Arginine + glycine.

Amino Acid Metabolism-II 129

Q. Where is creatine is synthesised? (Page 167)A. In liver.

Q. What is the significance of creatinine?(Page 167)A. Excretion is increased in muscle dystrophy.

Q. How creatinine is produced in the body?(Page 167)

A. By spontaneous degradation of creatine phos-phate.

Q. What are the sources of oxalic acid in urine?(Page 168)

A. Ascorbic acid and glycine.

Q. What is the cause of hyper oxaluria? (Page 168)A. Protein targeting defect.

Q. What are the important substances producedfrom serine? (Page 168)

A. Glycine, pyruvate,cysteine,selenocysteine, cho-line, phosphatidyl serine.

Q. On decarboxylation, serine will produce what?(Page 169)

A. Ethanol amine.

Q. Choline is derived from what? (Page 169)A. Serine.

Q. What is the product of transamination of ala-nine? (Page 169)

A. Pyruvic acid.


Q. What is the significance of glucose-alanine cycle?(Page 169)

A. During starvation, alanine is released from muscle,and is taken up by liver. In liver alanine is tran-saminated to pyruvate, and pyruvate undergoesgluconeogenesis.

Q. What are important substrates for transmethyla-tion reactions? (Page 170)

A. Guanido acetic acid, serine, nor-epinephrine, N-acetyl serotonin.

Q. What is the methyl donor in transmethylationreaction? (Page 170)

A. S-adenosyl methionine.

Q. Which amino acid has two optically active (asym-metric) carbon atom? (Page 170)

A. Threonine.

Q. What are the functions of glutathione?(Page 171)

A. Reduction of met-hemoglobin to hemoglobin,keeping RBC membrane integrity, carrying aminoacids across membranes, and detoxification ofperoxidases.

Q. What is glutathione? (Page 171)A. Gamma glutamyl cysteinyl glycine.

Q. Urine of a patient with homocystinuria will bepositive for which test?

A. Cyanide nitroprusside test. (Page 173)

Amino Acid Metabolism-II 131

Q. What is the defective enzyme in homocystinuria?(Page 173)

A. Cystathionine synthase.

Q. What are the characteristic features of homo-cystinuria? (Page 173)

A. Mental retardation, subluxation of lens, andthrombosis.

Q. Homocystinuria is due to abnormal metabolismof which amino acid? (Page 173)

A. Methionine.

Q. What is the defective enzyme in Cystathionuria?(Page 173)

A. Cystathionase.


Amino AcidMetabolism-III:Acidic, Basic and BranchedChain Amino Acids, Glutamicacid, Glutamine, Aspartic acid,Asparagine, Lysine, Nitric Oxide,Valine, Leucine, Isoleucine

Q. What are the major functions of glutamic acid?(Page 175)

A. Transamination, transdeamination, ammoniatrapping in brain, and production of gammaamino butyric acid.

Q. Transamination reaction of pyruvate withglutamate results in the production of what sub-stances? (Page 175)

A. Alanine and alpha keto glutarate.

Q. Which amino acid is oxidatively deaminated inliver? (Page 175)

A. Glutamic acid.

Q. What is the reaction catalysed by glutamate de-hydrogenase?

A. Glutamate ® alpha keto glutarate + ammonia.(Page 175)

Amino Acid Metabolism-III 133

Q. What is the co-enzyme required for glutamatedehydrogenase?

A. NAD. (Page 175)

Q. Ammonia is immediately trapped in brain bywhat? (Page 175)

A. Glutamine synthetase.

Q. What is the reaction catalysed by glutamine syn-thetase? (Page 175)

A. Glutamic acid + ammonia ® glutamine, this re-quires hydrolysis of ATP to ADP.

Q. What is the reaction catalysed by glutaminase?(Page 176)

A. Glutamine ® glutamic acid + ammonia.

Q. Glutaminase enzyme is used for what purpose?(Page 175)

A. Excretion of ammonia in kidney tubules.

Q. Transamination of glutamic acid will give rise towhat?

A. Alpha keto glutarate.

Q. Decarboxylation of glutamic acid will give riseto what?

A. Gamma amino butyric acid.

Q. What is GABA?

A. It is an inhibitory neurotransmitter. Which is pro-duced by decarboxylation of glutamic acid.

Q. Which will give rise to an inhibitory neurotrans-mitter? (Page 175)

A. Glutamic acid.


Q. Glutamic acid can be formed from which aminoacids? (Page 175)

A. Histidine, arginine, proline, glutamine.

Q. Transamination of pyruvic acid will give rise towhat? (Page 175)

A. Alanine.

Q. Transamination of oxaloacetic acid will give riseto what? (Page 175)

A. Aspartic acid.

Q. What are the functions of glutamine? (Page 176)A. Ammonia trapping in brain (glutamic acid + am-

monia to glutamine), ammonia production in kid-ney (glutamine to glutamic acid + ammonia), syn-thesis of purine (Nitrogen 3 and 9), synthesis ofpyrimidine (3rd Nitrogen), synthesis of guanineand cytosine (amino groups).

Q. Alpha amino group of aspartic acid is incorpo-rated into which compounds? (Page 176)

A. Purines (1st nitrogen and 6th amino), pyrimidines(1st nitrogen and C4,5,6), and urea.

Q. Which amino acids are required for both purineand pyrimidine synthesis? (Page 176)

A. Aspartic acid, glutamine.

Q. What is asparaginase? (Page 176)A. Enzyme catalysing the reaction asparaginase to

aspartic acid + ammonia.

Q. What is its function? (Page 176)A. Ammonia production in kidney tubules.

Amino Acid Metabolism-III 135

Q. What is its clinical application? (Page 176)A. It is an anticancer drug against leukemias and

lymphomas. The leukemia cells cannot synthesisglutamine, and the available glutamine is de-stroyed by glutaminase, leukemia cells will starveand die.

Q. Lysine is deficient in which food stuffs?(Page 176)

A. Lysine is deficient in cereals.

Q. Carnitine is synthesised from which amino acid?(Page 177)

A. Lysine.

Q. Nitric oxide synthase system needs which co-enzymes? (Page 178)

A. FAD, FMN, tetra hydro biopterine, NADPH.

Q. What are the iso-enzymes of nitric oxide syn-thase? (Page 178)

A. Neuronal NOS, inducible NOS (macrophages) andendothelial NOS.

Q. What are the major functions of nitric oxide?(Page 178)

A. Vasodilatation, keeping the normal blood pres-sure, inhibitioin of adhesion of platelets, memoryprocess in brain, bactericidal in macrophages.

Q. What is the precursor of nitric oxide? (Page 178)A. Arginine.

Q. Which will give rise to polyamines? (Page 179)A. Ornithine.


Q. What are polyamines? (Page 179)A. Polyamines are putrescine, spermine and sper-

midine.

Q. What are the functions of polyamines?(Page 179)

A. They are growth factors, their concentration is in-creased in cancer.

Q. Name some mono amines. (Page 180)A. Histamine, dopamine, and serotonin.

Q. What about glutamine? Is it an amine?(Page 180)

A. No. Glutamine is an amide of glutamic acid.

Q. Valine enters in which metabolism? (Page 180)A. Valine is glucogenic.

Q. Leucine enters in which metabolism?(Page 180)A. Leucine is ketogenic.

Q. Isoleucine joins in which metabolism?(Page 180)

A. Isoleucine is partly glucogenic and partly keto-genic.

Q. Branched chain keto acids are excreted in urinein what condition?

A. Maple syrup urine disease. (Page 180)

Q. What is the defect in maple syrup urine disease?(Page 180)

A. Deficient decarboxylation of branched chain ketoacids.

Amino Acid Metabolism-IV 137

Amino AcidMetabolism-IV:Aromatic Amino Acids:Phenyl alanine, Tyrosine,Tryptophan, Histidine

Q. Which amino acids are both glucogenic andketogenic? (Page 181)

A. Phenyl alanine, tyrosine, tryptophan, andisoleucine.

Q. What are the important substances synthesisedfrom tyrosine?

A. Melanin, thyroxine, epinephrine and nor-epinephrine. (Page 182)

Q. What is the immediate precursor of norepine-phrine? (Page 182)

A. Dopamine.

Q. In pheochromocytoma, urine contains whatsubstance? (Page 183)

A. Vanillyl mandelic acid.


Q. Phenyl alanine level in blood is increased inwhat condition?

A. Phenyl ketonuria. (Page 183)

Q. What is the defective enzyme in phenyl ketonuria?(Page 183)

A. Phenyl alanine hydroxylase.

Q. What are the co-enzymes required for phenylalanine hydroxylase?

A. NADH, NADPH, tetrahydro bioptrin. (Page 181)

Q. Phenyl alanine, on transamination will give riseto what? (Page 183)

A. Phenyl pyruvate.

Q. What are the salient features of phenylketonuria?(Page 184)

A. Mental retardation, hyperactivity, high bloodphenyl alanine.

Q. Phenyl pyruvic acid is excreted in urine in whichcondition?

A. Phenyl ketonuria. (Page 184)

Q. Homogentisic acid is excreted in urine in whichcondition?

A. Alkaptonuria. (Page 184)

Q. What is the defective enzyme in alkaptonuria?(Page 184)

A. Homogentisic acid oxidase.

Q. Ochronosis is a manifestation of which condition?(Page 184)

A. Alkaptonuria.


Q. What is associated manifestation of albinism?(Page 184)

A. Nystagmus.

Q. A person�s urine was found to turn black onstanding and gave a positive Benedict�s test. Heis likely to have what condition? (Page 184)

A. Alkaptonuria.

Q. In phenyl ketonuria, urine will be positive forwhat test? (Page 184)

A. Ferric chloride test.

Q. What is the defect in tyrosinemia type I (hepato-renal tyrosinemia)?

A. Fumaryl acetoacetate hydrolase deficiency.(Page 185)

Q. What is the defect in tyrosinemia type II (oculocu-taneous tyrosinemia? (Page 185)

A. Deficiency of tyrosine amino transferase.

Q. Tryptophan is deficient in which food stuff?(Page 185)

A. Maize and corn.

Q. Xanthurenic acid in urine is seen in whichcondition? (Page 185)

A. Pyridoxal deficiency.

Q. What are the important substances producedfrom tryptophan?

A. Serotonin, melatonin, niacin, alanine, andacetoacetate. (Page 186)


Q. Which amino acid will give rise to a vitamin?(Page 186)

A. Tryptophan.

Q. Serotonin is derived from which amino acid?(Page 186)

A. Tryptophan.

Q. What are the characteristic features of malignantcarcinoid syndrome (argentaffinoma)?(Page 186)

A. Niacin deficiency, increased serotonin production,increased hydroxy indole acetic acid excretion,fluctuating hypertension.

Q. Pellagra is manifested in which conditions?(Page 186)

A. Niacin deficiency, pyridoxal deficiency, trypto-phan deficiency, and carcinoid syndrome.

Q. What is Hartnup�s disease? (Page 188)A. Absorption of aromatic amino acids from intestine

as well as reabsorption from renal tubules aredefective. So tryptophan deficiency, and pellagra-like symptoms are seen.

Q. Tryptophan is excreted in large quantities inwhich condition?

A. Hartnup�s disease. (Page 188)

Q. In Hartnup�s disease, which test will give apositive test? (Page 188)

A. Obermeyer test will be positive in urine.


Q. Indican in urine is tested by what method?(Page 188)

A. Obermeyer test.

Q. What is indican? (Page 187)A. Putrefaction product of tryptophan.

Q. What is the amino acid which has maximumbuffering capacity at physiological pH?

(Page 188)A. Histidine.

Q. What is the decarboxylation product of histidine?(Page 188)

A. Histamine.

Q. Which is the vasodialator produced fromhistidine? (Page 188)

A. Histamine.

Q. What is the clinical significance of histamine?(Page 188)

A. It is a powerful vasodilator and mediator ofanaphylaxis.

Q. What is Figlu excretion test? (Page 189)A. In folic acid deficiency, there is a block in histidine

metabolism, and figlu is excreted in largequantities in urine.

Q. What is figlu? (Page 189)A. Formimino glutamic acid, it is a product of

histidine metabolism.


Amino AcidMetabolism-V:Inter-relations ofamino acid metabolisms,One carbon metabolism,Amino acidurias

Q. Tetra hydro folic acid is used for what purpose?(Page 190)

A. It is the carrier of one carbon compounds.

Q. Name one carbon compounds? (Page 190)A. Formyl, formimino, methenyl, hydroxymethyl,

methylene, and methyl.

Q. Which are the donors to one carbon pool?(Page 191)

A. Serine, choline, glycine, tryptophan, histidine.

Q. One carbon units are used for synthesis of what?(Page 191)

A. C2 of purine, C8 of purine, serine, dTMP, choline,creatine, epinephrine.

Citric Acid Cycle 143

Q. Which is the purely ketogenic amino acid?(Page 192)

A. Leucine.

Q. What are partially ketogenic and partiallyglucogenic amino acids?

A. Phenyl alanine, tyrosine, tryptophan, isoleucine.(Page 192)

Q. What are important aminoacidurias which causemental retardation? (Page 192)

A. Phenyl ketonuria, homocystinuria, maple syrupurine disease.

Q. What is the defect in phenylketonuria?(Page 192)

A. Deficiency of phenyl alanine hydroxylase.

Q. What is the defect in alkaptonuria? (Page 192)A. Deficiency of homogentisic acid oxidase.

Q. What is the defect in homocystinuria (type 1)?(Page 192)

A. Deficiency of cystathionine beta synthase.

Q. What is the defect in maple syrup urine disease?(Page 193)

A. Deficiency of branched chain keto acid decar-boxylase.

Q. What is the defect in cystathionuria? (Page 193)A. Deficiency of cystathionase.

Amino Acid Metabolism-V 143


Q. What are the steps in which carbon dioxide isliberated, during the oxidation of glucose?

(Page 195)A. Pyruvate dehydrogenase, isocitrate dehydro-

genase, alpha keto glutarate dehydrogenase.

Q. Acetyl CoA is produced from what substrates?(Page 194)

A. Pyruvate, fatty acids, and leucine.


A. Oxidation in TCA cycle, fatty acid synthesis,cholesterol synthesis, and ketone body formation.

Q. Give examples of substrate level phosphoryla-tion. (Page 195)

A. 1,3-bisphospho glycerate kinase, pyruvate kinase,and succinate thiokinase.

Citric Acid Cycle

Citric Acid Cycle 145

Q. Which is the substrate level phosphorylation stepin the TCA cycle?

A. Succinate thiokinase. (Page 194)

Q. What is the inhibitor of succinate dehydroge-nase? (Page 197)

A. Malonate.

Q. Give examples of reactions in which NADH isgenerated. (Page 197)

A. Pyruvate dehydrogenase, isocitrate dehydro-genase, and alpha keto glutarate dehydrogenase.

Q. How many ATPs are generated per one rotationof the citric acid cycle? (Page 197)

A. 12 ATP.

Q. What is the net yield of ATP from one moleculeof glucose in anaerobic glycolysis? (Page 79)

A. 2 ATP.

Q. What is the net yield of ATP from one moleculeof glucose in aerobic glycolysis? (Page 79)

A. 8 ATP.

Q. During complete oxidation, what is the net yieldof ATP from one glucose molecule? (Page 79)

A. 38 ATP.

Q. Which is the amphibolic pathway? (Page 197)A. Citric acid cycle.

Q. How TCA cycle is regulated? (Page 198)A. Availability of ATP, NAD+ and oxaloacetate.


Q. Succinyl CoA is formed from which substrates?(Page 199)

A. Isoleucine, valine, methionine, andodd chain fattyacids.

Q. Fumarate is produced from which substances?(Page 199)

A. A. Arginino succinate B. Phenyl alanine.

Q. Alpha keto glutaric acid is formed from whichsubstances? (Page 199)

A. Glutamic acid, histidine, arginine, and proline.

Q. Aspartic acid enters the TCA cycle at which level?(Page 199)

A. Oxalo acetate.

Q. In normal resting state, most of the glucose isutilised by which tissue?

A. Brain. (Page 200)

Q. What is the approximate percentage of storageform of energy (total fuel reserve) present in anormal human body? (Page 200)

A. Fat 85%, glycogen 1%, protein 14%.

Q. During starvation, which substances areincreased in blood? (Page 201)

A. Ketone bodies, glucagon, and epinephrine.

Electron Transport Chain 147

ElectronTransport Chain

Q. Give examples of high energy compounds.(Page 206)

A. ATP, GTP, creatine phosphate, 1,3-bis phosphoglycerate, phosphoenol pyruvate, acetyl CoA, andsuccinyl CoA.

Q. On hydrolysis of 1 mole of ATP to ADP, the releaseof energy will be approximately how much?

(Page 206)A. 7 kCal.

Q. Where is respiratory chain located? (Page 207)A. In the inner mitochondrial membrane.

Q. How is respiratory chain organised? (Page 207)A. Components are organised into four complexes.

Q. What are the activities taking place insidemitochondria? (Page 207)

A. Citric acid cycle, electron transport chain, and betaoxidation fatty acid.


Q. Where are enzymes of citric acid cycle located?(Page 207)

A. Fluid matrix contains enzymes of citric acid cycle.

Q. What is the function of Co-enzyme Q?(Page 208)

A. It catalyses the electron transport from complex Ior II to complex III.

Q. Cytochrome oxidase is present in which complex?(Page 209)

A. Complex IV.

Q. What are NAD+ linked dehydrogenases?(Page 209)

A. Glyceraldehyde-3-phosphate dehydrogenase,pyruvate dehydrogenase, alpha keto glutaratedehydrogenase, isocitrate dehydrogenase, malatedehydrogenase, beta hydroxy acyl CoA dehydro-genase.

Q. What are FAD-linked dehydrogenases?(Page 209)

A. Succinate dehydrogenase, and acyl CoA dehydro-genase.

Q. Which cytochromes contain copper? (Page 209)A. Cytochrome oxidase.

Q. What is valinomycin? (Page 210)A. It acts as an ionophore, dissipates the proton

gradient, and so inhibits ATP synthesis.

Q. What is atractylocide? (Page 210)A. It inhibits translocase, and inhibits ATP synthesis.

Electron Transport Chain 149

Q. What are the salient features of ATP synthase?(Page 210)

A. It has two subunits, Fo is a proton channel, andF1 has catalytic activity.

Q. How many ATP are produced in the oxidationof one molecule of NADH? (Page 210)

A. Three.

Q. How many ATP are produced in the oxidationof one molecule of FADH? (Page 210)

A. Two.

Q. Which is complex V of respiratory chain?(Page 210)

A. ATP synthase.

Q. What is oligomycin? (Page 210)A. It inhibits oxidative phosphorylation.

Q. Name some inhibitors of oxidative phosphory-lation. (Page 211)

A. Oligomycin, carbon monoxide, and cyanide.

Q. Which inhibits electron transport chain at site 1?(Page 211)

A. Barbiturate.


A. Naphthoquinone.


A. Carbon monoxide and cyanide.


Q. What is the cause for death due to cyanidepoisoning? (Page 211)

A. Cyanide inhibits cytochrome oxidase.

Q. Which is a physiological uncoupler? (Page 211)A. Thyroxine.

Q. Which is the inborn error due to a mutation inNADH-Q reductase?

A. Leber�s hereditary neuropathy (LHON).(Page 211)

Plasma Proteins 151

Free Radicalsand Anti-oxidants

Q. Name the free radicals.

A. Superoxide anion radical, hydroperoxyl radical,hydrogen peroxide, hydroxyl radical, lipidperoxide radical, singlet oxygen, nitric oxide, andperoxy nitrite.

Q. What are the important characteristics of reactiveoxygen species?

A. Extreme reactivity, short life span, generation ofnew ROS by chain reaction, and damage tovarious tissues.

Q. What are the enzymes generating ROS inmacrophages?

A. NADPH oxidase, superoxide dismutase, andmyeloperoxidase.

Free Radical and Anti-oxidants 151


Q. What are the biological effects of ROS?

A. Protein damage, loss of function, lipid peroxi-dation, membrane damage, mitochondrialdamage, DNA damage, cell death, mutation, andcancer.

Q. What are the free radical scavinging enzymes?

A. Superoxide dismutase, glutathione peroxidase,glutathione reductase, and catalase.

Q. ROS causes what diseases?

A. Chronic inflammation, rheumatoid arthritis, acuteinflammations, bronchopulmonary dysplasia,respiratory distress syndrome, retrolentalfibroplasia, cataract, reperfusion injury, athero-sclerosis, and peptic ulcer.

Q. Name important anti-oxidants.

A. Alpha tocopherol (Vitamin E), Vitamin C, VitaminA, and beta carotene.

Plasma Proteins 153

Q. What is normal serum albumin level?(Page 216)A. 3.5-5 mg/dl.

Q. What is the normal value of total proteins inserum? (Page 216)

A. 6-8 g/100 ml.

Q. Edema due to hypoproteinemia is seen in whichconditions? (Page 217)

A. Cirrhosis liver, malnutrition, and nephroticsyndrome.

Q. In blood, albumin carries what substances?(Page 217)

A. Free fatty acids, bilirubin, salicylate, and calcium.

Q. What is the clinical application of albumincarrying bilirubin? (Page 217)

A. Bilirubin and salicylate compete for binding toalbumin, and so it is not safe to give salicylate toinfants having hemolytic disease.

Plasma Proteins


Q. What are the functions of albumin? (Page 217)A. It maintains colloidal osmotic pressure of plasma,

and it transports non-esterified fatty acid andbilirubin.

Q. Albumin is synthesised in which organ?(Page 217)

A. Liver.

Q. Where is gamma globulins synthesised?(Page 217)

A. By reticulo endothelial system (Spleen, lymphnodes).

Q. Polymorphism is exhibited by which proteins?(Page 218)

A. Haptoglobin, transferrin, and ceruloplasmin.

Q. Albumin globulin ratio is reversed in whichconditions? (Page 218)

A. Cirrhosis, chronic infections, nephrotic syndrome,and multiple myeloma.

Q. Name some transport proteins. (Page 218)A. Transthyretin (thyroid hormones), retinol binding

protein, thyroxine binding globulin, transcortin(cortisol), haptoglobin (hemoglobin), transferrin(Iron), and hemopexin (free heme).

Q. Name acute phase proteins. (Page 219)A. C-reactive protein, ceruloplasmin, and hapto-

globin.

Plasma Proteins 155

Q. What is the clinical manifestation of Alpha-1-anti-trypsin deficiency? (Page 219)

A. Emphysema and chronic lung infections.

Q. What is ceruloplasmin? (Page 219)A. It is a copper containing enzyme (ferroxidase)

seen in blood. It is an acute phase protein.

Q. What is the clinical significance of cerulo-plasmin? (Page 219)

A. Ceruloplasmin level in blood is decreased inWilson�s hepatolenticular degeneration.

Q. What is the carrier protein of copper? (Page 219)A. Albumin.

Q. Hemopexin carries what? (Page 220)A. Free heme.

Q. How hemophilia is manifested? (Page 222)A. Non-stopping hemorrhage after minor injuries.

Q. How hemophilia is transmitted? (Page 222)A. It is inherited as an x-linked recessive trait, males

are affected, females are carriers.

Q. Hemorrhage tendency is seen in which condi-tions? (Page 222)

A. Hemophilia, Vitamin K deficiency, and thrombo-cytopenia


Immunochemistry

Q. How immunoglobulins are classified?(Page 225)

A. IgG, IgM, IgA, IgD and IgE.

Q. What is the basic structure of an immunoglo-bulin? (Page 225)

A. Two heavy chains and two light chains connectedby disulphide linkages.

Q. The antigen binding capacity of immunoglobulinresides at which region of immunoglobulin?

(Page 225)A. Variable region.

Q. What is primary response antibody? (Page 226)A. Immunoglobulin M.

Q. What is the secondary response antibody?(Page 226)

A. Immunoglobulin G.

Heme Synthesis and Breakdown 157

Q. Which antibody is seen in body secretions?(Page 227)

A. Immunoglobulin A.

Q. What is the clinical importance of immunoglo-bulin E? (Page 227)

A. They mediate anaphylactic reaction.

Q. What is the cause of anaphylactic reaction?(Page 227)

A. IgE attach on mast cells, when antigen isintroduced, antigen antibody reaction occurs, andleading to mast cell degranulation.

Q. What is M band? (Page 228)A. A narrow peak in gamma globulin, caused by

monoclonal antibodies secreted by malignantplasma cells.

Q. What is Bence Jones protein? (Page 228)A. It is the light chains of immunoglobulins, excreted

in urine. It is seen in urine of 20% cases of multiplemyeloma.

Q. What is the test done to detect Bence Jonesprotein? (Page 228)

A. It is precipitated when heated between 45 and 60degrees.

Q. How antibody diversity is produced?(Page 230)A. By somatic recombination.

Immunochemistry 157


Q. What is the structural arrangement of collagen?(Page 233)

A. It has triple stranded quarter staggeredarrangement. One-third residues are glycine.About 1% residues are proline and hydroxyproline.

Q. What are the post-translational modificationstaking place in collagen?

A. Hydroxylation of proline and lysine residues, andhydrolysis of pro-collagen. (Page 233)

Q. Hydroxylation of proline and lysine needs what?(Page 233)

A. It depends on vitamin C.

Q. In ascorbic acid deficiency, what happens?(Page 233)

A. Poor hydroxylation, defective collagen andscurvy.

Specialised Proteins:Collagen, Myosin


Q. Cross links in collagen are formed by what?(Page 234)

A. It is formed between lysine and hydroxy lysineresidues. It is called desmosine.

Q. What is the enzyme for cross linkage formation?(Page 234)

A. Lysyl oxidase.

Q. What is its clinical application? (Page 234)A. Lysyl oxidase contains copper. So, in copper

deficiency lysine cross-link formation is deficient,leading to defective collagen.

Q. What are inherited disorders leading to defectivecollagen formation?

A. Osteogenesis imperfecta, Ehlers-Danlos synd-rome, dermatoparaxis, homocystinuria, andmarfan�s syndrome. (Page 234)

Q. What is myosin? (Page 236)A. It is a specialised protein seen in muscle.

Q. What is its biological function? (Page 236)A. It can bind actin to form actomyosin. It has ATPase

activity.

Q. What is the function of Troponin-C ? (Page 237)A. It binds calcium.

Q. What is the function of Troponin-I ? (Page 237)A. ATPase inhibitory element.

Q. What is the clinical significance of Troponin-T ?(Page 237)

A. Its serum level is increased in myocardialinfarction.

Specialised Proteins: Collagen Myosin 159


Q. What is the chemical structure of heme?(Page 240)

A. It is ferro protoporphyrin.

Q. What are the substituent groups of heme?(Page 240)

A. Methyl, vinyl, and propionyl groups.

Q. Heme is synthesised from what substances?(Page 241)

A. It is synthesised from glycine and succinyl CoA.

Q. What is the rate limiting enzyme of hemesynthesis? (Page 241)

A. ALA synthase.

Q. Which enzyme is inhibited by lead? (Page 241)A. ALA dehydratase and ferrochelatase.

Q. Methenyl bridge of protoporphyrin is derivedfrom what? (Page 241)

A. Alpha carbon of glycine.

Heme Synthesisand Breakdown


Q. How is heme synthesis regulated? (Page 242)A. ALA synthase is repressed by heme, and ALA

synthase is allosterically inhibited by hematin.

Q. What is the action of barbiturates on hemesynthesis? (Page 242)

A. Barbiturates will induce heme synthesis.

Q. What is the treatment for acute intermittentporphyria? (Page 243)

A. High carbohydrate diet, and stoppage of barbitu-rates.

Q. What is the defect in acute intermittent porphyria?(Page 243)

A. PBG-deaminase.

Q. How porphyrins are detected? (Page 243)A. They show fluorescence under ultra violet light.

Q. In acute intermittent porphyria, urine containswhat? (Page 243)

A. ALA and PBG.

Q. Lead poisoning results in elevated levels ofwhat? (Page 244)

A. Delta amino levulinic acid.

Q. Degradation of heme needs which enzyme?(Page 245)

A. Heme oxygenase system, with NADPH.

Q. Degradation of heme to bilirubin releases whatgas? (Page 245)

A. Carbon monoxide.


Q. Heme is converted to bilirubin in which site?(Page 245)

A. Microsomes of reticulo-endothelial cells.

Q. Bilirubin in blood is carried by what?(Page 245)A. Albumin.

Q. How it is made water soluble? (Page 245)A. By conjugation with glucuronic acid.

Q. Where is the conjugation taking place?(Page 245)

A. In liver.

Q. What is the enzyme? (Page 245)A. UDP-glucuronyl transferase.

Q. What is the normal level of plasma bilirubin?(Page 246)

A. 0.2-0.8 mg/dl.

Q. What is the normal level of conjugated bilirubinin plasma? (Page 246)

A. Less than 0.2 mg /dl.

Q. What is latent jaundice? (Page 246)A. When plasma bilirubin is between 1 to 2 mg/dl.

Q. What is jaundice? (Page 246)A. When plasma bilirubin is more than 2 mg/dl, it

diffuses into tissues, causing yellowish discolou-ration of tissues.

Q. Enterohepatic circulation is seen in whichsubstances? (Page 246)

A. Urobilinogen and bile salts.


Q. What is the defect in Gilbert�s disease?(Page 247)

A. Uptake of bilirubin by the liver is defective.

Q. What is the defect in Criggler-Najjar syndrome?(Page 247)

A. Defect in conjugation of bilirubin due todeficiency of UDP glucuronyl transferase.

Q. Conjugated hyperbilirubinemia is seen in whichcondition? (Page 247)

A. Dubin Johnson�s syndrome.

Q. Bilirubin in serum is estimated by what test?(Page 247)

A. Van den Bergh reaction.

Q. What is Direct van den Bergh�s reaction?(Page 247)

A. The colour is developed immediately when bloodis added.

Q. What is your inference, when direct test ispositive? (Page 247)

A. Blood contains conjugated bilirubin, it is watersoluble.

Q. What is indirect van den Bergh�s test?(Page 247)A. When blood is added to the solution, there is no

colour, but when alcohol is added, colour isdeveloped.

Q. What is the reason for this type of reaction?(Page 247)

A. Bilirubin is soluble in alcohol, and alcohol extractgives the reaction.


Q. What is kernicterus? (Page 248)A. In young children, when plasma bilirubin is more

than 20 mg/dl, it diffuses into brain, causingpermanent damage to brain cells.

Q. In obstructive jaundice, what is seen in blood?(Page 248)

A. Conjugated bilirubin in excess quantity.

Q. Bile salts and bile pigments are excreted in urinein which condition?

A. Obstructive jaundice. (Page 248)

Q. Increased urobilinogen in urine is seen in whichconditions? (Page 248)

A. Congenital spherocytosis, mismatched transfu-sion, Rh incompatibility, auto-immune hemolysis,and glucose-6-phosphate dehydrogenasedeficiency.

Haemoglobins 165

Haemoglobins

Q. What are the salient structural features ofhemoglobin molecule?

A. Hb has four subunits, two alpha and two betaunits. It contains four iron atoms.

Q. How many molecules of oxygen can bind withhemoglobin?

A. Hb can bind four molecules of oxygen.(Page 249)

Q. 100 ml of blood can carry how much oxygen?(Page 250)

A. 20 ml.

Q. What is Bohr effect? (Page 251)A. The influence of pH and pCO2 to facilitate

oxygenation of Hb in the lungs and deoxyge-nation at the tissues is known as the Bohr effect.

Q. What is chloride shift? (Page 251)A. When CO2 is taken up, chloride ions from the

plasma would enter. This is called chloride shiftor Hamburger effect.


Q. Hemoglobin carries how much CO2? (Page 251)A. Seventy five percent as isohydric transport and

15% as carbamino hemoglobin.

Q. What are the forms in which carbon dioxide istransported? (Page 251)

A. Dissolved form, isohydric transport, andcarbamino hemoglobin.

Q. What is isohydric transport of carbon dioxide?(Page 251)

A. There is minimum change in pH during thetransport.

Q. How this is effected? (Page 251)A. The H+ ions are buffered by the deoxy-Hb.

Q. Which will decrease the affinity of hemoglobinfor oxygen?

A. 2,3-BPG level. (Page 252)

Q. What is the structural difference between HbAand HbF?

A. HbA has two alpha and two beta chains, but HbFhas two alpha and two gamma chains.(Page 252)

Q. What are the laboratory tests to identify HbF?(Page 252)

A. HbF moves slower than HbA on electrophoresis,HbF is alkali resistant.

Q. What is the physiological significance of HbF?(Page 252)

A. Oxygen affinity is more for HbF than HbA. HbFis seen in foetal circulation.

Haemoglobins 167

Q. What is the clinical significance of HbF?(Page 252)

A. It is seen in adults in hemoglobinopathies andthalassemias.

Q. Why carbon monoxide becomes a poison?(Page 253)

A. Hb has more affinity to carbon monoxide thanoxygen.

Q. What is the treatment for carbon monoxidepoison? (Page 253)

A. Hyperbaric oxygen.

Q. Met-hemoglobin is found in which conditions?(Page 253)

A. Ingestion of nitrites, presence of HbM, GPDdeficiency.

Q. What is met-hemoglobin? (Page 253)A. Hemoglobin in which iron is in ferric state.

Q. What is the defect of met-hemoglobin?(Page 253)

A. It cannot release oxygen in tissues.

Q. What is the reagent used for colourimetricestimation of hemoglobin? (Page 254)

A. Drabkin�s reagent, to convert Hb to cyanmet-hemoglobin.

Q. What is hemoglobin S? (Page 254)A. The glutamic acid in the 6th position of beta chain

of HbA is changed to valine in HbS.


Q. What is the cause for sickle cell anemia?

A. Solubility of deoxy HbS is lower than deoxy HbA,so HbS is precipitated intracellularly, leading tosickle shape of RBC.

Q. How HbS is identified?

A. HbS is slower moving on electrophoresis thanHbA.

Q. What is sickle cell trait?

A. Heterozygous (AS) condition, one allele isnormal, the other is abnormal, so half of Hbmolecules are normal, and half abnormal.


A. Sickle cell trait persons will not have any diseasemanifestations, usually. But, at higher altitudes,hypoxia may cause manifestation of the disease.Chronic lung disorders may also producehypoxia-induced sickling in HbS trait.

Vitamin-I 169

Vitamin-I:Fat SolubleVitamins: A, D, E and K

Q. What is the pro-Vitamin for Vitamin A?(Page 259)

A. Beta carotene present in plants.

Q. What is the major function of Vitamin A?(Page 260)

A. In vision, as the Wald�s visual cycle.

Q. What causes the nerve impulse in retina?(Page 260)

A. Photo-isomerisation of 11-cis retinal to all trans-retinal.

Q. How is all trans-retinal regenerated? (Page 261)A. Trans-retinal is taken to liver, where it is made to

trans-retinol, then isomerised to cis-retinol andthen to cis retinal.

Q. What are the enzymes required for this regenera-tion? (Page 261)

A. Alcohol dehydrogenase and retinol isomerase.


Q. What are other minor biological roles of VitaminA? (Page 262)

A. Normal maintenance of epithelium and skin,glycoprotein synthesis, reproduction, celldifferentiation, and anti-oxidant role.

Q. What are the sources of Vitamin A? (Page 262)A. Carrot, mangoes, papaya, green leafy vegetables,

and fish liver oil.

Q. What are the deficiency manifestations ofVitamin A? (Page 262)

A. Night blindness, xerophthalmia, keratomalacia,and keratinisation of epithelium.

Q. Nyctalopia is due to the deficiency of whichVitamin? (Page 262)

A. Vitamin A.

Q. What is the daily requirement of Vitamin A?(Page 263)

A. 750 to 1000 microgram.

Q. How cholecalciferol is synthesised? (Page 263)A. From 7-dehydro cholesterol in the malpighian layer

of epidermis, by the action of ultra violet rays.

Q. How Vitamin D is activated? (Page 264)A. Cholecalciferol from skin reaches liver. There it

is hydroxylated to form 25-hydroxy cholecalciferol(25-HCC). It then reaches kidney, where furtherhydroxylation takes place to form 1,25-dihydroxycholecalciferol (DHCC).

Vitamin-I 171

Q. What is calcitriol? (Page 264)A. 1,25-dihydroxy cholecalciferol, or active Vitamin

D, contains three hydroxyl groups at 1, 3 and 25positions. So it is called calcitriol.

Q. Which Vitamin acts as a pro-hormone?(Page 264)

A. Vitamin D.

Q. What is the function of Vitamin D? (Page 264)A. It increases absorption of calcium from intestine,

and it also increases mineralisation of bone.

Q. How Vitamin D increases absorption of calcium?(Page 264)

A. Calcitriol binds to a cytoplasmic receptor. Thehormone-receptor complex interacts with DNAand causes transcription of specific genes thatcode for calbindin. Due to the increasedavailability of calcium binding protein, theabsorption of calcium is increased.

Q. How is Vitamin D deficiency manifested?(Page 265)

A. Rickets in children and osteomalacia in adults.

Q. In renal disease, oral doses of Vitamin D maynot be effective, why? (Page 265)

A. Hydroxylation and activation of Vitamin is takingplace in kidney.

Q. What are the causes of rickets? (Page 265)A. Chronic renal failure, liver diseases, and under-

exposure to sunlight.


Q. What is the daily requirement of Vitamin D?(Page 265)

A. 5-10 microgram.

Q. What is the chemical nature of Vitamin E?(Page 265)

A. Alpha tocopherol.

Q. What is the function of Vitamin E ? (Page 266)A. Anti-oxidant.

Q. What is the relationship of selenium with Vita-min E? (Page 266)

A. They act synergistically as anti-oxidants.

Q. What is the source of Vitamin E? (Page 266)A. Vegetable oils are rich sources of Vitamin E, e.g.

wheat germ oil, sunflower oil, safflower oil, cottonseed oil, and palm oil.

Q. What is the normal daily requirement of VitaminE? (Page 266)

A. 15 mg or 33 international units.

Q. What is the chemical nature of Vitamin K?(Page 266)

A. Naphthoquinone derivative.

Q. What is menadione? (Page 266)A. It is synthetic water soluble Vitamin K, widely

used in clinical practice.

Q. What is the function of Vitamin K? (Page 267)A. Gamma carboxylation of clotting factors such as

prothrombin.

Vitamin-I 173

Q. Deficiency of Vitamin K can occur in whichconditions? (Page 267)

A. Obstructive jaundice, antibiotic therapy, andadministration of dicoumarol.

Q. What is the mechanism of action of dicoumarol?(Page 267)

A. It competitively inhibits Vitamin K epoxidereductase.

Q. So, dicoumarol is used for what purpose?(Page 267)

A. To prevent intravascular thrombosis.

Q. Excess dicoumarol will produce what?(Page 267)A. Bleeding tendency.

Q. Which substance will inhibit Vitamin K?(Page 267)

A. Dicoumarol.

Q. Excess dose of Vitamin K in neonates may leadto which condition?

A. Hemolysis and jaundice. (Page 267)

Q. Bleeding tendency is common in the deficiencyof which? (Page 267)

A. Vitamin K, Vitamin C, and platelets.


Vitamin-II:Water soluble vitamins

Q. What is the source of thiamine? (Page 268)A. Aleurone layer of cereals (food grains) is a rich

source of thiamine. Whole wheat flour andunpolished rice and yeast are very good sources.

Q. Thiamine pyrophosphate is required for whichreactions ? (Page 268)

A. Transketolase, pyruvate dehydrogenase, andalpha keto glutarate dehydrogenase.

Q. Which Vitamin is required for oxidativedecarboxylation? (Page 268)

A. Thiamine pyrophosphate.

Q. In thiamine deficiency, what alterations are seenin blood ? (Page 269)

A. Increased pyruvic acid level and increasedtransketolase activity.

Vitamin-II 175

Q. What are the clinical manifestations of thiaminedeficiency? (Page 269)

A. Beriberi, Wernick�s syndrome, and polyneuritis.

Q. Beberi is due to the deficiency of which Vitamin?(Page 269)

A. Thiamine.

Q. What is the daily requirement of Vitamin B1(thiamine) ? (Page 269)

A. 1 to 1.5 milligram.

Q. Chronic alcoholism may lead to the deficiencyof which Vitamin?

A. Vitamin B1. (Page 269)

Q. Wernicke�s encephalopathy is due to thedeficiency of which Vitamin?


Q. What is the co-enzyme function of riboflavin ?(Page 269)

A. FMN and FAD dependent enzymes.

Q. What are the FAD dependent enzymes?(Page 270)

A. Succinate dehydrogenase, acyl CoA dehydro-genase, xanthine oxidase, glutathione reductase,glycine cleavage system, pyruvate dehydro-genase, and alpha ketoglutarate dehydrogenase.

Q. What are the manifestations of riboflavindeficiency? (Page 270)

A. Glossitis, cheilosis, angular stomatits, andcircumcorneal vascularisation.


Q. What is the dietary sources of riboflavin?(Page 270)

A. Rich sources are liver, dried yeast, egg, and milk.

Q. What is the daily requirement of riboflavin?(Page 270)

A. 1.5 mg per day.

Q. Which Vitamin is synthesised in the body?(Page 271)

A. Niacin.

Q. What is the co-enzyme function of niacin?(Page 271)

A. NAD and NADP.

Q. Name some important NAD dependent enzymes.(Page 271)

A. Lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, pyruvate dehydro-genase, beta hydroxy acyl CoA dehydrogenase,and mitochondrial isocitrate dehydrogenase.

Q. Name the NADPH generating reactions.(Page 271)

A. Glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malic enzyme, andcytoplasmic isocitrate dehydrogenase.

Q. What are the important NADPH utilisingreactions? (Page 271)

A. Beta keto acyl ACP dehydrogenase, alpha, betaunsaturated ACP dehydrogenase, HMGCoAreductase, met-hemoglobin reductase, dihydrofo-late reductase, and phenylalanine hydroxylase.

Vitamin-II 177

Q. Pellagra is seen in the deficiency of whichVitamin? (Page 271)

A. Niacin.

Q. What are the features of pellagra ? (Page 271)A. Dermatitis, diarrhea, and dementia.

Q. What is the precursor of niacin? (Page 271)A. Tryptophan.

Q. Tryptophan will give rise to how much niacin?(Page 272)

A. About 60 mg of tryptophan will yield 1 mg of niacin.

Q. Tryptophan is deficient in which food stuff?(Page 272)

A. Maize and corn.

Q. Which conditions will lead to symptoms ofpellagra? (Page 272)

A. Isoniazid therapy, low tryptophan content in diet,niacin deficiency, hartnup disease, and carcinoidsyndrome.

Q. What is the dietary sources of niacin?(Page 272)A. Natural sources of niacin are dried yeast, rice poli-

shing, liver, peanut, whole cereals, legumes, meatand fish. About half of the requirement is met bythe conversion of tryptophan to niacin. About 60mg of tryptophan will yield 1 mg of niacin.

Q. What is the daily requirement of niacin?(Page 272)

A. The R.D.A is 20 mg/day.


Q. Transamination reaction requires whichVitamin? (Page 272)

A. Pyridoxal phosphate.

Q. Pyridoxal phosphate is required for whatreactions? (Page 272)

A. Transamination reactions, decarboxylation of aminoacids, ALA synthase, glycogen phosphorylase.

Q. Give an example of transamination reaction.(Page 272)

A. Alanine transaminase (ALT) will catalyse thereaction, alanine to pyruvate.


A. Blood level of ALT is increased in liver diseases,AST is increased in myocardial infarction.

Q. Give some examples of decarboxylation reactions.(Page 273)

A. Glutamate to GABA (gamma aminobutyric acid),histidine to histamine, 5-hydroxy tryptophan toserotonin, cysteine to taurine, and serine toethanol amine.

Q. Xanthurenic acid in urine is seen in the deficiencyof which Vitamin?

A. Pyridoxal deficiency. (Page 273)

Q. What are the manifestations of pyridoxaldeficiency? (Page 273)

A. Infantile convulsions, peripheral neuritis,pellagra, and anemia.

Vitamin-II 179

Q. What is the reason for infantile convulsions inpyridoxal deficiency?

A. Pyridoxal phosphate is required for the forma-tion of GABA, and it is an inhibitory neurotrans-mitter, absence of which leads to hyper-excitationand convulsions. (Page 273)

Q. What is the reason for peripheral neuritis inpyridoxal deficiency?

A. PLP is involved in the synthesis of sphingolipids,so B6 deficiency leads to demyelination of nervesand consequent peripheral neuritis. (Page 273)

Q. What is the reason for pellagra-like disease inpyridoxal deficiency?

A. Since niacin is produced from tryptophan, one ofthe enzymes of this pathway is PLP dependent.So B6 deficiency in turn leads to niacin deficiencywhich is manifested as pellagra. (Page 273)

Q. Can you give an exmple of one Vitamin defi-ciency leading to another Vitamin deficiency?

(Page 273)A. PLP deficiency in turn leads to niacin deficiency

which is manifested as pellagra.

Q. What is the reason for anemia in pyridoxaldeficiency? (Page 273)

A. PLP is required for ALA synthase. In adultshypochromic microcytic anemia may occur dueto the inhibition of heme biosynthesis.


Q. What are the drugs which cause pyridoxaldeficiency? (Page 274)

A. Isonicotinic acid hydrazide (INH) (isoniazid),cycloserine, penicillamine and oral contracep-tives act as B6 antagonists. Ethanol in the body isconverted to acetaldehyde, which inactivates PLP.

Q. What are the dietary sources of pyridoxal?(Page 274)

A. Rich sources are yeast, rice polishing, wheatgerms, cereals, legumes (pulses), egg, milk, meat,fish and green leafy vegetables.

Q. What is the daily requirement of pyridoxalphosphate? (Page 274)

A. 1 to 2 mg/day.

Q. What is the co-enzyme form of pantothenic acid?(Page 274)

A. Co-enzyme A.

Q. What is the function of CoA? (Page 274)A. Oxidation of pyruvic acid and activation of acyl

groups.

Q. Deficiency of pantothenic acid leads to what?(Page 274)

A. Burning foot syndrome.

Q. What are the donors for acetyl CoA pool?(Page 275)

A. Pyruvate, fatty acid, and amino acids.

Vitamin-II 181


A. Oxidation in TCA cycle, fatty acid synthesis,cholesterol synthesis, steroid synthesis, andketone body formation.

Q. Succinyl CoA is used for what purposes?(Page 275)

A. Oxidation in TCA cycle, heme synthesis, andactivation of acetoacetate.

Q. What is the function of biotin? (Page 275)A. Carboxylation reactions.

Q. Name some reactions dependent on biotin.(Page 275)

A. Acetyl CoA carboxylase, propionyl CoAcarboxylase, and pyruvate carboxylase.

Q. What is the antagonist for biotin? (Page 276)A. Avidin.

Q. What is its use in laboratory? (Page 276)A. Biotin-avidin reaction is used in immunosorbent

assays.

Q. What is the chemical nature of folic acid?(Page 276)

A. Pteroyl glutamic acid (pteridine + PABA + gluta-mic acid).

Q. What is PABA? (Page 276)A. Para amino benzoic acid.


Q. What is the co-enzyme form of folic acid?(Page 276)

A. Tetrahydro folic acid.

Q. What is the main function of folic acid?(Page 276)

A. Tetrahydro folic acid is the carrier of one carbonunits.

Q. What are the causes of folate deficiency?(Page 277)

A. Pregnancy, defective absorption (sprue, celiacdisease), anticonvulsant drugs (hydantoin,dilantin, phenytoin, phenobarbitone), hemolyticanemias, and dietary deficiency.

Q. What is the major manifestation of folic aciddeficiency?

A. Macrocytic anemia. (Page 277)

Q. Folic acid deficiency in pregnancy is associatedwith what? (Page 277)

A. Folic acid deficiency during pregnancy may leadto neural tube defects in the fetus. Folic acidprevents birth defects (fetal malformations suchas spina bifida).

Q. What are the other minor effects of folic acid?(Page 277)

A. Folic acid is also useful to reduce the level ofhomo-cysteine in blood, and therefore helps inpreventing heart diseases. Folic acid is beneficialin prevention of cancer.

Vitamin-II 183

Q. What are the laboratory findings in folic aciddeficiency? (Page 278)

A. (1) Normal folic acid level in serum is decreased.(2) FIGLU is excretion is more, especially afterhistidine load. (3) AICAR excretion in urine. (4) Peri-pheral blood picture shows macrocytic anemia. (5)Homocysteine level in blood is increased

Q. What are the sources of folic acid? (Page 278)A. Yeast, liver, egg, green leafy vegetables, cereals,

and pulses.

Q. What is the daily requirement of folic acid?(Page 278)

A. The RDA of free folate is 200 mg/day. In pregnancythe requirement is increased to 400 mg/day.

Q. What is the mechanism of action of sulphona-mides? (Page 278)

A. They are anti-bacterial agents. They have struc-tural similarity with PABA. Therefore they com-petitively inhibit the enzyme responsible for theincorporation of PABA into folic acid.

Q. What is the mechanism of action of trime-thoprim? (Page 278)

A. It inhibits the folate reductase and so formationof THFA is reduced. It is bactericidal agent.

Q. What is mechanism of action of methotrexate?(Page 278)

A. It inhibits folate reductase, and is a powerfulanticancer drug.

Q. What are inhibitors of folic acid? (Page 278)A. Methotrexate, trimethoprim, pyrimethamine and

sulphonamide.


Q. Name a water soluble Vitamin, which is storedin the body.


Q. What is the metal present in Vitamin B12?(Page 279)

A. Cobalt.

Q. What is the ring system present in Vitamin B 12?(Page 279)

A. Corrin ring.

Q. Vitamin B12 is absorbed from where?(Page 279)A. Ileum.

Q. What is the transport form of Vitamin B12?(Page 279)

A. Methyl B 12.

Q. What is the carrier of Vitamin B12 in blood?(Page 279)

A. Transcobalamin-II, a glycoprotein, is the specificcarrier.

Q. What is the storage form of Vitamin B12?(Page 279)

A. It is stored in the liver cells, as ado-B12 form, incombination with transcobalamin-I or transcorrin.

Q. What is the co-enzyme function of Vitamin B 12?(Page 279)

A. Methyl malonyl CoA isomerase, andhomocysteine methyl transferase.

Vitamin-II 185

Q. What abnormalities are seen in Vitamin B 12deficiency? (Page 280)

A. Methyl malonic aciduria, accumulation of methylmalonic acid, breakdown of myelin sheaths andinterruption in nerve transmission. Homocystein-uria is also seen.

Q. What abnormal compound is excreted in VitaminB12 deficiency?

A. Methyl malonic acid in urine. (Page 280)

Q. What is folate trap? (Page 280)A. The production of methyl THFA is an irreversible

step. Therefore, the only way for generation of freeTHFA is methyl THFA to THFA, by a VitaminB12 dependent step. When B12 is deficient, thisreaction cannot take place. This is called themethyl folate trap.

Q. What is the clinical importance of folate trap?(Page 280)

A. This leads to the associated folic acid scarcity inB12 deficiency.

Q. What is the explanation of demyelination inVitamin B12 deficiency?

A. In Vitamin B12 deficiency, there is non-avail-ability of active methionine. Therefore, methyla-tion of phosphatidyl ethanolamine to phospha-tidyl choline is not adequate. This leads todeficient formation of myelin sheaths of nerves.

(Page 280)


Q. What are the causes of B12 deficiency?(Page 280)

A. Nutritional B12 deficiency, decrease in absorp-tion, addisonian pernicious anemia, atrophy ofgastric epithelium, and pregnancy.

Q. What is the cause for pernicious anemia?(Page 280)

A. It is an autoimmune disease with a strong familialbackground. Antibodies are generated againstintrinsic factor. So IF is deficient, leading todefective absorption of B12.

Q. What are the manifestations of Vitamin B12 de-ficiency? (Page 280)

A. Megaloblastic anemia and subacute combineddegeneration.

Q. What is the difference in folate deficiency andB12 deficiency?

A. In folate deficiency, there is macrocytic anemia,and in B12 deficiency, there is additionalneurological symptoms also. (Page 280)

Q. What is the daily requirement of Vitamin B12?(Page 280)

A. One to two microgram/per day.

Q. A patient who has undergone gastrectomy islikely to develop deficiency of which Vitamin?

(Page 280)A. Vitamin B12.

Vitamin-II 187

Q. In Vitamin B12 deficiency, what are the abnorma-lities seen in urine?

A. Urine may contain methyl malonic acid, homo-cystine, cystathione, and formimino glutamic acid.

(Page 280)

Q. Which is the Vitamin totally absent in plantsources?


Q. What are the sources of Vitamin B12?(Page 280)A. Liver, meat, fish, and curd.

Q. What is the chemical structure of Vitamin C?(Page 282)

A. L-ascorbic acid.

Q. How it is synthesised? (Page 282)A. Man and primates cannot synthesise ascorbic

acids. Lower animals could synthesise it fromglucose through glucuronic acid pathway.

Q. What are the major functions of ascorbic acid?(Page 282)

A. Ascorbic acid promotes collagen formationthrough its action on post-translationalhydroxylation of proline and lysine residues.

Q. What are the other functions of ascorbic acid?(Page 282)

A. Parahydroxy phenyl pyruvate oxidation to homo-gentisic acid, iron absorption from the intestine,reconversion of methemoglobin to hemoglobin,and adrenal steroidogenesis.


Q. Which Vitamin is required for post-translationalmodifications?

A. Ascorbic acid. (Page 282)

Q. What is the daily requirement of ascorbic acid?(Page 283)

A. 75 mg per day.

Q. Scurvy is due to the deficiency of which Vitamin?(Page 283)

A. Ascorbic acid.

Q. What are the important features of scurvy?(Page 283)

A. Hemorrhagic tendency, microcytic anemia, bonepain, bleeding gums.

Mineral Metabolism 189

Mineral Metabolism

Q. What influences absorption of calcium fromintestine? (Page 284)

A. Vitamin D, calcitriol, parathyroid hormone, phyticacid, and oxalate.

Q. What is the daily requirement of calcium?(Page 284)

A. 500 mg per day.

Q. What are the sources of calcium? (Page 284)A. Milk, egg, fish, and vegetables.

Q. What is the function of calcium ? (Page 285)A. Coagulation, neuromuscular activity, intra-

cellular messenger, activation of enzymes, andbone formation.

Q. What is the normal level of calcium in blood?(Page 285)

A. 9-11 mg /dl.


Q. Which will influence serum calcium level?(Page 285)

A. Calcitriol, calcitonin, and parathyroid hormone.

Q. How parathyroid hormone regulates calciumlevel in blood?

A. Bone resorption, increased absorption of calciumfrom intestines, and increased absorption ofcalcium from renal tubules. (Page 286)

Q. Hypocalcemia results in what clinical condition?(Page 287)

A. Tetany.

Q. What is the reason for tetany? (Page 287)A. Hypoparathyroidism.

Q. What are the features of hyperparathyroidism ?(Page 287)

A. Osteoporosis, hypercalciuria, and urinary calculi.

Q. What is the normal level of phosphorus in blood.(Page 287)

A. 3-4 mg /dl.

Q. What is the normal level of sodium in blood ?(Page 289)

A. 136-145 mEq/L.

Q. What is the important extracellular cation?(Page 289)

A. Sodium.

Q. Which will control the sodium level in serum?(Page 289)

A. ADH, aldosterone, and cortisone.


Q. What is the normal level of potassium in blood ?(Page 289)

A. 3.5 to 5 mEq /L.

Q. What is the major intracellular cation?(Page 289)A. Potassium.

Q. What is the manifestation of hypokalemia?(Page 289)

A. In ECG, T wave inverted, ST segment is lowered.

Q. What is the normal level of chloride in blood ?(Page 290)

A. 96- 106 mEq /L.

Q. What is the daily requirement of iron for anormal adult male ?

A. 10-20 milligram per day. (Page 291)

Q. What are the dietary sources of iron ? (Page 291)A. Green leafy vegetables, meat, and jaggery.

Q. Which is the trace element, deficient in milk?(Page 291)

A. Iron.

Q. What are important iron containing proteins?(Page 291)

A. Hemoglobin, myoglobin, cytochromes, catalase,tryptophan pyrrolase, xanthine oxidase,transferrin, and ferritin.

Q. Which will increase iron absorption fromintestines? (Page 291)

A. Gastric HCl, ascrobic acid, and cysteine.


Q. What are the factors which will retard ironabsorption? (Page 291)

A. Phytic acid (in cereals) oxalic acid (in leafyvegetables), calcium, zinc, lead and phosphates.

Q. Iron is absorbed from which part? (Page 292)A. Upper part of duodenum.

Q. How is iron absorbed? (Page 292)A. Iron in the intestinal lumen enters the mucosal

cell in the ferrous state. This is bound to transferrinmolecule present in brush border surface ofintestinal cell. One transferrin molecule can bindwith two atoms of iron. This is then complexedwith a specific receptor. This iron-transferrin-receptor is internalised.

Q. How iron absorption is regulated? (Page 292)A. Iron metabolism is unique because homeostasis is

maintained by regulation at the level of absorptionand not by excretion. When iron stores in the bodyare depleted, absorption is enhanced. Whenadequate quantity of iron is stored, absorption isdecreased. This is referred to as �mucosal block�of regulation of absorption of iron.

Q. What is the carrier protein in iron in blood?(Page 292)

A. Transferrin.

Q. Which enzyme will help in iron carriage inblood? (Page 292)

A. Ferroxidase (ceruloplasmin).


Q. What is the storage form of iron? (Page 293)A. Ferritin.

Q. What is hemosiderin? (Page 293)A. Excess iron is loaded as hemosiderin.

Q. What is haptoglobin? (Page 293)A. It is the carrier of free hemoglobin.

Q. What is hemopexin? (Page 293)A. It is the carrier of free heme.

Q. Anemia is resulted in the deficiency of whichsubstances? (Page 293)

A. Iron, copper, vitamin C, folic acid, vitamin B12,and pyridoxal phosphate.

Q. Iron deficiency results in what? (Page 294)A. Microcytic hypochromic anemia.

Q. What are the features of hemosiderosis?(Page 294)

A. Cirrhosis of liver, diabetes mellitus, and yellowcolour of skin.

Q. What is the cause for hemosiderosis? (Page 294)A. Repeated transfusion of whole blood.

Q. What are the important copper containingenzymes? (Page 294)

A. Ceruloplasmin, cytochrome oxidase, cytochromeC, tyrosinase, lysyl oxidae, and super oxidedismutase.

Q. What are dietary sources of copper? (Page 294)A. Cereals, meat, and liver.


Q. What is ceruloplasmin? (Page 294)A. It is ferroxidase, and it promotes oxidation of

ferrous ion to ferric form.

Q. What are the characteristic features of Wilson�shepatolenticular degeneration? (Page 295)

A. Ceruloplasmin level in blood is decreased, copperexcretion is reduced, and copper is accumulatedin liver to produce cirrhosis.

Q. What is the daily requirement of iodine?(Page 295)

A. 150-200 microgram.

Q. What is the daily requirement of zinc?(Page 296)

A. 15-20 milligram.

Q. What are the important enzymes which containzinc? (Page 296)

A. Alkaline phosphatase, amylase, carbonicanhydrase, and RNA polymerase. Zinc is requiredfor insulin secretion.

Q. What is Fluorosis? (Page 297)A. It is produced when fluoride concentration in

water is more than 20 ppm. Osteoporosis is themanifestation.

Q. What is the importance of selenium? (Page 298)A. It is an anti-oxidant.

Q. Name the selenium containing enzyme.(Page 298)

A. Glutathione peroxidase.

Energy Metabolism and Nutrition 195

Energy Metabolismand Nutrition

Q. What is the calorific value of carbohydrates?(Page 299)

A. Four kilocalories per gram.

Q. What is the calorific value of fats? (Page 299)A. Nine kilocalories per gram.

Q. How much calories are generated per gram of fat? (Page 299)

A. kCal.

Q. What is the respiratory quotient? (Page 299)A. It is the ratio of carbon dioxide produced to the

oxygen consumed.

Q. What is the respiratory quotient of carbohyd-rates? (Page 299)

A. One.


Q. What is the respiratory quotient for a mixed diet?(Page 299)

A. About 0.82.

Q. What is specific dynamic action? (Page 300)A. Increased heat production after intake of food.

Q. Which foodstuff has maximum specific dynamicaction ?

A. Proteins. (Page 300)

Q. Basal metabolic rate is increased in whichconditions? (Page 300)

A. Fever, starvation, cold climate, and increasedthyroid hormones.

Q. Increased basal metabolic rate is observed inwhich clinical condition?

A. Grave�s disease (hyperthyroidism). (Page 300)

Q. What are the beneficial effects of dietary fibre?(Page 301)

A. Increased motility of intestine, decreasedabsorption of cholesterol, and increased glucosetolerance.

Q. Name an undigestible carbohydrate. (Page 301)A. Pectin.

Q. Which food stuffs contain polyunsaturated fattyacids? (Page 302)

A. Vegetable oils, sunflower oil, and groundnut oil.

Q. Name essential fatty acids. (Page 302)A. Linoleic acid, linolenic acid, and arachidonic acid.

Energy Metabolism and Nutrition 197

Q. What is the dietary advice for a patient withhypercholesterolemia?

A. They should take polyunsaturated fatty acids.(Page 302)

Q. What foodstuffs contain cholesterol? (Page 302)A. Egg, butter, ghee, and pig fat.

Q. A patient with coronary artery disease is advisedto refrain from what?

A. Egg. (Page 302)

Q. What is the recommended daily allowance ofprotein of a normal adult? (Page 303)

A. 1 g/kg.

Q. Negative nitrogen balance is observed in whichconditions?

A. Chronic infection, old age, and malnutrition.(Page 303)

Q. Positive nitrogen balance is observed in whichconditions?

A. Pregnancy, convalescence, and growth period.(Page 303)

Q. Lysine is deficient in which foodstuff?(Page 305)

A. Pulses.

Q. Phenyl alanine is deficient in which food stuff?(Page 305)

A. Tapioca.

Q. Methionine is deficient in which food stuff?(Page 305)

A. Cereals.


Q. How all amino acids are made available in a mixeddiet?

A. Supplementation by combining cereals and pulses.(Page 305)

Q. What are the salient features of Kwashiorkor?(Page 305, 306)

A. Hypoalbuminemia, hypomagnesemia, growthretardation, lethargy, and loss of appetite.

Q. How much energy is required for a 60 kg person,with sedentary work?

A. 2000 kCal. (Page 307)

Q. A balanced diet should have calories forcarbohydrate, proteins and fats in which ratio?

(Page 307)A. 60:20:20.

Acid Base Balance and pH 199

Detoxification andBiotransformationof Xenobiotics

Q. What is detoxification process? (Page 310)A. Biochemical processes whereby noxious

substances are rendered less harmful or morewater soluble and easily excretable.

Q. What are xenobiotics? (Page 310)A. They are compounds accidentally ingested or

taken as drugs or compounds produced in thebody by bacterial metabolism.

Q. Give an example of a substance detoxified byreduction. (Page 311)

A. Para nitro phenol.

Q. Give examples of substances detoxified byhydrolysis. (Page 311)

A. Acetanilide to aniline + acetate, aspirin to salicylicacid + acetate.

Detoxification and Biotransformation of Xenobioticsn 199


Q. Give names of conjugating agents. (Page 311)A. PAPS, UDP glucuronic acid, glutathione, and

glycine.

Q. Give some examples of substances detoxified byconjugation.

A. Bilirubin to bilirubin glucuronide, phenol tophenyl sulfate, and benzoic acid to hippuric acid.

(Page 311)

Q. Which amino acids are used for detoxification?(Page 311)

A. Glutamine, glycine, and cysteine.

Q. Give examples of substances detoxified bysulfation. (Page 311)

A. Phenol to phenyl sulfate, and indole to indoxylsulfate.

Q. What is the sulfating agent? (Page 311)A. PAPS (phospho adenosyl phospho sulfate).

Q. How benzoic acid is detoxified? (Page 311)A. Benzoic acid + glycine = benzoyl glycine or

hippuric acid.

Q. How epinephrine is excreted? (Page 312)A. As methyl conjugates.

Q. What is the methylating agent? (Page 312)A. S-adenosyl methionine.


Q. What is the most common environmentalpoison? (Page 314)

A. Lead.

Q. What are common causes of lead poisoning?(Page 314)

A. Paint, lead containig petrol, lead pipes, news-papers, xerox copies and cigarette smoke areimportant contaminants.

Q. What are the occupations in which persons areprone to get lead poisoning? (Page 314)

A. Battery repair, radiator repair, soldering, paint-ing and printing.

Q. What is the toxic level of lead? (Page 314)A. Blood level of lead, more than 10 ?g/dl in children

and more than 25 ?g/dl in adults lead to toxicmanifestations.

BiochemicalAspects ofEnvironmental Pollution

Biochemical Aspects of Environmental Pollution 201


Q. What are the manifestations of chronic leadpoisoning? (Page 314)

A. Miscarriage, stillbirth, and premature birth. Inchildren, mental retardation, learning disabilities,behavioral problems, hyperexcitability andseizures are seen. Anemia, abdominal colic andloss of appetite are very common.

Q. What are the manifestation of acute lead poisoning?(Page 314)

A. Encephalopathy, convulsions, mania, neuropathy,abdominal colic, severe anemia and kidneydamage, discolouration and blue line along thegums.

Q. When does acute toxicity is manifested?(Page 314)

A. If the blood level of lead is more than 70 mg/dl,acute toxicity is manifested.

Q. What is the cause of anemia in lead poisoning?(Page 314)

A. Lead inhibits delta amino levulinic acid (ALA)synthase, ALA-dehydratase and ferrochelatase.So, heme synthesis is blocked. Life span of RBCis shortened. Anemia enhances lead absorption,lead in turn produces more anemia, thus a viciouscycle is operating.

Q. What are the antidotes for lead poisoning?(Page 314)

A. Calcium dodecyl edetate (Calcium disodiumversenate), penicillamine and dimercaprol (BAL)are used as antidotes. Dimercaptosuccinic acid isa better but costly antidote.


Q. What is the pH of 0.1 M hydrochloric acid?(Page 319)

A. One.

Q. When pH falls by 1 unit, what is the change inthe hydrogen ion concentration? (Page 319)

A. Increases by 10 times.

Q. Relationship between pH and pK is given bywhich equation? (Page 320)

A. Henderson-Hasselbalch�s equation.

Q. What determines the pH of buffer? (Page 320)A. By the ratio of salt to acid.

Q. Buffer is most effective when? (Page 320)A. When pK of the acid is nearer to pH.

Q. When is the buffering capacity is more?(Page 320)

A. When the absolute concentrations of salt and acidare more.

Acid BaseBalance and pH


Q. In the blood, which buffer is most effective?(Page 321)

A. Bicarbonate buffer.

Q. What are the mechanisms for maintaining thenormal pH of plasma? (Page 321)

A. Buffers of plasma, lung mechanism, and kidneymechanism.

Q. What is the alkali reserve of the body?(Page 321)

A. Bicarbonate is the alkali reserve.

Q. What is the ratio of bicarbonate to carbonic acidin blood? (Page 321)

A. Bicarbonate to carbonic acid ratio is 20.

Q. What are the mechanisms by which renalregulation of acid load is achieved? (Page 323)

A. Excretion of hydrogen ions in urine, excretion ofammonium ions in urine, and production ofbicarbonate in renal tubules.

Q. Glutaminase enzyme is used for what purpose?(Page 323)

A. For production of ammonia in kidney tubules.

Q. What is metabolic acidosis? (Page 325)A. Primary deficit of bicarbonate.

Q. What are the causes of metabolic acidosis?(Page 326)

A. Diabetic ketosis, chronic renal failure, anddiarrhea.


Q. What are the features of diabetic ketoacidosis?(Page 326)

A. Lowered bicarbonate, elevated plasma chloride,and increased anion gap.

Q. What is the formula used to calculate anion gap?(Page 326)

A. (sodium + potassium) minus (chloride +bicarbonate).

Q. What is the cause for high anion gap acidosis?(Page 326)

A. Diabetic ketoacidosis, chronic renal failure, renaltubular acidosis, lactic acidosis.

Q. What is metabolic alkalosis? (Page 326)A. Primary excess of bicarbonate.

Q. What are the causes of metabolic alkalosis?(Page 326)

A. Prolonged vomiting, gastric aspiration, andingestion of antacids.

Q. What is respiratory acidosis? (Page 326)A. Primary excess of carbonic acid.

Q. What are the causes of respiratory acidosis?(Page 327)

A. Bronchial asthma, bronchopneumonia, andnarcotic poisoning.

Q. What is respiratory alkalosis? (Page 327)A. Primary deficit of carbonic acid.


Q. What is the cause for respiratory alkalosis?(Page 327)

A. Hyperventillation.

Q. What are the results of prolonged vomiting?(Page 327)

A. Alkalosis, hypochloremia, and hypokalemia.

Molecular Biology I 207

Electrolyte andWater Balance

Q. What is the major intracellular cation?(Page 329)A. Potassium.

Q. What is the major extracellular cation?(Page 329)A. Sodium.

Q. What is the function of anti diuretic hormone?(Page 330)

A. Its secretion is stimulated when plasmaosmolarity increases, ADH decreases the urineoutput, and retains water in the body.

Q. What are the factors regulating fluid andelectrolyte balance?

A. Aldosterone and anti diuretic hormone.(Page 330)

Q. What are the diuretic drugs used? (Page 330)A. Aldosterone antagonists, angiotensin converting

enzyme inhibitors, and carbonic anhydraseinhibitors.

Electrolyte and Water Balance 207


Q. What is the major cause for isotonic contractionof ECF? (Page 331)

A. Small intestinal obstruction.

Q. What are the causes for hypotonic contraction ofECF? (Page 331)

A. Infusion of dextrose (without saline), Addison�sdisease.

Q. What are the causes for hypertonic contractionof ECF? (Page 331)

A. Diarrhoea, vomiting.

Q. What are the causes for isotonic expansion ofextracellular fluid?

A. Congestive cardiac failure andhyperaldosteronism. (Page 331)

Q. What is the cause for hypotonic expansion ofextracellular fluid?

A. Inappropriate secretion of ADH. (Page 331)

Q. What is the important cause for hypertonicexpansion of ECF?

A. Cushing�s syndrome. (Page 331)

Q. What are the metabolic imbalances seen indiarrhea? (Page 331)

A. Metabolic acidosis, hypertonic contraction of ECF,urine with high specific gravity, and urine outputreduced.


Q. What is a nucleotide? (Page 332)A. Nitrogenous base + sugar + phosphate.

Q. What is a nucleoside? (Page 332)A. Nitrogenous base + sugar.

Q. What are the sugars? (Page 332)A. Ribose in RNA and deoxyribose in DNA.

Q. What are the bases present in nucleotides?(Page 332)

A. Purines and pyrimidines.

Q. Name the common purines. (Page 332)A. Adenine and guanine.

Q. Name the common pyrimidines. (Page 332)A. Cytosine, uracil, and thymine.

Molecular Biology-I:Nucleotides, Chemistryand Metabolism


Q. What are the bases present in DNA? (Page 332)A. Adenine, guanine, cytosine, and thymine.

Q. Which nitrogenous base is absent in DNA?(Page 332)

A. Uracil.

Q. Which base is found exclusively in DNA and notin RNA? (Page 332)

A. Thymine.

Q. Which base is found exclusively in RNA and notin DNA? (Page 332)

A. Uracil.

Q. Which amino acid is required for both purineand pyrimidine synthesis? (Page 333)

A. Aspartic acid and glutamine.

Q. N3 of purine ring is donated by what?(Page 335)A. Glutamine.

Q. Glycine donates what part of the purine ring?(Page 335)

A. C4, C5, N7 atoms.

Q. N1 atom of purine ring is coming from what?(Page 335)

A. Aspartic acid.

Q. One carbon pool donates which carbon atomsof purine ring?

A. C2 and C8 carbon atoms. (Page 335)


Q. What is the key enzyme of de novo synthesispathway of purines? (Page 337)

A. The committed step in de novo synthesis is thereaction catalysed by amidotransferase (step 1).

Q. How is de novo synthesis of purine regulated?(Page 337)

A. Amidotransferase enzyme is inhibited by AMPand GMP.

Q. What are the enzymes needed for salvagepathway of purines? (Page 337)

A. Adenine phospho ribosyl transferase (APRTase)and hypoxanthine guanine phospho ribosyltransferase (HGPRTase).

Q. What is the importance of the salvage pathway?(Page 337)

A. This is of special importance in tissues like RBCsand brain where the de novo pathway is notoperating.

Q. What is the clinical significance of the purineanalogues? (Page 338)

A. They act as cell cycle inhibitors and can be usedas anti-cancer drugs.

Q. Give a few examples of purine analogues, usedas anti-cancer drugs. (Page 338)

A. 6-mercapto-purine inhibits the conversion of IMPto GMP and AMP. 2. Cytosine arabinoside. 3.Folate antagonists (Methotrexate) would affect thereactions involving one carbon group transfers.4. Azaserine is a glutamine antagonist andtherefore inhibits reactions involving glutamine.


Q. What is the end product of catabolism of purinesin human beings?

A. Uric acid. (Page 338)

Q. What is xanthine oxidase? (Page 338)A. It is the enzyme for the reactions, hypoxanthine

to xanthine and xanthine to uric acid.

Q. What is the speciality in this reaction?(Page 338)A. Xanthine oxidase is a metalloflavoprotein con-

taining FAD, molybdenum and iron. As xanthineis oxidised to uric acid, hydrogen peroxide(reactive oxygen species) is produced.

Q. What is the normal uric acid level in blood?(Page 338)

A. The normal blood level of uric acid ranges from2-5 mg/dl in females and 3-7 mg/dl in males.

Q. What is the normal excretion rate of uric acid?(Page 338)

A. The daily excretion of uric acid varies from 500-700 mg.

Q. Which property of uric acid is responsible forthe manifestations of gout? (Page 338)

A. Uric acid is sparing soluble in water.

Q. Increased uric acid level is seen in which condi-tions? (Page 339)

A. Gout, pre-eclampsia, Hodgkin�s lymphoma,leukemia, and diabetic ketoacidosis.


Q. Hyperuricemia can result from defect of whichenzymes? (Page 339)

A. Ribosyl amido transferase, PRPP synthetase,HGPRTase, APRTase, Glucose-6-phosphatase,and glutathione reductase.

Q. Hyperuricemia is observed in which conditions?(Page 339)

A. Gout, Lesch Nyhan syndrome, von Gierke�sdisease.

Q. What are salient features of Lesch-Nyhansyndrome? (Page 340)

A. Self mutilation, hyperuricemia, and X-linkedinheritance.

Q. What is the mechanism of action of allopurinol?(Page 340)

A. It is an analogue of hypoxanthine. It inhibitsxanthine oxidase, and thereby decreasing theformation of uric acid.

Q. It is what type of inhibition? (Page 340)A. Xanthine oxidase converts allopurinol to

alloxanthine. It is a more effective inhibitor ofxanthine oxidase. This is a good example of�suicide inhibition.

Q. Hypouricemia can result from deficiency ofwhich enzyme? (Page 340)

A. Adenosine deaminase deficiency.

Q. How is it manifested? (Page 340)A. Severe immunodeficiency.


Q. What are used for pyrimidine synthesis?(Page 340)

A. Carbamoyl phosphate and aspartic acid.

Q. What is the rate limiting step in pyrimidinesynthesis? (Page 340)

A. Aspartyl trans carbamoylase.

Q. What is carbamoyl phosphate synthetase II andhow is it different from type I enzyme?

(Page 341)A. CPS-II is involved in pyrimidine synthesis, but

CPS-I is for urea synthesis. CPS-II is in cytosol,but CPS-I is in mitochondria. CPS-II is inhibitedby CTP, whereas CPS-I is not.

Q. How is pyrimidine synthesis pathway regulatedin mammals?

A. CPS II is inhibited by CTP. (Page 341)

Q. What is the mechanism of action of 6-mercptopurine? (Page 342)

A. It inhibits conversion of IMP to AMP, and so actsas an antimetabolite.

Q. What is the mechanism of action of 5-fluorouracil? (Page 342)

A. It inhibits conversion of dUMP to dTTP, and actsas an antimetabolite.

Q. Orotic aciduria is a feature of deficiency of whichenzymes? (Page 342)

A. OMP decarboxylase, OPRTase, and ornithinetranscarbamoylase.


Q. What are the characteristic features of oroticaciduria ? (Page 342)

A. Megaloblastic anemia, urinary tract obstruction,and response to oral uridine therapy.

Q. Formation of dTMP (thymine nucleotide)requires what enzyme and co-enzymes?

(Page 342)A. Methylation of dump is done by thymidylate

synthase. The methyl group is donated bymethylene-THFA. Later, THFA is regenerated bydihydrofolate reductase, using NADPH.Methotrexate inhibits dihydrofolate reductaseand thereby reduces the regeneration of THFA,and it is a powerful anticancer agent.

Q. How deoxyribonucleotides are formed?(Page 342)

A. By the reduction at the 2' carbon of the corres-ponding nuceloside diphosphates (NDP todNDP).

Q. What are the enzymes and co-enzymes for thisreaction? (Page 342)

A. Ribonucleotide reductase, NADPH, andthioredoxin.


Q. What are the important characteristics of Watson-Crick model of DNA? (Page 344)

A. Right-handed double helix, each turn of helix has10 base pairs, Hydrogen bonds between purinesand pyrimidines, and DNA strands running inopposite directions (anti parallel).

Q. What is base pairing rule? (Page 344)A. Pairing (hydrogen bonding) of adenine with

thymine and guanine with cytosine. Purine ispaired with pyrimidine A+T = G+C.

Q. What are the modifications seen in histones?(Page 345)

A. Acetylation, methylation, and phosphorylation.

Q. What is nucleosome? (Page 345)A. DNA wrapped around histones.

Molecular Biology-II:DNA structure and Replication

Molecular Biology-III 217

Q. What is euchromatin? (Page 346)A. Transcriptionally active chromatin is called

euchromatin. It is less densely packed, andsensitive to digestion by DNAse.

Q. What is meant by DNA replication? (Page 346)A. During cell division, each daughter cell gets an

exact copy of the genetic information of the mothercell. This process of copying the DNA is knownas DNA replication.

Q. How the exact copying is effected? (Page 346)A. Each strand serves as a template or mould, over

which a new complementary strand is synthe-sised. The base pairing rule is always maintained.

Q. What are the enzymes required for DNAreplication? (Page 347)

A. DNA polymerase, topo isomerase, and DNAligase.

Q. How many DNA polymerases are there inmammalian cells?

A. Five. Alpha, beta, gamma, delta, and epsilon.(Page 347)

Q. What a replisome? (Page 347)A. DNA replication needs the participation of more

than 20 enzymes and proteins, collectively calledDNA replicase system or replisomes.

Q. What is a replication bubble? (Page 348)A. Helicases move on both directions, separating the

strands in advance of the replication. This formsa replication bubble.

II


Q. Replication is in which direction? (Page 347)A. Polymerisation of the new strand of DNA is

taking place from 5' to 3' direction. This meansthat the template is read in the 3' to 5' direction.

Q. How replication starts? (Page 347)A. An RNA primer, about 100-200 nucleotides long,

is synthesised by the RNA primase.

Q. What is meant by semiconservative nature ofreplication? (Page 346)

A. In the daughter cell, one strand is derived fromthe mother cell, while the other strand is newlysynthesised. This is called semi-conservative typeof DNA replication.

Q. What is meant by semi-discontinuous nature ofreplication? (Page 348)

A. DNA synthesis is always in the 5' to 3' directionin both strands. Replication fork advancestowards one side. So, in one strand, the replicationis taking place continuously, but in the otherstrand replication is in small pieces.

Q. What is lagging strand? (Page 348)A. The strand which is discontinuously synthesised

is referred to as the �lagging strand� and the onecontinuously polymerised as the �leadingstrand�.

Q. What are okazaki fragments? (Page 348)A. The small DNA molecules attached to its own

primer RNA in the lagging strand are calledokazaki fragments. The RNA is removed andDNA pieces are joined by ligases.


Q. Xeroderma pigmentosum is due to deficiency ofwhat process? (Page 349)

A. Defect in DNA repair mechanism (nucleotideexcision repair).

Q. Defect in DNA repair mechanisms produce whatclinical conditions?

A. Xeroderma pigmentosum, ataxia-telangectasia,Fanconi�s anemia, and Bloom�s syndrome.

(Page 350)

Q. Which enzymes protects cellular ageing?(Page 350)

A. Telomerase.

Q. In prokaryotes, DNA replication is inhibited bywhat drugs?

A. Ciprofloxacine, nalidix acid, and novobiocin.(Page 350)

Q. DNA replication in eukaryotes is inhibited bywhat drugs? (Page 350)

A. 5-fluoro uracil, 6-mercaptopurine, cytosinearabinoside, and etoposide.

II


Q. What is transcription? (Page 351)A. The process of making a complementary mRNA

copy of DNA.

Q. The mRNA is a complementary copy of whichstrand of DNA?

A. Template strand. (Page 351)

Q. What is coding strand? (Page 351)A. The opposite strand of template strand. Coding

strand has the same sequence as of the mRNA.

Q. What is the enzyme necessary for the transcrip-tion? (Page 351)

A. DNA dependent RNA polymerase or RNAP.

Q. What are the different types of RNAP?(Page 351)

A. RNAP type II or B is the enzyme synthesisingmRNAs. RNAP type I or A is responsible forsynthesis of rRNA while type III or C isresponsible for production of tRNA.

Molecular Biology-III:Transcription and Translation


Q. What is the specific inhibitor of RNAP?(Page 352)

A. RNAP II is inhibited by alpha amanitin.

Q. What is the direction of transcription?(Page 352)A. It takes place in the 5' to 3' direction.

Q. What is TATA Box? (Page 352)A. It is a signal for initiation of transcription in

prokaryotes. It is about 10 bp upstream of startingof mRNA synthesis. It is also called pribnow box.

Q. What is the corresponding signal in mammals?(Page 352)

A. Godberg-Hogness Box. It is located at -25 to -30position.

Q. How termination of transcription is effected?(Page 353)

A. The specific signals are recognised by a termi-nation protein, the Rho factor, then the RNAPenzyme dissociates from DNA. There is also RhoIndependent Termination. This is effected by aninterrupted invert repeat in DNA. This is transcri-bed. So the mRNA makes a hairpin structure. Thisobstructs further movement of RNA.

Q. What are post-transcriptional modifications?(Page 353)

A. Removal of introns, addition of a cap at 5' end,adding poly A tail at 3' end and methylation.

Q. What are the non-coding sequences? (Page 354)A. Leader sequence, poly-A tail, introns.

Q. What is intron? (Page 354)A. Part of mRNA that is removed is called intron.


Q. What is a spliceosome? (Page 354)A. Small nuclear ribonucleoprotein particles

(SnRNPs) associated with hnRNA at the exon-intron junction form spliceosomes. This is takingplace inside the nucleus.

Q. What is the cause for systemic lupus erythe-matosis? (Page 354)

A. Production of auto antibodies against smallnuclear ribonucleoprotein particles causesystemic lupus erythematosis (SLE), a fatal auto-immune disease.

Q. What are ribozymes? (Page 354)A. Enzymes made up of RNA are called ribozymes.

Q. Give some examples of ribozymes. (Page 354)A. Spliceosomes, RNAse-P (which generates the ends

of tRNAs) and peptidyl transferase (present inribosomes) are examples of ribozymes.

Q. Give the names of inhibitors of RNA synthesis.(Page 354)

A. Rifampicin, actinomycin, mitomycin and amanitin.

Q. What is the mechanism of action of mitomycin?(Page 354)

A. Actinomycin D and mitomycin intercalate withDNA strands, thus blocking transcription. Theyare used as anticancer drugs.

Q. What is the mechanism of action of Rifampicin?(Page 354)

A. It binds to beta subunit of RNA polymerase, andinactivates it. Rifampicin is widely used in thetreatment of tuberculosis and leprosy.


Q. What is the mechanism of action of amanitin?(Page 354)

A. It inactivates RNA polymerase II.

Q. What is reverse transcriptase? (Page 354)A. In retroviruses, RNA is the genetic material (not

DNA). The RNA dependent, DNA polymerase orreverse transcriptase will make a new DNA strandbased on the RNA template. Thus, geneticinformation is transferred from RNA to DNA.

Q. Give an example of retrovirus. (Page 355)A. The human immunodeficiency virus (HIV)

causing AIDS is a retrovirus.

Q. What are the structural features of tRNAmolecule? (Page 355)

A. It has clover shape appearance. It contains unusualbases. Amino acid binding is at 3' end. The oppo-site part has anticodon arm.

Q. During protein synthesis, amino acid sequenceis specified by what?

A. The codons present in messenger RNA.(Page 355)

Q. During replication, DNA is synthesised in whichdirection? (Page 356)

A. From 5' to 3' direction.

Q. During transcription, mRNA is synthesised inwhich direction?

A. From 5' to 3' direction. (Page 356)


Q. During translation, protein is synthesised inwhich direction?

A. From amino terminal end to carboxy terminal end.(Page 356)

Q. What are the salient features of genetic code?(Page 356)

A. Triplet codons are consecutive three bases pairsin mRNA. The codons are non-overlapping,degenerate, but unambiguous and universal.

Q. What is meant by degeneracy of genetic code?(Page 356)

A. One amino acid is represented by multiple codons.

Q. What is meant by the term wobbling?(Page 357)A. Anticodons pair with codons that differ at the

third base.

Q. What is the initiating codon for protein synthesis?(Page 357)

A. AUG.

Q. What is Shine-Dalgarno sequence? (Page 357)A. Marker of start signal for translation in bacterial

mRNA.

Q. Where is protein biosynthesis taking place?(Page 358)

A. Ribosomal assembly either attached to endoplas-mic reticulum, or in cytoplasm.

Q. How many high energy bonds are required forthe synthesis of one peptide bond? (Page 359)

A. Four high energy bonds.


Q. Give examples of diseases caused by proteintargetting defects.

A. Zellweger syndrome, adrenoleukodystrophy andprimary hyperoxaluria. (Page 360)

Q. What is the function of signal peptide?(Page 360)

A. Causes anchorage of ribosome to endoplasmicreticulum, and so directs the new protein into theendoplasmic reticulum. Such proteins are des-tined for secretion.

Q. What is the location of signal peptide?(Page 360)

A. In the amino terminal region of the nascent protein.

Q. What is the location of the address for destinationof proteins?

A. These are in the carboxy terminal end of proteins.(Page 360)

Q. Give examples for post-translational modifications.(Page 361)

A. Gamma carboxylation of prothrombin, hydroxy-lation of proline in collagen, methylation ofhistones, and glycosylation of proteins.

Q. Give examples of diseases produced by defectin post-translational modifications. (Page 361)

A. Lathyrism, Ehlers-Danlos syndrome, and scurvy.

Q. Give examples of inhibitors of translation ineukaryotic cells?

A. Puromycin, cycloheximide, diphtheria toxin, andricin. (Page 361)


Q. What is the mechanism of action of erythromycin?(Page 361)

A. Inhibition of translocation in prokaryotes.

Q. What is the mechanism of action of tetracycline?(Page 361)

A. Inhibition of tRNA binding to ribosome in bacteria.

Q. What is the mechanism of action of streptomycin?(Page 361)

A. Misreading of codes and inhibition of initiationcomplex formation in bacteria.

Q. What is the mechanism of action of chloram-phenicol? (Page 361)

A. Inhibition of peptidyl transferase in bacteria.

Q. Give examples of reversible inhibitors of proteinsynthesis in bacteria.

A. These antibiotics are bacteriostatic. Tetracyclins,chloramphenicol, erythromycin and clindamycinare examples. (Page 361)

Q. Give an example of irreversible inhibitor of pro-tein synthesis in bacteria. (Page 361)

A. These antibiotics are bactericidal. Streptomycinis an example.

Q. Leber�s hereditary optic neuropathy is due towhat? (Page 362)

A. Due to mutation in mitochondrial DNA.

Molecular Biology-V 227

Q. Give examples of X-chromosome linked trans-mission. (Page 364)

A. Hemophilia, glucose-6-phsophate dehydrogenasedeficiency, and duchenne type muscular dystrophy.

Q. What is a mutation? (Page 366)A. An alteration in the genetic material results in a

mutation.

Q. Give an example. (Page 366)A. HbS or sickle-cell hemoglobin is produced by a

mutation of the beta chain in which the 6th positionis changed to valine, instead of the normalglutamate.

Q. What type of mutation is it? (Page 366)A. Here, the normal codon GAG is changed to GUG

(transversion).

Molecular Biology-IV:Molecular Genetics andControl of Gene Expression

Molecular Biology-IV 227


Q. Give an example for an unacceptable mutation.(Page 366)

A. Haemoglobin M.

Q. Give examples for mutagens. (Page 367)A. Acridine orange, X-rays, gamma rays, and methyl

cholanthrene.

Q. How mutagenecity of a compound is tested?(Page 367)

A. By Ame�s test.

Q. In which phase of the cell cycle, DNA synthesisis maximum?

A. S phase. (Page 368)

Q. What is the p53? (Page 368)A. It is an oncosuppressor gene product.

Q. Give examples of enzyme induction. (Page 370)A. Beta galactosidase by lactose, tryptophan

pyrrolase by glucocorticoid and ALA synthase bybarbiturates.

Q. Give an example of repression. (Page 370)A. ALA synthase by heme.

Q. Give names of some important antiviral drugs.(Page 371)

A. Acyclovir, Ribavirin, Zidovudine.

Q. What is a prion? (Page 372)A. �Prions� is the acronym for �proteinaceous

infective particles�.


Q. What are the uses of recombinant DNAtechnology? (Page 374)

A. Quantitative preparation of bio-molecules,especially human proteins. Risk of contaminationis eliminated, when preparing such biomolecules.Specific probes for diagnosis of diseases can beprepared. It is used in gene therapy.

Q. What are restriction endonucleases? (Page 374)A. Restriction endonucleases are referred to as

�molecular scissors�. These enzymes recognisespecific sequence with palindrome arrangementin the double stranded DNA, and then cleave atthose sites. They are useful in recombinant DNAtechnology.

Q. What are required for preparing a recombinantDNA molecule?

A. Restriction endonuclease, plasmid vector, andDNA ligase. (Page 375)

Molecular Biology-V:Recombinant DNATechnology and Gene Therapy


Q. How are DNA fragments separated? (Page 378)A. Agarose gel electrophoresis.

Q. What is Southern blotting? (Page 378)A. DNA is isolated, fragmented by restriction

endonucleases, cut pieces are electrophoresed inagarose gel, then blotted over to a nitrocellulosemembrane, when single-stranded DNA will beadsorbed in the nitrocellulose membrane. Theradio active probe is placed over the membrane.The membrane is then thoroughly washed andautoradiographed.

Q. What is the use of Southern blotting?(Page 378)A. To identify abnormal genes, to demonstrate virus

integration, prenatal diagnosis.

Q. Give some examples of genetic diseases thatcould be identified by Southern blotting.

(Page 379)A. Sickle cell anemia, Huntington�s chorea,

Duchenne muscular dystrophy.

Q. What is Northern blotting? (Page 379)A. The Northern blot is used to demonstrate specific

RNA.

Q. What is Western blotting? (Page 379)A. In this technique, proteins (not nucleic acids) are

identified. The proteins are isolated from thetissue and electrophoresis is done. The separatedproteins are then transferred on to a nitrocellulosemembrane. After fixation, it is probed withradioactive antibody and auto-radiographed.


Q. What is meant by the term cloning? (Page 379)A. The term cloning has two broad meanings. When

a gene of higher organism is introduced into abacterial DNA, it is called �cloning of the gene�or �molecular cloning�. When a cell from ananimal is grown to an exact duplicate of thatanimal, it is known as �cloning of an animal� or�somatic cloning�.

Q. What are the applications of cloning of animals?(Page 379)

A. Animals with genetically desirable traits could bebred more efficiently, e.g. cows yielding moremilk. Cows or goats may be genetically engineeredto produce milk containing any human protein.

Q. RFLP (restriction fragment length polymorp-hism) is used for what?

A. Locating mutations in DNA. (Page 381)

Q. What is the application of DNA fingerprinting?(Page 381)

A. It has medico-legal application.

Q. What are the vectors used for gene therapy?(Page 381)

A. Retrovirus, adenovirus, and plasmid liposomecomplex.

Q. Give some diseases in which gene therapy isused successfully?

A. Severe combined immuno deficiency, duchennemuscular dystrophy, cystic fibrosis, familialhypercholesterolemia, and hemophilia.(Page 382)


Q. What is transgenesis? (Page 383)A. It is a form of germ cell gene therapy. A

recombinant DNA segment, containing thedesired gene from another species, is introducedinto the fertilized ova. The embryos are allowedto develop in the uterus of another animal.

Q. What is the technique used for gene amplifi-cation? (Page 384)

A. Polymerase chain reaction.

Q. Which enzyme is required for PCR (polymerasechain reaction)?

A. Taq polymerase. (Page 384)

Q. What is reverse PCR? (Page 384)A. This allows cDNA synthesis from mRNA

followed by PCR amplification. In ordinary PCR,DNA is detected, that DNA could be from a livingor non-living organism. But in reverse PCR,mRNA is detected, that means, it is derived froma living organism.

Q. What is the use of PCR? (Page 384)A. Diagnosis of bacterial and viral diseases,

medicolegal cases, diagnosis of genetic disorders,especially prenatal diagnosis. Only very minutequantity of sample is required.

Clinical Biochemistry-III 233

Q. What is the full form of AIDS? (Page 387)A. Acquired immuno deficiency syndrome.

Q. What is the causative organism of AIDS?(Page 387)

A. Human immunodeficiency virus.

Q. How can you detect window period of thedisease? (Page 387)

A. In the window period viral capsid antigen (p24)can be detected

Q. What are the usual laboratory findings in thediagnosis of AIDS?

A. The antibodies against gp120 are detected by theELISA test. To rule out the false positive test, theELISA positive blood, is then retested withWestern blot analysis. (Page 388)

Biochemistry of AIDS

Biochemistry of AIDS 233


Q. What other special tests could be done?(Page 388)

A. T-helper cell count is below 300/ cu.mm. ByRTPCR (reverse transcriptase polymerase chainreaction, the number of HIV particles in blood canbe estimated, a value of less than 5000 copies perml of blood has good prognosis, while a countmore than 1 lakh per ml means very bad prognosis.

Q. HIV belongs to which group of virus?(Page 388)A. It is a retrovirus. It is an RNA virus.

Q. What is the characteristic of retrovirus?(Page 388)

A. It contains the enzyme reverse transcriptase.

Q. How the virus gets entry into the tissue cells?(Page 388)

A. The gp 120 of the virus envelope will specificallybind with CD4 molecules on the surface of targetcells. CD4 acts as a receptor for the virus.

Q. Where is CD4 molecules present? (Page 388)A. The CD4 molecules are present on the surface of

T-helper cells.

Q. What are the major groups of anti-HIV drugsavailable? (Page 390)

A. Reverse Transcriptase (RT) inhibitors andprotease inhibitors.

Q. How RT inhibitors are classified? (Page 390)A. nucleoside analogues, non-nucleoside analogues

and nucleotide analogues.


Q. Name some chemical carcinogens. (Page 391)A. Methyl cholanthrene, aflatoxins, benzopyrenes.

Q. Name some physical carcinogens. (Page 393)A. X-ray, gamma-ray and UV-ray.

Q. Name some anti-mutagens and anti-carcinogens.(Page 393)

A. Vitamin A, Vitamin C, Vitamin E, and curcumin.

Q. Name some oncogenic viruses. (Page 393)A. Epstein Barr virus (EBV), hepatitis B virus(HBV),

and human papilloma virus.

Q. What are Oncogenes? (Page 394)A. Genes capable of causing cancer. Oncogenes are

specific sequences in DNA which when expressedmay produce cancer.

Q. What are proto-oncogenes? (Page 394)A. Oncogenes present in normal cells are also called

as proto-oncogenes.

Biochemistry of Cancer

Biochemistry of Cancer 235


Q. Proto-Oncogenes may be activated by whatmechanisms? (Page 395)

A. Viral infection, mutation in proto-oncogene,promoter insertion, and chromosome translocation.

Q. Name a cancer, produced by the deletion of anoncosuppressor gene?

A. Retinoblastoma. (Page 396)

Q. What are tumour markers? (Page 398)A. They are factors released from the tumour cells,

which could be detected in blood and thereforeindicate the presence of the tumour in the body.

Q. What is the clinical application of tumourmarkers? (Page 398)

A. They are useful for the following purposes. (1)For follow up of cancer and to monitor theeffectiveness of the therapy. (2) To detect therecurrence of the tumour

Q. Name some important tumour markers.(Page 399)

A. Alpha feto protein, carcino embryonic antigen,prostate specific antigen, neuron specific enolase,beta chain of human chorionic gonadotropin, andregan iso-enzyme of alkaline phosphatase.

Q. Alpha feto protein (AFP) level in serum isincreased in which condition?

A. Hepatoma. (Page 399)

Q. Carcino embryonic antigen level is increased inwhich type of cancers? (Page 399)

A. Colorectal and gastrointestinal cancers.


Q. What is the significance of beta chain of humanchorionic gonadotropin? (Page 399)

A. It is a tumour marker for choriocarcinoma.

Q. What is the mechanism of action of mitomycin?(Page 400)

A. Intercalation with DNA strands.

Q. What is the mechanism of action of Methotrexate?(Page 400)

A. It is a folic acid antagonist.

Q. What is vincristine and vinblastine? (Page 400)A. They are alkaloids from vinca rosea, they interfere

with assembly of cytoskeleton and inhibits stath-mokinesis (spindle movement), so they are usedas anti-cancer drug.

Q. What is the mechanism of action of adriamycin?(Page 400)

A. It inhibits topo-isomerase.

Biochemistry of Cancer 237


Q. What is an Isotope?

A. Isotopes of a given element will have differentatomic weights, but will have same atomicnumber.

Q. Radiation hazard is mainly due to which type ofradiation?

A. Alpha radiation.

Q. Iodine-125 emits mainly emits which type ofradiation?

A. Gamma radiation.

Q. What is the isotope used for DNA studies?

A. P-32.

Q. P-32 is used clinically for what purpose?

A. To treat polycythemia vera.

Applications ofRadio-isotopesin Medicine


Q. Which radio-active compound is used to measureglomerular filtration rate (GFR)?

A. 131-Iodine labelled hippuran.

Q. For RIA (radio immuno assay), the radio-activeisotope used is:

A. 125-Iodine.

Q. What is the use of radio active radium inmedicine?

A. Intracavity application of radiation, such ascarcinoma cervix or body of uterus.

Q. What is the common source of radiation inteletherapy?

A. 137-Cs (caesium) with a half-life of 30 years.

Q. What are radiosensitive tumours?

A. Lymphomas, Hodgkin�s disease and neuroblas-toma are highly radiosensitive.

Q. What are the important toxic effects of radiation?

A. Leukopenia, thrombocytopenia, and radiationdermatitis.

Applications of Radio-isotopes in Medicine 239


Q. How lactose is synthesised? (Page 407)A. UDP glucose is epimerased to UDP galactose.

Then the galactose unit is transferred from UDP-galactose to glucose. This synthesis of lactose inmammary gland is catalysed by lactose synthase.

Q. How lactose synthesis is regulated? (Page 407)A. The lactose synthase has two subunits, a catalytic

subunit which is a galactosyl transferase and amodifier subunit that is alpha lactalbumin. Thelevel of the modifier subunit is under the controlof prolactin.

Q. What is the major difference between humanand cow�s milk?

A. Human milk has higher carbohydrate content thancow�s milk while protein content is less.

(Page 407)

Q. How is to humanize cow�s milk? (Page 407)A. To humanise cow�s milk, protein is to be diluted

and carbohydrate is to be added. Thus, to one cupof cow�s milk, add half a cup of water and twoteaspoons of sugar. This will make it comparableto human milk.

Body Fluids


Q. Milk contains which type of fatty acids?(Page 407)

A. The fatty acids are mainly saturated, but 50% ofthem are medium chain fatty acids (Lauric andMyristic acids).

Q. What is the advantage of medium chain fattyacids? (Page 407)

A. They are easily digested, absorbed andmetabolized.

Q. What is the major protein in cow�s milk?(Page 407)

A. Eighty percent protein of cow�s milk is casein.

Q. What type of protein is casein? (Page 407)A. It is a phospho-protein.

Q. How the phosphate group is attached to protein?(Page 407)

A. The phosphate groups are added to the hydroxylgroups of serine or threonine residues.

Q. What is whey? (Page 407)A. If milk is acidified and pH lowered to 4.7, the

casein is precipitated (iso-electric precipitation).The supernatant is called whey.

Q. What are the proteins present in whey?(Page 407)

A. Lactalbumin, lactoglobulin and lysozyme.

Body Fluid 241


Q. What are G proteins? (Page 410)A. They are involved in signal transduction.

Q. How the G proteins work? (Page 410)A. The receptors are in membrane, and binding of

hormone causes activation of G protein.

Q. How is G protein activated? (Page 411)A. Binding of hormone on receptor causes

attachment of GTP to G protein, and thereby Gprotein is activated.

Q. What is the function of activated G protein?(Page 411)

A. Activated G protein activates adenyl cyclase.

Q. What is the function of adenyl cyclase?(Page 411)

A. Adenyl cyclase will produce cyclic AMP.

Q. How adenyl cyclase is destroyed? (Page 411)A. By phospho diesterase.

Hormones-I:Mechanism ofAction of Hormones


Q. How cyclic AMP further works? (Page 411)A. Cyclic AMP activates protein kinase.

Q. What is the function of protein kinase?(Page 411)

A. It phosphorylates enzymes or target proteins, sothat they are activated.

Q. Name some hormones which act through cyclicAMP as the second messenger. (Page 410)

A. Glucagon, ACTH, TSH, ADH, FSH, LH.

Q. Name some second messengers. (Page 412)A. Cyclic AMP, 1,2-diacyl glycerol, inositol

triphosphate, and calcium.

Q. Name some hormones which act through cyclicGMP as the second messenger. (Page 410)

A. ANF (atrial natriuretic factor).

Q. Name some hormones that bind to intracellularreceptors. (Page 413)

A. Glucocorticoids, mineralocorticoids, estrogens,progesterone, androgens, and thyroxin.

Hormones-I 243


Q. What are hypothalamic neuropeptides?(Page 414)

A. These neurohormones are antidiuretic hormone(ADH) and oxytocin.

Q. Name the important hypothalamic releasing factors.(Page 415)

A. TRH (thyrotropin releasing hormone), GnRH(gonadotropin releasing hormone), GHRH(growth hormone releasing hormone),somatostatin (growth hormone inhibitory factor),CRF (corticotropin releasing factor), and PIF(prolactin inhibitor factor).

Q. Alpha chain of human chorionic gonadotropin(HCG) is shared with what else? (Page 415)

A. TSH, FSH, LH and HCG have the common alphachain, and beta chains are specific.

Hormones-II:Pituitary Hormones


Q. What are the hormones produced by anteriorpituitary? (Page 415)

A. GH (Growth hormone), ACTH (Adrenocorti-cotropic hormone), LH (Luteinising hormone),FSH (Follicle stimulating hormone), TSH (Thyroidstimulating hormone), MSH (Melanocytestimulating hormone), and PRL (Prolactin).

Q. What is the major effect of growth hormone?(Page 415)

A. GH increases the uptake of amino acids by cells,enhances protein synthesis, and produces positivenitrogen balance. The anti-insulin effect of GHcauses lipolysis and hyperglycemia. The overalleffect of GH is to stimulate growth of soft tissues,cartilage and bone. It is anabolic.

Q. Increased secretion of growth hormone will leadto what condition?

A. Excess secretion of GH secretion leads togigantism in children and acromegaly in adults.

(Page 415)

Q. What is the result of decreased growth hormonesecretion? (Page 415)

A. Deficiency of GH secretion in early childhoodresults in pituitary dwarfism.

Q. What is the function of FSH? (Page 416)A. FSH stimulates growth of ovarian follicles in females

and spermatogenesis (Sertoli cells) in males.

Q. What is the function of LH? (Page 416)A. Testosterone in males (secreted by Leydig

interstitial cells) and progesterone in females(secreted by corpus luteum), are increased underthe influence of LH.

Hormones-II 245


Q. The 11-hydroxylase is required for the synthesisof which hormone?

A. Cortisol. (Page 417)

Q. The 17-hydroxylase is required for the synthesisof which hormones?

A. Cortisol, testosterone, and estradiol.(Page 417 and 418)

Q. Which is the precursor of steroid hormones?

A. Cholesterol. (Page 417)

Q. What are the hormones produced fromprogesterone? (Page 417)

A. Corticosterone, aldosterone, testosterone, andestrogens.

Q. Cortisol has how many carbon atoms?(Page 417)A. 21.

Q. Aldosterone has how many carbon atoms?(Page 418)

A. 21.

Hormones-III:Steroid Hormones


Q. Testerone has how many carbon atoms?(Page 418)

A. 19.

Q. Estrogen has how many carbon atoms?(Page 418)

A. 18.

Q. What is the immediate precursor of estrogens?(Page 418)

A. Testosterone.

Q. What are the structural features of estradiol?(Page 418)

A. Cyclopentanophenanthrene ring, total 18 carbonatoms, aromatic character of A ring, and hydroxylgroups on 3rd and 17 carbon atoms.

Q. 21-hydroxylase is required for the synthesis ofwhich hormone?

A. Aldosterone. (Page 418)

Q. What are the effects of glucocorticoids?(Page 419)

A. Increased gluconeogenesis, augmented lipolysis,elevated protein breakdown, and depressedimmune function

Hormones-III 246


Q. What is the precursor of thyroxin? (Page 423)A. Tyrosine.

Q. Name some antithyroid agents. (Page 423)A. Thiocyanate, perchlorate, and methimazole.

Q. How thyroid hormones are produced?(Page 423)A. Tyrosine residues of thyroglobulin are iodinated.

Q. What is the function of thyroid stimulatinghormone? (Page 423)

A. It increases the uptake of iodine by thyroid gland,enhances the oxidation of iodine to iodide, andfavours the hydrolysis of thyroglobulin toproduce T4.

Q. What is the ratio of T4 and T3 in blood?(Page 424)

A. Blood concentration of T4 is 70 times more thanof T3.

Hormones-IV:Thyroid Hormones


Q. What are the functions of thyroid hormones?(Page 424)

A. Calorigenic effect or thermogenesis and BMR isincreased.

Q. How this is produced? (Page 424)A. The thermogenic effect is mediated by uncoupling

of oxidative phosphorylation. Thyroxine in largequantities can swell the mitochondria. Basalmetabolic rate (BMR) is increased.

Q. What are the biochemical features of thyroidhormones? (Page 424)

A. Thyroxine increases cellular metabolism.Gluconeogenesis and carbohydrate oxidation areincreased. Glucose tolerance test shows rapidabsorption. Fatty acid metabolism is increased.

Q. Deficiency of thyroxine results in whichcondition? (Page 426)

A. Myxedema.

Q. What are the salient features of hypothyroidism?(Page 426)

A. Decreased T3 level, increased TSH level, lethargy,hypercholesterolemia, weight gain, and decreasedbasal metabolic rate.

Q. What are the characteristic features of primaryhyperthyroidism?

A. High TSH and T4 levels, increased rate ofmetabolism, weight loss, tachycardia, fine tremors,sweating, diarrhea, emotional disturbances, anxietyand sensitivity to heat. (Page 426)

Hormones-IV 249


Q. Why sodium fluoride is used as a preservativeof blood for glucose estimation? (Page 427)

A. To prevent glycolysis and to prevent loss of sugar.

Q. What are the preservatives used in urine sample?(Page 427)

A. Formalin, thymol, chloroform, toluene,concentrated HCl and glacial acetic acid are thecommonly used urine preservatives.

Q. What is optical density? (Page 428)A. Optical density = minus logT.

Q. What is Beer-Lambert�s law? (Page 428)A. As per Beer�s law, the intensity of the colour is

directly proportional to the concentration of thecoloured particles in the solution. The Lambert�slaw states that the amount of light absorbed by acoloured solution depends on the length of thecolumn or the depth of the liquid through whichlight passes.

Clinical Biochemistry-I


Q. What is end point analysis? (Page 428)A. Serum sample and reagents are mixed and

incubated for a fixed time, to develop the colouroptimally. Then, the OD is ascertained and theconcentration of the substances is calculated. Thisis called end point analysis.

Q. What is kinetic method? (Page 429)A. Serum and reagents are incubated, and readings

are taken at 2 and 3 minutes exactly, and from thedifference in OD between the two values, theconcentration is calculated. Here the optimumcolour is not developed, but is quicker and henceis often used in autoanalysers.

Q. What is accuracy? (Page 430)A. Accuracy is the closeness of a result to the true

value.

Q. What is meant by the term precision? (Page 430)A. Precision refers to the reproducibility of the result.

Precision depends on the technique, the reagents,as well as on the technician.

Q. What is meant by specificity? (Page 430)A. Specificity of a reaction denotes that only one

substance will answer that particular test.Specificity is determined by the method of theanalysis.

Clinical Biochemistry-I


Q. What is the normal serum bilirubin level?(Page 431)

A. 0.2 to 0.8 mg/dl.

Q. What is the normal blood level of unconjugatedbilirubin? (Page 431)

A. 0.2-0.6 mg/dl.

Q. What is the normal serum level of conjugatedbilirubin? (Page 431)

A. Less than 0.2 mg/dl.

Q. What is latent jaundice? (Page 431)A. Serum bilirubin between 1 mg/dl and 2 mg/dl.

Q. Jaundice appears at what level of bilirubin?(Page 431)

A. Jaundice appears if the serum bilirubin goes above2 mg/dl.

Clinical Biochemistry-II:Liver and Gastric Function Tests


Q. What is meant by van den Bergh�s direct positivetest? (Page 431)

A. When bilirubin is conjugated, the purple colouris produced immediately on mixing with thereagent, the response is said to be van den Bergh�sdirect positive.

Q. What is indirect positive van den Bergh�s test?(Page 431)

A. When the bilirubin is unconjugated, the colour isobtained only when alcohol is added, and thisresponse is known as indirect positive.

Q. What type of bilirubin is present in hemolyticjaundice? (Page 431)

A. In hemolytic jaundice, unconjugated bilirubin isincreased in serum. Hence van den Bergh�s test isindirect positive.

Q. What happens in obstructive jaundice?(Page 431)

A. In obstructive jaundice, conjugated bilirubin inserum is elevated, and van den Bergh�s test isdirect positive.

Q. What about hepatocellular jaundice? (Page 431)A. In hepatocellular jaundice, a biphasic reaction is

observed, because both conjugated and unconju-gated bilirubins are increased in serum.

Q. What are important liver function tests?(Page 432)

A. Serum bilirubin, albumin, alkaline phosphatase,urine bile salts, bile pigments and urobilinogen.

Clinical Biochemistry-II


Q. Increase in serum unconjugated bilirubin occursin which condition?

A. Hemolytic jaundice. (Page 433)

Q. What are the features of obstructive jaundice?(Page 433)

A. Elevated conjugated bilirubin in plasma, presenceof bile salts and bile pigments in urine, increasedalkaline phosphatase level in blood, and increasedcholesterol in blood.

Q. Which tests will be positive in a urine of a patientwith obstructive jaundice? (Page 433)

A. Gmelin�s test, Hay�s test, and Fouchet�s test.

Q. What are the enzymes useful in diagnosis of liverdiseases? (Page 433)

A. Alanine amino transferase, alkaline phosphatase,and gamma glutamyl transferase.

Q. What are the salient laboratory findings in apatient with chronic liver disease? (Page 433)

A. Serum albumin is lowered, albumin globulin ratiois reversed, and prothrombin time is prolonged.

Q. What is the characteristic laboratory findings inalcoholic cirrhosis?

A. Elevation of gamma glutamyl transferase level inserum. (Page 433)

Q. What are the important stimulants for gastric acidsecretion?

A. Gastrin, vagus stimulation, and histamine.(Page 434)


Q. What is alkaline tide? (Page 434)A. When HCl is produced in stomach, bicarbonate

level within the cell increases (formed fromH2CO3), it is reabsorbed into blood stream. Thiswould account for the alkaline tide of plasma andurine, immediately after meals.

Q. What is the maximal gastric acid output?(Page 435)

A. It is the acid output in millimol per hour, afterthe stimulation.

Q. What is the upper limit of maximal gastric acidoutput? (Page 435)

A. 30 mmol/ hour in females and 45 mmol/hour inmales.

Q. What is basal acid output? (Page 435)A. It is the acid output in millimol per hour, in the

absence of all intentional stimulation.

Q. What is the upper limit of basic acid output?(Page 435)

A. 5 millimol/hour in females and 10 millimol inmales.

Q. Hypo-acidity is found in which conditions?(Page 435)

A. Pernicious anemia, carcinoma of stomach, andatrophic gastritis.

Clinical Biochemistry-II


Q. How much is glomerular filtration rate?(Page 436)

A. 120-125 ml per minute.

Q. What is the function of glomerulus? (Page 436)A. An ultrafiltrate of the blood is produced in

glomerulus, while the cells and proteins areretained in the blood.

Q. What is the normal renal threshold value forglucose? (Page 437)

A. Blood level of 180 mg/ dl.

Q. What is the normal specific gravity of urine?(Page 438)

A. 1.015 to 1.025.

Q. What is the minimum and maximum specificgravity of urine?

A. 1.003 to 1.032. (Page 438)

ClinicalBiochemistry-III:Kidney Function Tests


Q. What is the specific gravity of urine in chronicrenal failure?

A. Fixed to 1.010. (Page 439)

Q. Specific gravity of urine increased in whichcondition? (Page 439)

A. Acute glomerulonephritis.

Q. Polyuria is seen in which conditions?(Page 439)A. Diabetes mellitus, diabetes insipidus, and chronic

renal failure.

Q. What are the features of chronic renal failure?(Page 439)

A. Urine with fixed specific gravity of 1.010, polyuria,increased blood urea and creatinine.

Q. Name abnormal substances seen in urine.(Page 439)

A. Protein, blood, sugar, ketone bodies, bile salts,bile pigments, and urobilinogen.

Q. Proteinuria is seen in which conditions?(Page 439)

A. Acute glomerulo nephritis, nephrotic syndrome,pyelonephritis, and multiple myeloma

Q. Which test is commonly employed to detecturinary protein?

A. Heat and acetic acid test. (Page 439)

Q. What is micro-albuminuria? (Page 439)A. When small quantities of albumin (50-300 mg/

day) is seen in urine.


Q. How proteinurias are classified? (Page 439)A. Glomerular proteinuria, overflow proteinuria,

nephron loss proteinuria, tubular proteinuria, andurogenic proteinuria.

Q. What is meant by renal clearance? (Page 441)A. Clearance is defined as the quantity of blood or

plasma completely cleared of a substance per unittime and is expressed as milliliter per minute. Itis the ml of plasma which contains the amount ofthat substance excreted by the kidney within aminute.

Q. How renal plasma flow is measured? (Page 441)A. Para amino hippurate (Diodrast) clearance.

Q. What is the correct method for assessingglomerular filtration rate?

A. Inulin clearance. (Page 441)

Q. What is its disadvantage? (Page 441)A. Inulin has to be infused intravenously throughout

the test period.

Q. What is the normal value for PAH clearance ?(Page 442)

A. About 700 ml/min.

Q. What is the best method for assessing glomerularfiltration rate?

A. Creatinine clearance test. (Page 442)

Q. What is the advantage of creatinine test?(Page 442)

A. Creatinine is formed spontaneously (non-enzymatic), so the blood level and excretion rateof creatinine is a constant from day to day.


Q. What is the normal value of creatinine clearance?(Page 442)

A. In males 85-125 ml/min and in females 80-115 ml/min.

Q. What is the significance of creatinine clearance?(Page 442)

A. A decreased creatinine clearance is a verysensitive indicator of a reduced glomerularfiltration rate.

Q. What is the normal creatinine level in blood?(Page 442)

A. For adult males, 0.7-1.4 mg/dl, for adult females,0.6-1.3 mg/dl.

Q. What is creatinine coefficient? (Page 442)A. It is the urinary creatinine expressed in mg/kg

body weight.

Q. What is the significance of creatinine coefficient?(Page 442)

A. The value is elevated in muscular dystrophy.

Q. What is the normal value of creatinine coefficient?(Page 442)

A. Normal range is 20-28 mg/kg for males and 15-21 mg/kg for females.

Q. Urea clearance is lowered in which condition?(Page 443)

A. Chronic liver failure.

Q. What is the maximum urea clearance value?(Page 443)

A. 75 ml/minute.


Q. What is the standard urea clearance value?(Page 443)

A. 54 ml/minute.

Q. When do you call it standard urea clearance?(Page 443)

A. When the volume of urine formed is less than 2ml per minute.

Q. What is the normal blood urea level? (Page 443)A. 20-40 mg /dl.

Q. What is the clinical significance of increased urealevel in blood ?

A. Urea level is increased in renal failure.(Page 443)

Q. How failure of concentrating capacity of urine ismeasured ?

A. Concentration test (Water deprivation test).(Page 444)

Q. How is tubular concentrating capacity measured?(Page 444)

A. Urine specific gravity.

Q. What are the usual tests to assess tubularfunction? (Page 444)

A. Measurement of specific gravity, concentrationtest, dilution test, acidification test.

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Biochemistry Viva Questions