1

BIOCHEM 1a

LECTURE 1: PROTEINS (AMINO ACIDS)

PROTEINS: AMINO ACIDS

I. TWO TYPES OF PROTEINS II. FUNCTIONS OF PROTEINS

III. AMINO ACIDS

IV. EFFECT OF pH ON PROTEINS V. PEPTIDE BOND FORMATION

VI. DEFINITION OF TERMS

ORDER OF PROTEIN STRUCTURES

I. PRIMARY STRUCTURE

II. SECONDARY STRUCTURE III. TERTIARY STRUCTURES

IV. QUARTERNARY STRUCTURES

OTHER CONCEPTS IN PROTEINS I. DETERMINATION OF PRIMARY STRUCTURES OF PROTEINS

II. PROTEIN FOLDING II. STUDYING THE TERTIARY STRUCTURES OF PROTEINS

IV. DISEASES RELATED TO PROTEIN FOLDING

V. EXAMPLES OF PROTEINS

LECTURE 2: CARBOHYDRATES

CARBOHYDRATES

I. FUNCTIONS OF CARBOHYDRATES II. REQUIREMENTS TO BE CONSIDERED A CARBOHYDRATE

II. DISEASES INVOLVED IN CHO METABOLISM

SOME IMPORTANT CARBOHYDRATES I. MONOSACCHARIDES

II. DISACCHARIDES III. POLYSACCHARIDES

CHARACTERISTICS OF CHO

I. STRUCTURES OF CARBOHYDRATES II. CARBOHYDRATE DERIVATIVES

III. SUGARS HAVE REDUCING PROPERTIES

IV. CARBOHYDRATES IN THE CELL MEMBRANE

LECTURE 3: LIPIDS

LIPIDS

I. FUNCTIONS OF LIPIDS: II. FATTY ACIDS

III. TRIACYLGLYCEROLS (TRIGLYCERIDES)

LIPID CLASSIFICATION I. PHOSPHOLIPIDS

II. GLYCOLIPIDS III. CHOLESTEROL

LECTURE 4: BIOENERGETICS

BIOENERGETICS

I. LAWS OF THERMODYNAMICS II. METABOLISM

III. FREE ENERGY (G) IV. STEPS IN HARNESSING ENERGY FROM FOOD

V. SYNTHESIS OF ATP

2

LECTURE 1: PROTEINS (AMINO ACIDS)

PROTEINS: AMINO ACIDS -most important in terms of function of cell

-polypeptide that has attained a unique stalk 3-D Shape (Conformation) which is functional (Native)

-amino acid sequence and shape determines function

-sequence is based on information coming from the gene

I. TWO TYPES OF PROTEINS

A. Simple Proteins

-contain only Amino Acids and no other Chemical Groups

-ex) Ribonuclease, Chymotrypsin

B. Complex Proteins

-has some other chemical component (Prosthetic Group)

-ex) Lipoproteins -Lipids -ex) Lipoprotein

Glycoproteins -Carbohydrates -ex) Globulin of Blood

Phosphoproteins -Phosphate -ex) Casein of Milk

Hemoproteins -Heme -ex) Hemoglobin

Metalloproteins -Iron, Zinc -ex) Ferritin,

II. FUNCTIONS OF PROTEINS

Catalytic Role: Enzymes

Antibodies of Immune System: Immunoglobulins, Interferon

Transporters to more materials around: Hemoglobin, Albumin, Lipoprotein

Regulators: Hormones, Insulin, Calmodulin

Structural Roles: Collagen, Elastin, Keratin

Agents of Motion: Cilia, Flagella, Muscles

Contraction: Actin, Myosin

Receptors: Glycophorin, LDL Receptor

Gene Regulation: Histones, Repressor Proteins

Nutrient and Storage Role: Casein (Milk)

III. AMINO ACIDS (Monomers of Proteins)

A. Structure Components of Amino Acids:

o Amino Group

o Carboxyl Group

o Chiral Carbon

o R-Group

B. Configuration Vs. Conformation

**Conformation -3-D arrangement / architecture of the protein

**Configuration -Geometric arrangement between a given set of atoms

-ex) D-Alanine, L- Alanine

L-Sterioisomer: predominant in nature, beneficial to life

D-Sterioisomer: toxic to life

Dextrotatory AA

Levorotatory AA: present in mammals as free AA and is not incorporated in proteins

C. Classifications of Amino Acids

1. Non-Polar Amino Acids -Hydrophobic Interactions, Vander Walls

2. Polar Uncharged -H-Bonding

3. Polar Charged -Electrostatic Interactions

3

NON POLAR AMINO ACIDS (net charge = 0 at pH=7.4; pI=6)

AMINO ACID DESCRIPTION 3-LETTER SYMBOL ONE LETTER SYMBOL

GLYCINE Aliphatic, No Chiral Center GLY G

ALANINE Aliphatic ALA A

VALINE Aliphatic VAL V

LEUCINE Aliphatic LEU L

ISOLEUCINE Aliphatic ILE I

PHENYLALANINE Aromatic PHE F

TRYPTOPHAN Aromatic, Indole Group TRP W

METHIONINE Thioether Group, w/ Sulfur MET M

PROLINE Imino Acid PRO P

POLAR UNCHARGED AMINO ACIDS (net charge = 0 at pH=7.4; pI=6)

SERINE Alcohol SER S

THREONINE Alcohol THR T

CYSTEINE Thiol Group CYS C

ASPARAGINE Amide ASN N

GLUTAMIN Amide GLN Q

TYROSINE Aromatic, Alcohol TYR Y

ACIDIC AMINO ACIDS (POLAR CHARGED) (net charge = -1 at pH=7.4; pI=3)

ASPARTATE Carboxylate ASP D

GLUTAMATE Gamma-Carboxylate GLU E

BASIC AMINO ACIDS (POLAR CHARGED) (net charge =+1 at pH=7.4; pI=10)

LYSINE Epsilon-Amino Group LYS K

ARGININE Guanido Group ARG R

HISTIDINE Aromatic, Imidazole Group HIS H

**Special Amino Acids

L-Ornithine -Urea Synthesis

L-Citrulline -Urea Synthesis

L-Argininosuccinate -Urea Synthesis

L-Tyrosine -Thyroid Hormone

L-Glutamate -Neurotransmitter

4-Hydroxyproline -Collagen

Hydroxylysine -Collagen

Carboxyglutamic Acid -Thrombin, Fibrin

D-Aspartate -Brain Tissues

D-Serine -Brain Tissues

D-Alanine -Bacterial Cell Walls

D-Glutamate -Bacterial Cell Walls

4

IV. EFFECT OF pH ON PROTEINS

-changing pH will alter the charge of a protein -this alters solubility and may change the shape of the protein (may cause denaturation)

Decrease pH : Net Charge = (+)

pH 7 : Net Charge = 0

Increase pH : Net Charge = (-) A. Titration of Amino Acids pK1 -Ionization of Proton attached to Carboxyl Group

PK2 -Ionization of Proton attached to NH3+

pK3 -Ionization of Proton attached to R-groups

**Polar Environment -favors R-COO- and R-NH3+

**Non-Polar Environ. -favors RCOOH and RNH2

B. Zwitterion Molecule -Net Charge of Region = 0

-not migrate toward either cathode or anode **pI = Isoelectric Point -point where Amino Acid has a Net Charge = 0 (important for diagnosis)

C. Amino Acids as a Buffer -Buffer Region is equal to +1, -1 of a pK value (at the point where there is 50:50 Ratio)

-at pK values, 50% of Amino Acid Ionized, and 50% has not, therefore, 50% is a Proton Donor, and 50% is a Proton Acceptor; this region is a good Buffer

**Amphoteric -capable of donating a Proton (Acid) and accepting a Proton (Base) **Buffer -resists drastic change in pH

V. PEPTIDE BOND FORMATION -Carboxyl Group of Previous A.A. forms a covalent bond with Amino Group of next A.A

-formed during protein synthesis

-interactions will now be done by the R-Groups because Nt and Ct are involved in Peptide Bonds

-amino acids in polypeptides are called Aminoacyl Residues

-peptide bonds are uncharged at any pH

A. Characteristics of Peptide Bonds (Trans-Peptide Bonds)

Peptide Bonds have partial Double Bond Characters (Cannot rotate)

Psi Bonds (between Alpha-Carbon and Carboxyl Atom) can rotate

Phi Bonds (between Amino Group and Alpha-Carbon) can rotate

B. Peptides with Physiologic Activity

1. Glutathione (Sigma – Glutamyl – Cysteinyl – Glycine)

2. Alanyl – Glutamyl – Glycyl – Lysine

VI. DEFINITION OF TERMS

Monomeric -spontaneous folding only in one peptide (Tertiary Structure)

Multimeric -folding of two or more polypeptides with non-folding patterns

-ex) Tetrameric: Hemoglobin (Quarternary Structure)

Homomeric -if both sub-units are identical

5

Heteromeric -if two or more types of chains are present in one protein

-ex) Hemoglobin (2-Alpha; 2-Beta)

ORDER OF PROTEIN STRUCTURES BASIS BOND TYPES

PRIMARY Amino Acid Sequence Covalent Peptide Bonds

Disulfide Bonds

SECONDARY Folding into A-Helix or B-Sheet H-Bonds (local interactions)

TERTIARY 3-D Folding of single polypeptide H-Bonds

Electrostatic Reactions

Hydrophobic Effect

Vander Waals

QUARTERNARY Association of 2 or more folded polypeptides to form a

multimeric protein

H-Bonds

Electrostatic Reactions

Hydrophobic Effect

Vander Waals

I. PRIMARY STRUCTURE

-sequence of amino acids Amino acid residues

-Nt –AAAAAAAA- Ct

-made up of Covalent Peptide Bonds and Disulfide Bonds

- determines function and fate

II. SECONDARY STRUCTURE

-comes as a complex structure resulting from interactions of Amino Acid residues

-consider the types of Amino Acids (polar or non polar)

-depends on the charges in Amino Acids

-Supersecondary Structures -secondary / tertiary

A. Alpha Helix

-Ampiphatic Right Hand Helices (R-groups face outward)

-Intramolecular H-Bonding (within molecule) and Vander Waals

-C=O of nth interact with N-H of n+4

-Pitch = 5.4 or 0.54nm

-every turn has 3.6 Residues of Amino Acids (36 per 10 turns) Promote A-Helix Destabilize A-Helix Terminate A-Helix

Ala A

Asn N

Cys C

Gln Q

His H

Leu L

Met M Phe F

Trp W

Tyr Y

Val V

Arg R

Glu E

Asp D

Gly G

Lys K

Ile I

Ser S Thr T

Pro P

Hyp….

**Keratin (in Hair) -spring like because of Keratin Protein (to straighten hair, we wet it)

-hair does not dissolve in water because Alpha-HeliX is Ampiphatic

-because of Hydrophobic Amino Acids which go away from water

-in rebonding, they add a reducing agent to break disulfide bonds, then they add

an oxidizing agent to arrange disulfide bonds

**Ramachadran Plot -map w/c describes backbone conformation of any polypeptide

-Beta (upper left); Alpha (middle)

6

**Ramachandran Angles -angles phy and psi

B. Beta Sheet

-Stabilized by Intermolecular H-Bonding between polypeptide chains

-2 residue repeat distance = 7.0A or 0.70nm

-usually found in long proteins

-requires 2-strands to form B-Sheet

-can be Intermolecular (2 strands) of Intramolecular (w/in 1 strand)

-Glycine can squeeze into bends

-two types: Parallel (NC and NC) and Anti-Parallel (NC and CN)

-ex) Silk - stretching silk will break it because it is already in its fully extended form (Beta-sheet)

1. Domain

-two or more distinct modules

2. Motifs

-recurring substructures

-includes the B-A-B Motif + Hairpin Loop Motif

-B-A-B Motif: beta sheet Alpha Helix beta sheet (contains a parallel beta sheet)

-Hairpin Loop Motif: 2 beta sheets not facing the same direction (anti parallel)

C. Other Secondary Structures

1. Bends

-joining of two secondary structures (short)

2. Loops/Turns

-forms Supersecondary Structures

-has an irregular conformation

-gives flexibility to the protein

-found in Helix – Loop – Helix Motifs (DNA) and Epitopes (Antibodies)

Motifs - repeat structure which occurs regularly at intervals

Epitopes - loops on surface which are readily accessible sites

3. Random Coil -irregular structures

III. TERTIARY STRUCTURES

-3-D Arrangement of proteins which is a combination of several secondary structures

-may be Globular / Fibrous

-Surface of protein contains polar amino acids; Interior of protein contains non-polar amino acids

-stabilized by non-covalent interactions (Hydrophobic Interactions, Electrostatic / Ionic Bonding, Van der Waal’s

or Hydrogen Bonding)

-includes Domains (Supersecondary Structures) to perform a particular function

B-A-B Motif: beta sheet Alpha Helix beta sheet (contains a parallel beta sheet)

B-Hairpin Motif: 2 beta sheets which are anti parallel

A-A Motif

B- Barrels

IV. QUARTERNARY STRUCTURES

-requires more than one polypeptide

-stabilized by non-covalent interactions: Hydrophobic Interactions, Electrostatic / Ionic Bonding, Van der

Waal’s, Hydrogen Bonding)

7

OTHER CONCEPTS IN PROTEINS

I. DETERMINATION OF PRIMARY STRUCTURES OF PROTEINS

-before a protein is studied, it should be in its simplest form -we must first determine a protein’s primary structure

A. Electrophoesis -separated according to charge (anode vs. cathode)

-clear bonds signify successful purification -separation of charged molecules based on rates of migration

B. Gel Filtration -small molecules come out last

-separation based on Stoked Radius (diameter of sphere as they tumble in solution)

C. Other Methods

Column Chromatography

Partition Chromatography

Absorption Chromatography

Ion Exchange Chromatography

Hydrophobic Interaction Chromatography

Affinity Chromatography

II. PROTEIN FOLDING -polypeptides are helped by Chaperones for correct folding of protein -when proteins are being synthesized, they are already being helped

-folding of proteins is spontaneous, but sometimes, wrong folding occurs -system in cells where other proteins help proteins fold (chaperone)

-Aggregates are proteins which have failed to refold spontaneously **Chaperones -necessary for proper tridimentional structure of protein

-maintains the proteins in unfolded state while protein synthesis takes place -inhibits unnecessary protein-protein interactions

Enclosed Forming Protein Chaperones Help in Folding Protein is Released

**Denaturation of Proteins -unfolding of proteins **Aggregates -proteins which have failed to refold spontaneously

III. STUDYING THE TERTIARY STRUCTURES OF PROTEINS -to study the tertiary structure, we must get protein at its native structure

A. X-Ray Crystallography

-used to measure DNA structure -proteins are crystallized then X-rayed -precipitation of a protein under condition in which it forms crystals that defract X-rays

-with a film, tertiary structure can be studied (no computers!) B. Nuclear Magnetic Resonance Spectroscopy

-measures the absorbance of radio frequency electromagnetic energy

8

C. Molecular Modeling

IV. DISEASES RELATED TO PROTEIN FOLDING

A. Alzheimer’s Disease

-B-Amyloid Proteins change into plaques

-40 residue segment cleaved from precursor protein

-change from Alpha Helix to Beta Sheet (because of 4 genes)

-destroys the Hypoccampus

B. Madcow’s Disease

-Alpha Helices are transformed into Beta Sheets

-Prions are infected (infectious protein w/o nucleic acid)

PrP (Prion Relative Proteins) -Alpha Helix

PrPSc (Pathologic) TSE -should not reach the brain

-Hydrophobic R-Groups are exposed (insoluble)

-Beta Sheet

V. EXAMPLES OF PROTEINS

A. Alpha Keratin

-found in Hair, Wool, Feathers, Nails, Claws, Scale, Horns, Hooves, etc

-Right handed Alpha-Helix

-Rich in F, I, V, M, A

-cross links contributed by Disulfide bonds (cysteine)

B. Collagen

-fibrous protein found in Connective Tissues, Tendons, Cartilage, Cornea (most abundant)

-functional collagen is a triple helix (right handed)

-Left handed twist is formed by the triple helix

-Unique collagen helix with unusual angles

-Helix is stabilized by Steric Repulsions

-3.3 Amino acids per turn

-Glycine is present in every third residue

-Hydoxylysine involved in H-bonds

-constant composition: G, A, P, Hydroxyproline

-damaged in diabetic people (high glucose level)

-fragile collagen may result to scurvy: bleeding gums, skin discoloration (caused by

Vitamin C deficiency)

9

LECTURE 2: CARBOHYDRATES

CARBOHYDRATES -Carbohydrates may be attached to proteins or to lipids in the membrane

I. FUNCTIONS OF CARBOHYDRATES

Energy: Glucose is the main fuel of the cell

Storage: Starch (plants) and Glycogen (animals)

Structural: Cellulose / Chitin; Hemicellulose; Agar; Spectin

Cell to Cell Signalling

Antigen / Markers

Fillers for Drugs

Proteoglycans / Mucopolysaccharides

Cell Membrane Component (Glycolipid, Glycoroteins)

Antibiotics

II. REQUIREMENTS TO BE CONSIDERED A CARBOHYDRATE

A. Must have a Carbonyl Group ( --C=O)

o Ketone (Ketose)

o Aldehyde (Aldose)

**AnUmeric Carbon -Carbon which contains the functional group

-for Aldoses, Anumeric Carbon in C-1

-for Ketoses, Anumeric Carbon in C-2

-functional groups have Reducing Property

B. Must have more than one Hydroxyl Group (-OH)

C. Number of Carbon atoms gives the classifications:

o TrioseS

o Tetroses

o Pentoses (important in nucleotides and coenzymes)

o Hexoses (most common)

III. DISEASES INVOLVED IN CHO METABOLISM

Diabetes Mellitus

Galactosemia

Glycogen Storage Diseases

Lactose Intolerance

10

SOME IMPORTANT CARBOHYDRATES

I. MONOSACCHARIDES

-carbohydrates that cannot be hydrolyzed into simpler carbohydrates

-may be classified as Trioses, Tetroses, Pentoses, Hexoses, Heptoses

-may also be classified as Aldoses or Ketoses depending on the functional group present

SUGAR WHERE FOUND BIOCHEMICAL IMPORTANCE

HEXOSES

D-Glucose Fruit Juices, Cane Sugar

Hydrolysis of Starch

Lactose, Maltose

Sugar of the body carried by blood and used by tissues

D-Fructose Fruit Juices, Honey

Hydrolysis of Cane Sugar

Hydrolysis of Inulin

Can be changed to glucose in the liver to be used by body

D-Galactose Hydrolysis of Lactose Can be changed to glucose in liver and metabolized.

Used to make lactose in milk (mammary glands).

Constituent of glycolipids & glycoproteins

D-Mannose Hydrolysis of Plant Mannans Constituent of many Glycoproteins

PENTOSES

D-Ribose Nucleic Acids

Structural elements of nucleic acids and coenzymes (ATP,

NAD, NADP)---

Ribose Phosphate is an intermediate to pentose phosphate

pathway

D-Ribulose Formed in metabolic processes Ribulose Phosphate is an intermediate in pentose phosphate

pathway

D-Arabinose Gum Arabic (Plum) Constituent of Glycoproteins

D-Xylose Wood gums, Proteoglycans

Glycosaminoglycans

Constituent of Glycoproteins

D-Lyxose Heart Muscle

Constituent of a lyxoflavin isolated from human heart muscle

D-Xylulose Intermediate in Uronic Acid

Pathway

**Glucose -most important carbohydrate

-most dietary carbohydrates are converted into glucose in the liver

-precursor for synthesis of all other carbohydrates in the body

**L-Gulonate -intermediate in the Uronic Acid Pathway

**D-Glucoronate -for Glucuronide formation and in Glycosaminoglycans

**L-Iduronate -metabolic derivative of D-Glucoronate

**Ouabain -inhibitor of Na+K+ATpase of cell membranes

**Streptomycin -antibiotics

**Glucoside -Glucose + OH group (form of Glycoside)

**Galactoside -Galactose + OH group (form of Glycoside)

**Deoxyribose -found in DNA

**Deoxysugar L-Fucose -occurs in Glycoproteins

**2-Deoxyglucose -used as an inhibitor of glucose metabolism

11

**D-Glucosamine -constituent of Hyaluronic Acid

**D-Galactosamine -Chondrosamine: a constituent of Chondroitin

II. DISACCHARIDES

-condensation products of two monosaccharide units

-important disaccharides include Maltose, Sucrose, Lactose

-Oligosaccharides: condensation of 2-10 monosaccharides -ex) Maltotriose

**Glycosidic Bonds -covalent bond which connects two sugars together

SUGAR SOURCE CLINICAL SIGNIFICANCE

Maltose

Glucose + Glucose

Digestion by amylase or hydrolysis of

starch

Lactose

Galactose + Glucose

Milk (may occur in urine during

pregnancy)

In lactase deficiency, malabsorption leads to

diarrhea and flatulence

Sucrose

Glucose + Fructose

Cane and beet sugar

Sorghum, Pineapple, Carrot Roots

In sucrase deficiency, malabsorption leads

to diarrhea and flatulence

Trehalose Fungi and Yeasrs

Major Sugar of Insect Hemolymph

**Maltose -A(14) Glycosidic-linkages with Glucose monomer units

**Isomaltose -A(16) Glycosidic-linkages with Glucose monomer units

**Lactose -B(14) Glycosidic linkages with Glucose and Galactose

**Sucrose -A(14) Glycosidic linkages with Glucose + Fructose

-not a reducing sugar because it has no free functional group

12

III. POLYSACCHARIDES -condensation of more than ten monosaccharide units which may be linear or branched polymers

-may be classified as Hexosans or Pentosans

-for storage and structural functions

A. Homopolysaccharides (same monomer units)

1. Starches -homopolymer of glucose forming A-Glucosidic Chains

-Glucosan or Glucan (A-Glucosidic Chains)

-most abundant dietary carbohydrate in cereal, potatoes, legumes

a. Amylose -non-branching helical structure

-can be digested because of A(14) Amylase

b. Amylopectin -consists of branched chains

-united by A(14) linkages in the chains

-united by A(16) linkages in the branches

2. Glycogen -storage polysaccharide in animals found in muscles and liver

-more highly branched than Amylopectin

-more important in the liver to deliver glucose to other tissues

-excess glucose is stored as glycogen in the liver

-A(14) and A(16) Glucosidic Linkages

3. Dextrins -intermediates in the hydrolysis of starch

4. Inulin -polysaccharide of Fructose (Fructosan)

-found in Tubers and Roots of Dahlias, Artichokes, Dandelions

-soluble in water

5. Cellulose -chief constituent of the framework of plants (Soluble)

-B-D-Glucopyranose units linked in B(14) bonds

-long straight chains strengthened by H-bonds

-cannot be digested by mammals because we lack enzymes to hydrolyze B-linkages

6. Chitin -structural polysaccharides in exoskeleton of crustaceans

-N-Acetyl-D-Glucosamine with B(14) Glycosidic Linkages

B. Heteropolysaccharides (different monomer units)

-contains sugars, sugar amines (amino sugars), sugar acids

1. Glycosaminoglycans -also known as Mucopolysaccharides

-complex carbohydrates characterized by content of amino sugars & uronic acids

**Proteoglycan -formed when chains are attached to a protein molecule

-provide ground or packing substance of connective tissues

-ex) Hyaluronic Acid, Chondroitin Sulfate, Heparin

2. Glycoproteins -also known as Mucoproteins

-occur in many different situations in fluids and tissues (cell membrane)

-proteins with branched or unbranched oligosaccharide chains

**Sialic Acids -N or O-acyl derivatives of Neuraminic Acid

-constituents of both Glycoproteins & Gangliosides

13

**Neuraminic Acid -9-Carbon sugar derived from Mannosamine & Pyruvate

CHARACTERISTICS OF CHO

I. STRUCTURES OF CARBOHYDRATES

A. Three Types of Representations Used:

1. Fischer Projection -two dimensional perspective

2. Haworth Projection -cyclic sugars

-may be a Pyranose (6 membered) or Furanose (5 membered)

-Amylene Bridge connects the Functional Group and Alcohol

**Hemiacetal -if the ring structure is formed by an Aldehyde and an Alcohol

**Hemiketal -if formed by a Ketone and an Alcohol Group

3. Chair Configuration -equitorial vs. axial positions

-Axial: parallel to the imaginary vertical axis

-Equatorial: perpendicular to the imaginary vertical axis

B. Isomerism in Sugars

-Number of Isomers = 2n; where n= # of chiral centers

-ex) in D-Glucose, there are 4 chiral centers, which means, D-glucose has 16 sterioisomers

** (1) Enantiomer: mirror image

** (14) Diasterioisomers: not sterioisomers nor mirror image

1. Enantiomer: Mirror Image

-either D or L form OR may also be (+) or (-)

-D/L and +/- are independent of each other

-most of the carbohydrates in mammals are D-Sugars

-depends on the Penultimate Carbon (last chiral center / 2nd

to the last Carbon)

**D-Sugar -if the Penultimate Carbon’s –OH is on the RIGHT

**L-Sugar -if the Penultimate Carbon’s –OH is on the LEFT

**Dextrorotatory (+) -rotated to the right

**Levorotatory ( - ) -rotated to the left

2. Anomers: Alpha and Beta

-depends on the Anomeric Carbon

-sugars where the –OH groups of the Anomeric Carbon differ in position

**Alpha -if –OH in Anomeric Carbon is in SAME side of Amylene Bridge

-OH is on the RIGHT side

**Beta -if –OH in Anomeric Carbon is OPPOSITE of Amylene Bridge

-OH is on the LEFT side

3. Epimers

-sugars that differ on orientation of –OH in only one carbon (except anomeric carbon)

-ex) Mannose and Glucose (C-2 Epimers)

Glucose and Galactose (C-4 Epimers)

4. Aldose-Ketose Isomerism

-ex) Fructose has same molecular formula as glucose but differs in its structural formula, since there is a

potential keto-group in Fructose and a potential aldehyde group in Glucose

14

II. CARBOHYDRATE DERIVATIVES

-Sugar Alcohol: product of reduction

-Sugar Acids: process of oxidation

A. Carboxylic Derivatives

1. Aldaric Acid -Ald-aric Acid / Ald-anate

-C-1 (functional) and C-6 (alcohol) are both oxidized

2. Aldonic Acid -Ald-onic Acid / Ald-onate

-C-1 only is oxidized

3. Uronic Acid -Ald-ronic Acid / Aldo-ronate

-C-6 only is oxidized

**Some Significant Sugar Derivatives:

L-Gulonate -intermediate in the Uronic Acid Pathway (Aldonic Acid)

D-Glucoronate -for Glucuronide formation and in Glycosaminoglycans

L-Iduronate -metabolic derivative of D-Glucoronate

B. Glycosides

-widely distributed in nature

-some examples that are important to medicine because of their action on the heart (Cardiac Glycosides)

all contain steroids as the Aglycone

-ex) Ouabain (inhibitor of cell membranes); Streptomycin (antibiotics)

-formed by condensation between the hydroxyl group of anomeric carbon and a second compound that

may or may not be another monosaccharide (may have an -OH group to form acetal links, or amine

group to form N-Glycosidic Bonds)

**Acetal Link -formed in Hemiacetal Group + -OH group

-Glucoside = Glucose + OH group

-Galactoside = Galactose + OH group

**N-Glycosidic Bond -formed in Hemiacetal Group + Amine Group

-ex) between Ribose ( hemiacetal) + Adenine (amino group)

C. Deoxysugars

-hydroxy group has been replaced by a hydrogen

-ex) Deoxyribose in DNA

Deoxy Sugar L-Fucose occurs in Glycoproteins

2-Deoxyglucose used as an inhibitor of glucose metabolism

D. Amino Sugars

-Amino groups replaces an –OH group

-ex) D-Glucosamine -constituent of Hyaluronic Acid

D-Galactosamine (Chondrosamine) -a constituent of Chondroitin

D-Mannosamine

Antibiotics

15

III. SUGARS HAVE REDUCING PROPERTIES

-to have reducing properties, a sugar must have a free Carbonyl group

-in Sucrose, Carbonyl Groups are not free anymore because of the linkages

**Reducing End

**Non Reducing End

IV. CARBOHYDRATES IN THE CELL MEMBRANE

-5% in Cell Membrane is Carbohydrate in Glycoproteins and Glycolipids

-Carbohydrates are also preset in apo B of Lipoproteins

-amino acids can bind with Sugar

1. Serine (OH): forms ether linkages (O-linkages)

2. Threonine (OH)

3. Asparagine (NH2)

-carbohydrates can also be found in extracellular matrix (Collagen, Glycosaminoglycans)

**Glycocalyx -carbohydrates on cell membrane

**Glycophorin -integral membrane glycoprotein of human erythrocytes and spans lipid membrane

16

LECTURE 3: LIPIDS

LIPIDS

-diverse structures

-includes fats, oils, steroids, waxes, and related compounds

-two common properties of all Lipids:

1. Insoluble in water

2. Soluble in non-polar solvents (such as ether and chloroform)

-stored in adipose tissue

I. FUNCTIONS OF LIPIDS:

High energy value

Fat soluble vitamins and essential fatty acids

Serves as thermal insulator in adipose tissue in the subcutaneous insulators

Act as electrical insulators, allowing depolarization waves (along myelinated nerves)

Important constituent in membrane and mitochondria (lipoproteins)

Transporting lipid in the blood

Protective padding and insulation of vital organs

II. FATTY ACIDS

-aliphatic carboxylic acids; building blocks

-occur mainly as esters in natural fats and oils but occur in the unesterified form as free fatty acids

-free fatty acids is a transport form found in the Plasma

-usually straight-chain derivatives containing an EVEN number of carbon atoms

-ampiphatic (with hydrophilic and hydrophobic ends)

**Nomenclature of Fatty Acids

1. Saturated Acids -end with –anoic

-ex) Octanoic Acid

2. Unsaturated Acids -end with –enoic

-causes the kinking (cis)

-ex) Oleic Acid

**Cis -same side (more common in nature)

**Trans -opposite sides

17

A. Saturated Fatty Acids

-containing no double bonds

-higher melting point

COMMON NAME # C DESCRIPTION

Acetic Acid 2 End product of carbohydrate fermentation by rumen

microorganisms

Propionic Acid 3 End product of carbohydrate fermentation by rumen organisms

Butyric Acid 4 In certain fats in small amounts (butter). End product of

carbohydrate fermentation by rumen organisms Valeric Acid 5

Caproic Acid 6

Lauric Acid 12 Spermaceti, Cinnamon, Palm Kernel, Coconut Oils, Butter,

Laurels

Myristic Acid 14 Nutmeg, Palm Kernel, Coconut Oils, Butter

Palmitic Acid 16 Common in all animal and plant fats

Stearic Acid 18

Arachidic Acid 20

Behenic Acid 22

Lignoceric Acid 24

B. Unsaturated Fatty Acids

-containing one or more double bonds

-lower melting point

1. Monounsaturated -contains one double bond (Monoethenoid, Monoenoic)

2. Polyunsaturated -two or more double bonds (Polyethenoid, Polyenoic)

3. Eicosanoids -derived from eicosa-polyenoic fatty acids

a. Prostanoids

Prostaglandins -exist in all mammalian tissue

-local hormone w/ physiological role

-synthesized by cyclization of the center carbon

chain in Eicosanoic Fatty Acids to form a

cyclopentane ring

-arachidonic acid is the precursor

Thromboxanes -cyclopentane ring interrupted by Oxygen

-involved in blood clot formation

Prostacyclins

b. Leukotrienes (LTs) -causes bronchoconstriction; asthma

-3rd

group of eicosanoid derivatives formed

c. Lipoxins (LXs) -by Lipoxygenase pathway (LTs, LXs)

18

III. TRIACYLGLYCEROLS (TRIGLYCERIDES)

-main storage forms of fatty acids which are esters of the trihydric alcohol glycerol and fatty acids

-Mono: one fatty acid esterifies with glycerol

-Di: two fatty acids esterifies with glycerol

-carbon 1 and 3 of glycerol are not identical

-1 polar glycerol; 3non polar tails (chains of fatty acids)

IV. OUTLINE OF LIPID CLASSIFICATION

A. Simple Lipids (Ester of fatty acids with various alcohols)

1. Fats -esters of fatty acids + glycerol

-includes Oils (liquid state)

2. Waxes -Esters of fatty acids + Higher Weight Monohydric alcohols

B. Complex Lipids (Esters of Fatty Acids containing other groups)

1. Phospholipids -lipids containing a Phosphoric Acid Residue

a. Glycerophospholipids / Phosphoglycerides (glycerol as parent)

Phosphatidyl Serine (-1)

Phosphatidyl Ethanol Amine (0)

Phosphatidyl Choline (0)

Phosphatidyl Inositol (-1)

Plasmalogens

Cardiolipin / Diphosphotidol Glycerol

Lysophospholipids

b. Sphingophospholipids (Sphingosine as parent)

Ceramide

Sphingomyelin

2. Glycolipids -also called Glycosphingolipids

-contains fatty acids + sphingosine + Carbohydrate

Cerebroside

Globoside

Ganglioside

Glycosphingolipids

Galactosylceramide

3. Other Complex Lipids-such as Folipids and Aminolipids

C. Precursor and Derived Lipids

1. Fatty Acids

2. Glycerol

3. Steroids (parent compound: Cyclopentanoperhydrophenanthrene)

4. Other Alcohols

5. Fatty Aldehydes

6. Ketone Bodies

7. Hydrocarbons

8. Lipid-Soluble Vitamins (A, D, E)

19

9. Hormones

LIPID CLASSIFICATION

I. PHOSPHOLIPIDS

-main lipid constituents of membrane

-derivatives of Phosphatidic Acids

**Phosphatidic Acid -important intermediate in synthesis of Triacylglerols & Phosphoglycerols

-not found in great quantity in tissues

A. Phosphoglycerides / Glycerophospholipids

-depend on structures attached to Phosphatidic Acid

1. Phosphatidyl Cholines (Lecithin)

-Phosphoacylglycerols containing Choline

-most abundant phospholipids of the cell membrane

**Choline -important in nervous transmission

**Dipalmitoyl Lecithin -effective surfaceactive agent

-constituent of Surfactant Preventing Adherence in lungs

-if absent, it causes Respiratory Distress Syndrome

2. Phosphotidyl Serine / Cephalin (Phosphatic Acid + Serine)

3. Phosphatidyl Ethanolamine

4. Phosphatidylinositol

-precursor of Second Messengers

-important constituent of cell membrane phospholipids

-cleaves upon stimulation into: Diacylglycerol and Inositol Triphosphate

-both acts as internal signals or second messengers

5. Plasmalogens

-occur in Brain and Muscles

-resemble Phosphatidylethanolamine but has an ether link instead of an ester link

-ester is converted into ether links

6. Cardiolipin / Diphosphotidol Glycerol

-major lipid of mitochondrial membranes

7. Lysophospholipids

-intermediates in the metabolism of Phosphoglycerols

-important in the metabolism and interconversion of phospholipids

-found in oxidized lipoproteins and has been implicated in some of their effects in

promoting Atherosclerosis

20

B. Sphingolipids

-parent structure is an alcohol called Sphingosine

**Sphingosine -long-chain alcohol (similar to glycerol)

-Alcohol + Amino Group in C2 + Long Chain in C3

**Dihydrosphingosine -unsaturation of long chain in C3

--CH=CH- becomes CH2CH2

1. Ceramide

-acid is attached to N-group

-combination of Sphingosine + Fatty Acid

2. Sphingomyelin

-found in the Nervous System (Myelin Sheath)

-upon hydrolysis, it yields to Fatty Acid + Phosphoric Acid + Choline + Complex Amino

Alcohol (Sphingosine)

-polar head is Phosphrylcholine

**Niemman-Pick -Sphingomyelinase degrades Sphingomyelin

-without Sphingomylinase, Sphingomyelin is deposited in the brain

II. GLYCOLIPIDS

-important in Nerve Tissues and in the Cell Membrane

-widely distributed in every tissue of they body, particularly in Nervous tissue (Brain)

-occur particularly in outer leaflet of plasma membrane

-major glycolipids found in animal tissues are glycosphingolipids

A. Glycosphingolipids

-major glycolipids in animal tissues

-contain Ceramide + one or more Sugars

B. Galactosylceramide

-major glycosphingolipid of brain and other nervous tissue

-can be converted to Sulfogalactosylceramide (Sulfatide) present in Myelin

C. Cerebroside

-similar to Ceramide in Sphingolipids, but in C1, there is a sugar

D. Globoside

-similar to Cerebroside, but there are 2 or 3 sugars

E. Ganglioside

-similar to Globoside, but there are more than 3 sugars, complex oligosaccharide

-important because it is responsible for reaction of blood typing

-complex glycosphingolipids derived from Glucosylceramide with Sialic Acid

-present in nervous tissues in high concentrations

-presence of Sugar Derivation called Neuranunic Acid

21

III. CHOLESTEROL

-falls under Sterols (contains a steroid nucleus)

-best known steroid because of its association with Atherosclerosis

-precursor of: Steroids (bile acids, Adrenocortical Hormones, Sex Hormones, D-Vitamins,

Glycosides, Sitosterols, Alkaloids)

-Cyclopentanoperhydro-phenantrene Ring

-3 Hexagonal rings, 1 Penatagonal ring

-18 Carbons

-cell membrane rigidity

-has a rigid Sterol Nucleus (man cant degrade cholesterol which is why it is converted to Bile Acid)

A. Ergosterol

-precursor of Vitamin D

B. Polyprenoids

-share the same parent compound as Cholesterol

-not steroids but related because they are synthesized like cholesterol

1. Ubiquinone -member of respiratory chain in motchondria

2. Dolichol -glycoprotein synthesis bt transferring carbohydrates to asparagines residues

**Isoprenoid Compounds -include Rubber, Camphor, Fat Soluble Vitamin A, D, E, K

22

LECTURE 4: BIOENERGETICS

BIOENERGETICS -also known as Biochemical Thermodynamics

-study of the energy changes accompanying biochemical reactions

-explains how cell synthesis and utilizes energy for the maintenance of cellular homeostasis

-energy changes that are available to perform chemical and physical work keep us alive

**Concepts: Energy and the Thermodynamics Laws it follows

Forms of energy available / unavailable in the cell

Energy trapping system in the cell

I. LAWS OF THERMODYNAMICS

A. Law of Conservation of Energy

-the total energy in a system remains constant

-energy is neither created nor destroyed

-we consume and use energy stored in foods

-the source of energy is the Sun

-ex) Chemical Energy (Food)

Mechanical Energy (contraction of muscles)

Electrical Energy (neurons; trapping of energy)

Heat (Body Temperature)

B. Law of Entropy

-a system and its surroundings always proceed to a state of maximum disorder (maximum

entropy)

-the total entropy of a system must increase if a process is to occur spontaneously

-entropy is the randomness of a system (disordernes)

Gibbs Equation: G = H - TS S = Entropy / Randomness of a system

T = Absolute temperature

H = Enthalpy (Heat content of a compound)

G= Available Energy

**Gibbs Equation -applies to all reactions and processes

-Entropy effect is dependent on temperature (TS)

-if temperature is constant (human body), Enthalpy changes are negligible

23

II. METABOLISM (combined Catabolic + Anabolic Processes)

A. Catabolism vs. Anabolism (types of metabolism) 1. Catabolism -Oxidation Reactions / Exergonic Reactions (generate free energy) -release of Electrons

2. Anabolism -Reduction Reactions / Endergonic Reactions (needs energy) -addition of electrons

B. Oxidation vs. Reduction

1. Oxidation -release on electrons (e + H) -ex) Fe + Fe (+2) + e

FADH2 FAD + 2H(+) + 2es

2. Reduction -addition of electrons in hydrogen -reduction reaction are for synthesis

-ex) Synthesis of glucose from amino acid (not from lipids) NAD + 2H + 2es NADH + H(+)

III. FREE ENERGY (G) -the energy available for useful work; also known as chemical potential

-energy needed for the performance of work

-at equilibrium if G =0

A. Two Types of Reaction

1. Exergonic Reaction -has a negative free energy ( -G) -occurs spontaneously

-free energy is released -occurs with liberation of free energy (trapped by the cell) -termed as Catabolism Reactions

2. Endergonic Reaction -has a positive free energy ( +G)

-non spontaneous (reaction wont occur w/o energy) -needs addition of Energy -termed as Anabolism Reactions

-ex) Benedict’s Test (heat should be added: boiling) B. Coupled Reaction Systems

-endergonic reactions are often coupled with exergonic reactions -requirement: product of first reaction must be the substrate of the second reaction -have a common intermediate: A + C I B + D

-both can undergo completion

-net G is negative

A B Exergonic (-G) A B

B + C D Endergonic (+G)

B+C D C. Standard Free Energy Change (reactions occur in normal conditions) pH=7

C = 37 1 M

A + B C + D Keq = [C] [D] Products **Equilibrium Constant

24

[A] [B] Reactants

IV. STEPS IN HARNESSING ENERGY FROM FOOD

-energy is extracted from food thru oxidation reactions, resulting to formation of CO2 and H2O

-occurs in four stages

-man gets energy needed to drive cellular reactions directly from the oxidation of foods

-man cannot use heat to drive cellular processes

A. Hydrolysis to Monomeric Units (Digestion)

-glucose, amino acids, fats are obtained respectively from carbohydrates, proteins, lipids

B. Conversion to the common intermediate: Acetyl CoA (Absorbtion)

-building blocks are degraded into Acetyl CoA (common intermediate)

-most of the energy contained in metabolic fuel is conserved in Chemical Bonds (electrons)

of Acetyl CoA

C. Degradation of the 2 Carbon Acetyl CoA in the TCA cycle in mitochondria (Redox Reaction) forming CO2

and Reducing Equivalent

-TCA cycle oxidizes Acetyl CoA to CO2

-electron pairs present in the Carbon-Carbon and Carbon-Hydrogen bonds are transferred to

electron carriers (NADH and FADH2)

**TCA Cycle -also known as Tricarboxylic Acid or Krebs Cycle

-localized in the Mitochondria

-Inner Mitochondrial Membrane has enzymes for trapping energy

-excess energy not trapped in chemical bonding during reaction is liberated

as heat

D. Coupling of the TCA cycle to Electron Transport Chain for Synthesis of ATP

-extraction of energy from food is the process of Oxidation Phosphorylation

-energy in electron pairs of NADH and FADH2 is released to Oxygen via Electron Transport

chain and is used for synthesis of ATP

1. The Electron Transport Chain (Energy Trapping System of the Cell)

-composed of specific sequence of Enzymes and their Coenzymes, including NAD

and FAD linked dehydrogenases

-electrons in NADH arise mainly from the Mitochondrial Oxidations

-all of the FADH2 arises from the Mitochonrial Oxidations

2. Synthesis of ATP (Trapping Energy)

25

V. SYNTHESIS OF ATP (Trapping Energy)

-energy stored in ATP (Adenosine Triphosphate) is used to drive cellular processes

-through incorporation of ADP and Pi ATP (7 Kcal / mol)

A. Oxidative Phosphorylation

-Energy needed for Synthesizing Energy = 7.3 Kcal / mol

-flow of electrons from NADH releases sufficient energy to drive ATP synthesis

-Trapping of energy thru Oxidation of ATP in Electron Transport Chain

-food we eat is oxidized and releases free energy which is used to synthesize ATP

-more efficient because more ATP is synthesized

B. Substrate Level Phosphorylation

-synthesis of ATP through High Energy Compounds

-cleaving of bonds (should be higher than 7 Kcal / mol) releases Free Energy

-only one ATP is produced in one substrate level phosphorylation reaction

**High Energy Compounds

-broken and energy is released for ATP synthesis

-has groups that are Labile (easily broken)

1. Phosphoenol Pyruvate -enol has a double bond and alcohol metabolite of

phosphoenol pyruvic acid

2. 1,3-Bisphosphoglycerate -metabolite of glycolysis

3. Creatine Phosphate -skeletal muscles

-Creatine Creatinine

4. Pyrophosphate

**Low Energy Compounds

1. Glucose 1-Phosphate

2. Fructose 6-Phosphate

3. AMP

4. Glucose 6-Phosphate

5. Glycerol 3-Phosphate

**ATP (Adenosine Triphosphate)

-ATP can be cleaved in two ways:

Cleaved to AMP + PPi 2 Pi

Pi + ADP