Nivaldo J. Tro

http://www.cengage.com/chemistry/tro

Mark Erickson • Hartwick College

Chapter 16Biochemistry and

Biotechnology

Brown Hair, Blue Eyes, and Big Mice

• The study of genes has increased our understanding of how we think, how we behave, and what diseases we might have a genetic predisposition to develop.

• We understand not only how a molecular sequence works, but how to take it from one organism and implant it in another.

• Four types of molecules in living organisms– Lipids– Carbohydrates– Proteins– Nucleic acids

a lipid

• Lipids are cellular components that are insoluble in water, but extractable in nonpolar solvents.– Fats, oils, fatty acids, steroids, and some vitamins

• They form the structural components of biological membranes and reservoirs for long-term energy storage.

• They contain twice as much energy per gram as any other class of biochemical compounds.– Efficient energy storage

Lipids and Fats

Fatty Acids• One type of lipid

• Organic acid with a long hydrocarbon tail

• General formula RCOOH

Lipids and Fats

Triglycerides• Fats and oils are a chemical

combination of glycerol and three fatty acids.

Tristearin• Structure/property relationships

– Long hydrocarbon chains: Nonpolar, immiscible with water

– Energy is extracted via oxidation of these long chains (as in gasoline).

– Chains are saturated: Efficient packing, solids

– Fat is conveniently stored in the body.

• Provides thermal insulation

Triolein• Main component of olive oil

• Double bonds in R groups interfere with efficient packing, lowering the melting point and making it a liquid at room temperature.

Trilinolenin

• Polyunsaturated fat: Multiple double bonds in the hydrocarbon chains– Animal fats tend to be saturated.– Plant fats tend to be unsaturated.

• Variations in structure serve different purposes in the human body.

Concept Check 16.1• What is the difference between fats/oils and fatty

acids.

Concept Check 16.1 Solution• Fatty acids are components of fats. Fats are

triglycerides (glycerol triesters) of three fatty acids (long chain carboxylic acids greater than 12 carbons).

CH3(CH2)16COH

O

3

stearic acid(a saturated fatty acid)

+

CH2OH

CHOH

CH2OH

glycerine

CH2OC(CH2)16CH3

CHOC(CH2)16CH3

CH2OC(CH2)16CH3

a triglyceride (fat)

O

O

O

Concept Check 16.2• Which of the following two triglycerides is expected

to be a liquid at room temperature?

CH2OC(CH2)16CH3

CHOC(CH2)16CH3

CH2OC(CH2)16CH3

O

O

O

CH2OC(CH2)6(CH2CH=CH)3CH2CH3

CHOC(CH2)6(CH2CH=CH)3CH2CH3

CH2OC(CH2)6(CH2CH=CH)3CH2CH3

O

O

O

a.) b.)

Concept Check 16.2 Solution• Triglyceride (b) is an unsaturated fat, therefore,

expected to be a liquid at room temperature.

• Saturated fats are solids at room temperature.

Carbohydrates

• Chemical formulas are multiples of CH2O (carbon-carbo and water-hydrate).

• Function in the body as short-term energy storage

• Chemical structure related to:

• Carbohydrates are polyhydroxy aldehydes, or ketones, or their derivatives.

R OH

alcohols

R CH

O

aldehydes

R C

O

ketones

R

Glucose

• This is a dynamic system, but at any instant more molecules are in the ring form than in the linear form. The formation of a six-membered ring occurs between the —OH at C5 reacting with the aldehyde carbon, C1.

Glucose Properties• Hydroxyl groups mean strong hydrogen bonding with

each other and with water.

• Solubility in body fluids leads to function as a quick energy source.

• Since it is partially oxidized, it yields less energy per gram than octane or lipids of similar carbon content.

• Balance between efficient energy storage and ease of access to that energy

Fructose versus Glucose

• Isomer of glucose; a five-membered ring

• Two CH2OH groups mean it is more soluble in water and sweeter.– Takes less fructose to achieve the same sweetness as

glucose

Concept Check 16.3• Which of the following structures are carbohydrates?

CHO

HHO

HHO

HHO

CH2OH

a.) b.) CH3CH2OH

O OH

H

OHHO

HO

CH2OH

HH

H

c.) d.)

OH

OH

Concept Check 16.3 Solution• Structures (a) and (c) are carbohydrates. They have

formulas of the form Cx(H2O)y.

CHO

HHO

HHO

HHO

CH2OH

a.)

O OH

H

OHHO

HO

CH2OH

HH

H

c.)

C5H10O5 = C5(H2O)5 C6H12O6 = C6(H2O)6

Saccharides• Monosaccharides: Carbohydrates composed of a single

ring

• Disaccharides: Two monosaccharide rings connected to form a single structure.

O O

H

OHHO

HO

CH2OH

HH

H

O OH

H

OHHO

CH2OH

HH

H

O H

OH

OHHO

HO

CH2OH

HH

H

monosaccharide disaccharide

Saccharides• Monosaccharide units building a polysaccharide (complex

carbohydrate

Complex Carbohydrates• Polysaccharides (complex carbohydrates)

– Most common are starch and cellulose– Subtle molecular difference (the oxygen linkage between

rings and subsequent nature of resulting hydrogen bonds) means a dramatic macroscopic result.

– Human enzymes cannot break the bonds between glucose rings.

Intramolecular hydrogen bonds in cellulose prevent hydrogen bonding with water.

Concept Check 16.4• Classify each of the following carbohydrates as a

monosaccharide, disaccharide, or polysaccharide.

a.)O O

H

OHHO

HO

CH2OH

HH

H

b.)O OH

H

OHHO

CH2OH

HH

H

O OH

H

OHHO

HO

CH2OH

HH

H

O O

H

OHHO

CH2OH

HH

H

c.)O O

H

OHHO

CH2OH

HH

H

n

H

OH

HH

H HOOHOH2C

OH

d.)

Concept Check 16.4 Solution

a.)O O

H

OHHO

HO

CH2OH

HH

H

b.)O OH

H

OHHO

CH2OH

HH

H

O OH

H

OHHO

HO

CH2OH

HH

H

O O

H

OHHO

CH2OH

HH

H

c.)O O

H

OHHO

CH2OH

HH

H

n

H

OH

HH

H HOOHOH2C

OH

d.)

monosaccharide

monosaccharide

disaccharide

polyosaccharide

• Compounds (a) and (d) are carbohydrates in their monocyclic form. Carbohydrate (b) has two linked monosaccharide rings. Carbohydrate (c) has many repeating monosaccharide rings.

Proteins• The body CAN

metabolize proteins.

• The body metabolizes proteins ONLY as a last resort.

• Proteins have much more important other work to do in the body.

Protein Functions• Compose much of the physical structure of the body

(muscle, hair, skin)

• Act as enzymes to control chemical reactions

• Act as hormones to regulate metabolic processes

• Transport oxygen from lungs to cells

• Act as antibodies

Protein Functions• Protein molecules are long chains of amino acids.

– Differences among amino acids arise from different R groups.

• Amino acids are molecules that contain both an amine group and a carboxylic acid group. There are only 20 common amino acids.

• Changing the number and order of these amino acids changes the functionality of the protein.

• The simplest R group is the hydrogen atom; the amino acid is glycine.

H2N C COOH

H

R

General formulafor an amino acid

H2N C COOH

H

H

R = H, Glycine

carboxylic acid groupamine group

Concept Check 16.5• Which of the following molecules are amino acids?

CH3CCOH

OH

O

a.) CH3CCOH

NH2

O

b.)

c.) HSCH2CH2COH

O

d.) HOCH2CHCOH

O

NH2

Concept Check 16.5 Solution• Amino acids have the general structure, where the amino and

carboxyl groups are attached to the same carbon:

• Compounds (b) and (d) are amino acids.

CH3CCOH

NH2

O

b.)d.) HOCH2CHCOH

O

NH2

amino acidamino acid

COH

O

C

NH2

R

H

amino group (amine)

carboxyl group (carboxylic acid)

The Peptide Bond• The acidic end of one amino acid reacts with the

amine side of another to form a peptide bond.

• Two linked amino acids is called a dipeptide.

• Chains with 50 units or less are polypeptides; chains with over 50 units are called proteins.

Concept Check 16.6• Draw the tripeptide that results from a cysteine in the

middle with an alanine on each side.

Concept Check 16.6 Solution• The tripeptide is built as follows:• The formation of the peptide bond is a condensation

reaction (See Chapter 15).

H2N C

H

CH2SH

C

O

OH H2N C

H

CH3

C

O

OHH2N C

H

CH3

C

O

OH

Alanine Cysteine Alanine

N C

H

CH2SH

C

O

N C

H

CH3

C

O

OHH2N C

H

CH3

C

O H H

tripeptide

Sickle Cell Anemia• Hemoglobin (Hb) is a medium-size protein with a molecular

formula that contains close to 10,000 atoms: C2952H4664O832S8Fe4

• Replacing polar glutamate with nonpolar valine at one position on two of these chains lowers the solubility of Hb, resulting in red blood cell deformation. The deformed blood cells block the flow of blood to capillaries.

Protein Structure• The structure of a protein is finely tuned to achieve a specific

function.

• We characterize protein structure in four categories:

– Primary

– Secondary

– Tertiary

– Quaternary

Primary Structure• The amino acid sequence held together by peptide bonds

• Abbreviations like “Gly-Val-Ala-Asp” are used to describe the sequence of the amino acids.

N C

H

CH2SH

C

O

N C

H

CH3

C

O

OHH2N C

H

CH3

C

O H H

tripeptide Ala-Cys-Ala

Secondary Structure• The way the amino acid

chain orients itself along its axis

• Common secondary structures– Alpha-helix

– Pleated sheet

Alpha-Helix• Helical shape is maintained by hydrogen bonds between

different amino acids along the protein chain.

• α-keratin is an alpha-helix and is responsible for the elasticity of hair and wool.

• It works like a spring.

Pleated Sheet• Protein forms zigzag

chains that stack neatly together.

• Silk is a pleated sheet

• Inelasticity due to full extension of protein chains

• Softness due to sliding of sheets past each other

Tertiary and Quaternary Structures• Tertiary structure is the bending and folding due to interactions

between amino acids on the chain.– Completely extended– Globular or ball-like

• Overall shape of the particular protein strand• The arrangement of subunits of the protein chain in space is

the quaternary structure.

Interactions Responsible for Protein Tertiary and Quaternary Structure

The tertiary and quaternary structures of proteins are maintained by four kinds of interactions between R groups on different parts of the protein strand:

• Hydrogen bonding• Hydrophobic interactions• Salt bridges• Disulfide linkages

Common Proteins: Hemoglobin (Hb)• Entire structure not known until

late 1950s• Hb folds to hold four flat

molecules called heme groups.– Picks up oxygen at lungs– Releases it at cells

undergoing glucose oxidation• Interior of Hb molecule is highly

nonpolar.– Repels water– Allows oxygen in and out

• Exterior is polar– Hemoglobin is soluble in

water.

α-Keratin• Composes hair and wool

• α-helix structure maintained by hydrogen bonding

• Hair

– Three α-helices in a coil held together by hydrogen bonds and disulfide linkages, which upon chemical treatment can easily break and reform.

Lysozyme

• Acts as an enzyme

• Cleaves polysaccharide units within cell walls

– Walls explode, killing the bacteria

• Found in nasal mucus and tears

• Discovered by Alexander Fleming in 1922

Insulin• Acts as a hormone

• Synthesized in the pancreas

• Small (51 amino acids)

• Promotes entry of glucose into muscle and fat cells, lowering blood glucose level

• Diabetics may have to inject insulin.

Nucleic Acids• The templates from which all proteins are made

• Two types

– DNA (deoxyribonucleic acid)

• Occurs primarily in the cell information center (nucleus)

– RNA (ribonucleic acid)

• Occurs throughout interior of cells

Nucleotides• Phosphate and sugar groups are

identical in every nucleotide, the monomer of nucleic acids.

• Four different bases– A, adenine– T, thymine– C, cytosine– G, guanine

• Codon– A group of three bases that

codes for one amino acid• With minor exceptions, the code is

universal; it is identical in all organisms, from bacteria to humans.

DNA• Occurs in chromosomes, found

in the nucleus of most cells of the human body– There are 46 chromosomes

in humans.• Each set of DNA contains all

the DNA required to specify an entire person.– Organs make those proteins

specific for their own functioning.

– The blueprint is there in each cell with a nucleus for everything else too.

DNA Replication• Mechanism elucidated by Watson,

Crick, and Franklin in 1953

• Complementary base units are formed (with the help of enzymes) after the double-helix unzips.

– Two daughter DNA strands formed

• Daughter DNA molecules are identical in every way to the parent.

A pairs with TC pairs with G

Concept Check 16.7• Draw the complementary strand for the DNA shown.

C C A T G A

Concept Check 16.7 Solution• In the complementary strand, adenine (A) pairs with

thymine (T) and cytosine (C) pairs with guanine (G).

C C A T G A

G G T A C Tcomplementary strand

Protein Synthesis• Genes are sections of DNA thousands of base pairs long.• When the gene for a protein is needed, that section of DNA

unwinds.• A messenger RNA (mRNA) is formed, which is a complement

to the unwound section. • Expression

• mRNA goes to a ribosome where protein synthesis occurs.• Cells express only the proteins specific to their function.

Viruses• Definition lies somewhere between life and

nonlife.– Difficult to kill, do not respond to antibiotics

• Require the machinery of a host cell to reproduce– Virus inserts it own DNA into the chromosomes

of the host.– Host then expresses viral DNA.

• Common cold, flu, measles, polio, smallpox, and ebola are examples of viruses.

AIDS• HIV causes AIDS.• HIV attacks immune system

cells, releasing its RNA.• Reverse transcriptase forms

viral DNA from the RNA.• An enzyme inserts the DNA

into the chromosomes of the host cell.

• Immune system cell dies, releasing daughter HIVs and the cycle repeats destroying the cells of the immune system,.

Recombinant DNA Technology• Employs restriction enzymes that

cut DNA in specific places• DNA pieces can be separated by

gel electrophoresis.– Even single genes can be

isolated.• A DNA strand from one organism

(a human) can be introduced into another (a bacterium).

• Bacterium are cultured, replicating DNA.

• This is also a source for the protein coded for by that DNA.

Pharmaceuticals• Insulin

– Animal insulin is not tolerated by all diabetics.

– The gene that codes for the production of human insulin was copied and expressed by a bacterium.

– Human insulin factory

– Most diabetics take genetically engineered insulin today.

• Human growth hormone (HGH)

– Developed with recombinant DNA technology

– Some children make insufficient amounts of this protein and fail to grow to normal adult size.

Agriculture

• Bacteria without the protein that accelerates ice crystal formation on crop leaves have been engineered.

• What impacts might this (and similar technologies) have on the environment?

Genetic Screening and Disease Therapy

• We can screen for genes that may indicate predisposition to disease.– Should insurance companies have access to this

information?

• Genetic engineering techniques might one day be used to treat genetic disease directly.– Cystic Fibrosis (CF)– Huntington’s disease– Muscular Dystrophy (MD)

Cloning• When egg DNA is modified,

whole new organisms can develop.

• Science fiction is now possible in reality.

• Embryonic cloning has been achieved in animals.

• By nuclear transfer, cloning of adult organisms has been achieved in animals.

Nuclear transfer technique

Therapeutic Cloning and Stem Cells

• Reproductive cloning is generally viewed as unethical.

• Therapeutic cloning is regarded as acceptable.– Goal is to produce embryonic stem cells that are

genetically identical to the adult donor– These are the master cells normally present in embryos

days after the fertilization of an egg.

• Therapeutic cloning offers the potential to make embryonic stem cells that are a perfect genetic match to the donor of the DNA from whom the stem cells are cloned.– Stem cells are the master cells that can become any cell.– No rejection by the immune system– Fraught with controversy

Concept Check 16.8What might some of the ethical issues associated with

embryonic stem cells

Concept Check 16.8 IdeasPros:• Embryonic stem cells can become any cell in the human body

such as liver, brain, and heart cells making organ tissue regeneration possible.

• No chance of tissue and organ rejection because the new cells will have an exact DNA match.

• Cure degenerative diseases such as Parkinson’s disease.

Cons:• Religious and ethical objections to ending potential life to

harvest embryonic stem cells.• Current laws and ethical guidelines have not caught up with

rapidly evolving science and technology.

Chapter SummaryMolecular Concept

• Lipids

• Carbohydrates

• Proteins

• Nucleic acids

Societal Impact

• The chemical study of the molecules that compose life has led to incredible advances in medicine, agriculture, and other related technologies.

• Scientists have also modified the DNA in fertilized eggs to produce genetically engineered organisms.

• Cloning