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10 Focus on Health & Medicine: Using Enzymes to Diagnose and Treat Diseases

10 Focus on Health & Medicine: Using Enzymes to Diagnose and Treat Diseases

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FOCUS ON HEALTH & MEDICINE: USING ENZYMES TO DIAGNOSE AND TREAT DISEASES



21.10B



675



TREATING DISEASE WITH DRUGS THAT INTERACT

WITH ENZYMES



Molecules that inhibit an enzyme can be useful drugs. The antibiotics penicillin and sulfanilamide are two examples discussed in Section 21.9. Drugs used to treat high blood pressure and

acquired immune deficiency syndrome (AIDS) are also enzyme inhibitors.

ACE inhibitors are a group of drugs used to treat individuals with high blood pressure. Angiotensin is an octapeptide that narrows blood vessels, thus increasing blood pressure. Angiotensin

is formed from the zymogen angiotensinogen by action of ACE, the angiotensin-converting

enzyme, which cleaves two amino acids from the inactive decapeptide.

ACE cleaves here.

Arg–Arg–Val–Tyr–Ile–His–Pro–Phe–His–Leu



Arg–Arg–Val–Tyr–Ile–His–Pro–Phe



+



His–Leu



angiotensin



angiotensinogen



increases blood pressure



HEALTH NOTE



By blocking the conversion of angiotensinogen to angiotensin, blood pressure is decreased.

Several effective ACE inhibitors are currently available, including captopril and enalapril.

COO−



COO−



O

HSCH2



CH



C



CH2CH2



N



COO−



CH3

Generic name: captopril

Trade name: Capoten



ACE inhibitors such as lisinopril

(trade name: Zestril) decrease the

concentration of angiotensin, thus

decreasing blood pressure.



CH



H

N



O

CH



C



N



CH3



Generic name: enalapril

Trade name: Vasotec



Several enzyme inhibitors are also available to treat human immunodeficiency virus (HIV), the

virus that causes AIDS. The most effective treatments are HIV protease inhibitors. These drugs

inhibit the action of the HIV protease enzyme, an essential enzyme needed by HIV to make

copies of itself that go on to infect other cells. Deactivating the HIV protease enzyme decreases

the virus population, bringing the disease under control. Several protease inhibitors are currently

available, and often an individual takes a “cocktail” of several drugs to keep the disease in check.

Amprenavir (trade name: Agenerase) is a protease inhibitor taken twice daily by individuals who

are HIV positive. The three-dimensional structure of the HIV-1 protease enzyme is shown in

Figure 21.16.

O

H2N



S

O



CH2CH(CH3)2

NCH2



CH

OH



O

CH



H

N



C



O



O



CH2



Generic name: amprenavir

Trade name: Agenerase



PROBLEM 21.28



smi26573_ch21.indd 675



How are the structures of the ACE inhibitors captopril and enalapril similar? How are they

different?



12/16/08 2:04:15 PM



676







AMINO ACIDS, PROTEINS, AND ENZYMES



FIGURE 21.16



The HIV Protease Enzyme



a. Ball-and-stick model of the HIV protease enzyme



b. Ribbon diagram with the protease inhibitor

amprenavir in the active site



CHAPTER HIGHLIGHTS

KEY TERMS

Active site (21.9)

Amino acid (21.2)

Coenzyme (21.9)

Cofactor (21.9)

Competitive inhibitor (21.9)

Conjugated protein (21.7)

C-Terminal amino acid (21.4)

Denaturation (21.8)

Dipeptide (21.4)

Enzyme (21.9)

Enzyme–substrate complex (21.9)

Fibrous protein (21.7)



Globular protein (21.7)

α-Helix (21.6)

Heme (21.7)

Induced-fit model (21.9)

Inhibitor (21.9)

Irreversible inhibitor (21.9)

Isoelectric point (21.3)

Lock-and-key model (21.9)

Noncompetitive inhibitor (21.9)

N-Terminal amino acid (21.4)

Peptide (21.4)

Peptide bond (21.4)



β-Pleated sheet (21.6)

Primary structure (21.6)

Protein (21.1)

Quaternary structure (21.6)

Reversible inhibitor (21.9)

Secondary structure (21.6)

Tertiary structure (21.6)

Tripeptide (21.4)

Zwitterion (21.2)

Zymogen (21.9)



KEY CONCEPTS

❷ Describe the acid–base properties of amino acids. (21.3)

❶ What are the main structural features of an amino acid?

(21.2)

• Neutral, uncharged amino acids exist as zwitterions

• Amino acids contain an amino group (NH2) on the α carbon

containing an ammonium cation (–NH3+) and a carboxylate

to the carboxyl group (COOH). Because they contain both

anion (–COO–).

an acid and a base, amino acids exist in their neutral form as

• When strong acid is added, the carboxylate anion gains a

zwitterions having the general structure +H3NCH(R)COO–.

proton and the amino acid has a net +1 charge. When strong

Because they are salts, amino acids are water soluble and

base is added, the ammonium cation loses a proton and the

have high melting points.

amino acid has a net –1 charge.

• All amino acids except glycine (R = H) have a

H

H

H

chirality center on the α carbon. l Amino acids

−OH

+

+

H+



H3N C COOH

H3N C COO

H2N C COO−

are naturally occurring.

• Amino acids are subclassified as neutral, acidic,

CH3

CH3

CH3

or basic by the functional groups present in the

overall −1 charge

overall +1 charge

R group, as shown in Table 21.2.

pH < 2



smi26573_ch21.indd 676



pH ≈ 6



pH > 10



12/16/08 2:04:17 PM



CHAPTER HIGHLIGHTS



❸ What are the main structural features of peptides? (21.4)

• Peptides contain amino acids, called amino acid residues,

joined together by amide (peptide) bonds. The amino acid

that contains the free –NH3+ group on the α carbon is called

the N-terminal amino acid, and the amino acid that contains

the free –COO– group on the α carbon is the C-terminal

amino acid.

• Peptides are written from left to right, from the N-terminal

to the C-terminal end, using the one- or three-letter

abbreviations for the amino acids listed in Table 21.2.

❹ Give examples of simple biologically active peptides. (21.5)

• Enkephalins are pentapeptides that act as sedatives and pain

killers by binding to pain receptors.

• Oxytocin is a nonapeptide hormone that stimulates the

contraction of uterine muscles and initiates the flow of milk

in nursing mothers.

• Vasopressin is a nonapeptide hormone that serves as an

antidiuretic; that is, vasopressin causes the kidneys to retain

water.

❺ What are the general characteristics of the primary,

secondary, tertiary, and quaternary structure of proteins?

(21.6)

• The primary structure of a protein is the particular sequence

of amino acids joined together by amide bonds.

• The two most common types of secondary structure are

the α-helix and the β-pleated sheet. Both structures are

stabilized by hydrogen bonds between the N H and C O

groups.

• The tertiary structure is the three-dimensional shape adopted

by the entire peptide chain. London dispersion forces

stabilize hydrophobic interactions between nonpolar amino

acids. Hydrogen bonding and ionic interactions occur

between polar or charged amino acid residues. Disulfide

bonds are covalent sulfur–sulfur bonds that occur between

cysteine residues in different parts of the peptide chain.

• When a protein contains more than one polypeptide chain,

the quaternary structure describes the shape of the protein

complex formed by two or more chains.

❻ What are the basic features of fibrous proteins like

𝛂-keratin and collagen? (21.7)

• Fibrous proteins are composed of long linear polypeptide

chains that serve structural roles and are water insoluble.

• α-Keratin in hair is a fibrous protein composed almost

exclusively of α-helix units that wind together to form

a superhelix. Disulfide bonds between chains make the

resulting bundles of protein chains strong.

• Collagen, found in connective tissue, is composed of a

superhelix formed from three elongated left-handed helices.



smi26573_ch21.indd 677



677



❼ What are the basic features of globular proteins like

hemoglobin and myoglobin? (21.7)

• Globular proteins have compact shapes and are folded to

place polar amino acids on the outside to make them water

soluble. Hemoglobin and myoglobin are both conjugated

proteins composed of a protein unit and a heme molecule.

The Fe2+ ion of the heme binds oxygen. While myoglobin

has a single polypeptide chain, hemoglobin contains four

peptide chains that form a single protein molecule.

❽ What products are formed when a protein is hydrolyzed?

(21.8)

• Hydrolysis breaks up the primary structure of a protein

to form the amino acids that compose it. All of the amide

bonds are broken by the addition of water, forming a

carboxylate anion (–COO–) in one amino acid and an

ammonium cation (–NH3+) in the other.

❾ What is denaturation? (21.8)

• Denaturation is a process that alters the shape of a protein

by disrupting the secondary, tertiary, or quaternary

structure. High temperature, acid, base, and agitation can

denature a protein. Compact water-soluble proteins uncoil

and become less water soluble.

❿ What are the main structural features of enzymes? (21.9)

• Enzymes are biological catalysts that greatly increase the

rate of biological reactions and are highly specific for a

substrate or a type of substrate. An enzyme binds a substrate

at its active site, forming an enzyme–substrate complex by

either the lock-and-key model or the induced-fit model.

• Enzyme inhibitors cause an enzyme to lose activity.

Irreversible inhibition occurs when an inhibitor covalently

binds the enzyme and permanently destroys its activity.

Competitive reversible inhibition occurs when the inhibitor

is structurally similar to the substrate and competes with it

for occupation of the active site. Noncompetitive reversible

inhibition occurs when an inhibitor binds to a location other

than the active site, altering the shape of the active site.

⓫ How are enzymes used in medicine? (21.10)

• Measuring blood enzyme levels is used to diagnose

heart attacks and diseases that cause higher-than-normal

concentrations of certain enzymes to enter the blood.

• Drugs that inhibit the action of an enzyme can be used to

kill bacteria. ACE inhibitors are used to treat high blood

pressure. HIV protease inhibitors are used to treat HIV by

binding to an enzyme needed by the virus to replicate itself.



12/16/08 2:04:18 PM



678



AMINO ACIDS, PROTEINS, AND ENZYMES



PROBLEMS

Selected in-chapter and end-of-chapter problems have brief answers provided in Appendix B.



Amino Acids

21.29

21.30

21.31



21.32



21.33



21.34



21.35

21.36

21.37



21.38



21.39



Naturally occurring amino acids are l-α-amino acids.

What do the l and α designations represent?

Why do neutral amino acids exist as zwitterions with no

net charge?

The amino acid alanine is a solid at room temperature

and has a melting point of 315 °C, while pyruvic acid

(CH3COCO2H) has a similar molecular weight but is a

liquid at room temperature with a boiling point of 165 °C.

Account for the difference.

Why is phenylalanine water soluble but 4-phenylbutanoic

acid (C6H5CH2CH2CH2COOH), a compound of similar

molecular weight, water insoluble?

Draw the structure of a naturally occurring amino acid

that:

a. contains a 1° alcohol

b. contains an amide

c. is an essential amino acid with an aromatic ring

d. is a neutral amino acid with a 3° carbon atom in its

side chain

Draw the structure of a naturally occurring amino acid

that:

a. contains a 2° alcohol

b. contains a thiol

c. is an acidic amino acid

d. is a neutral amino acid with a phenol in the side chain

What two amino acids contain two chirality centers?

What makes proline different from all of the other amino

acids in Table 21.2?

For each amino acid: [1] draw the l enantiomer in a

Fischer projection; [2] classify the amino acid as neutral,

acidic, or basic; [3] give the three-letter symbol; [4] give

the one-letter symbol.

a. leucine

c. lysine

b. tryptophan

d. aspartic acid

For each amino acid: [1] draw the l enantiomer in a

Fischer projection; [2] classify the amino acid as neutral,

acidic, or basic; [3] give the three-letter symbol; [4] give

the one-letter symbol.

a. arginine

c. glutamic acid

b. tyrosine

d. valine

Draw both enantiomers of each amino acid and label

them as d or l: (a) methionine; (b) asparagine.



smi26573_ch21.indd 678



21.40



Which of the following Fischer projections represent

naturally occurring amino acids? Name each amino acid

and designate it as a d or l isomer.

COO−



a.



+



H3N



H



COO−



c.



+



H3N



CH2CH(CH3)2



H

+



CH2CH2CH2CH2NH3



COO−



b.



+



H



NH3

CH2COO−



21.41



For each amino acid: [1] give the name; [2] give

the three-letter abbreviation; [3] give the one-letter

abbreviation; [4] classify the amino acid as neutral,

acidic, or basic.

COO−



a.



+



H3N



H



COO−



c.



+



H3N



H

OH



CH2



CH2CH2CONH2

COO−



b.



+



H3N



H

CH(OH)CH3



21.42



For each amino acid: [1] give the name; [2] give

the three-letter abbreviation; [3] give the one-letter

abbreviation; [4] classify the amino acid as neutral,

acidic, or basic.

COO−



COO−



a.



+



H3N



H

CH2CH2SCH3



c.



+



H3N



H

N



CH2

HN



COO−



b.



+



H3N



H

CH2OH



Acid–Base Properties of Amino Acids

21.43



21.44



21.45



Draw the amino acid leucine at each pH: (a) 6; (b) 10;

(c) 2. Which form predominates at leucine’s isoelectric

point?

Draw the amino acid isoleucine at each pH: (a) 6; (b) 10;

(c) 2. Which form predominates at isoleucine’s isoelectric

point?

Draw the structure of the neutral, positively charged,

and negatively charged forms of the amino acid tyrosine.

Which form predominates at pH 1? Which form

predominates at pH 11? Which form predominates at the

isoelectric point?



12/16/08 2:04:19 PM



PROBLEMS



21.46



679



Draw the structure of the neutral, positively charged, and

negatively charged forms of the amino acid valine. Which

form predominates at pH 1? Which form predominates at

pH 11? Which form predominates at the isoelectric point?



21.52



a.



21.48



21.49



21.50



21.51



(a) Draw the structure of the two possible dipeptides that

can be formed by combining valine and phenylalanine.

(b) In each dipeptide, label the N- and C-terminal amino

acids. (c) Name each peptide using three-letter symbols.

(a) Draw the structure of the two possible dipeptides that

can be formed by combining glycine and asparagine.

(b) In each dipeptide, label the N- and C-terminal amino

acids. (c) Name each peptide using three-letter symbols.

For each tripeptide: [1] draw the structure of the

tripeptide; [2] label the amide bonds; [3] identify the

N-terminal and C-terminal amino acids; [4] name the

peptide using three-letter symbols for the amino acids.

a. leucylvalyltryptophan

b. alanylglycylvaline

c. phenylalanylserylthreonine

For each tripeptide: [1] draw the structure of the

tripeptide; [2] label the amide bonds; [3] identify the

N-terminal and C-terminal amino acids; [4] name the

peptide using three-letter symbols for the amino acids.

a. tyrosylleucylisoleucine

b. histidylglutamyllysine

c. methionylisoleucylcysteine

For each tripeptide: [1] identify the amino acids that form

the peptide; [2] label the N- and C-terminal amino acids;

[3] name the tripeptide using three-letter symbols.

O



O



a.



+



H3N



CH



C



N



CH(CH3)2 H



CH

H



b.



H3N



CH



C



CH2



N

H



CH



N



CH



H



CH2



C



C



C



O−



N



CH



H



CH2CH2SCH3



CH



C



N



CH



H



CH3



C



b.



21.53



21.54



21.55

21.56

21.57



+



H3N



CH



C



N



CH



CH2OH



H



CH2



CH



H



CH(CH3)CH2CH3



C



O

C



O−



N



CH



H



CH2CH2CONH2



Draw the structure of the three different tripeptides

formed from two moles of serine and one mole of

alanine.

How many different tripeptides can be formed from

three different amino acids, methionine, histidine, and

arginine? Using three-letter abbreviations, give the names

for all of the possible tripeptides.

Draw the structures of the amino acids formed when the

tripeptides in Problem 21.51 are hydrolyzed.

Draw the structures of the amino acids formed when the

tripeptides in Problem 21.52 are hydrolyzed.

Bradykinin is a nonapeptide that stimulates smooth

muscle contraction, dilates blood vessels, causes pain,

and is a component of bee venom. Draw the structure

of the amino acids formed on hydrolysis of one mole of

bradykinin, and tell how many moles of each amino acid

are formed.

Arg–Pro–Pro–Gly–Phe–Ser–Pro–Phe–Arg

bradykinin



Aspartame, the methyl ester of a dipeptide, is the common

artificial sweetener NutraSweet (Section 20.5B). Draw the

structure of the products formed when the amide and ester

bonds are hydrolyzed. Which amino acid contains the

carbonyl group of the peptide bond? Which amino acid

contains the nitrogen atom of the amide bond?



CH(CH3)2



O



O

+



H3N

OH



C



O−



N



O



O



21.58

O



H3N



O



COO−



O−



CH2



+



CH2



O



O



O

+



C



O



O



Peptides

21.47



For each tripeptide: [1] identify the amino acids that form

the peptide; [2] label the N- and C-terminal amino acids;

[3] name the tripeptide using three-letter symbols.



CH



C



CH2

COO−



N

H



CH



C



OCH3



CH2



aspartame



smi26573_ch21.indd 679



12/16/08 2:04:19 PM



680



21.59



21.60



AMINO ACIDS, PROTEINS, AND ENZYMES



Chymotrypsin is a digestive enzyme that hydrolyzes only

certain peptide bonds: the carbonyl group in the amide

bond must come from phenylalanine, tyrosine, tryptophan,

or methionine. Draw the structure of the amino acids and

peptides formed by hydrolysis of the following peptide

with chymotrypsin: Gly–Tyr–Gly–Ala–Phe–Val.

Trypsin is a digestive enzyme that hydrolyzes peptide bonds

only when the carbonyl group in the amide bond comes

from lysine or arginine. Draw the structure of the amino

acids and peptides formed by hydrolysis of the following

peptide with trypsin: Gly–Lys–Arg–Ala–Ala–Arg.



21.70



Label the regions of secondary structure in the following

protein ribbon diagram.



21.71



Compare α-keratin and hemoglobin with regards to

each of the following: (a) secondary structure; (b) water

solubility; (c) function; (d) location in the body.

Compare collagen and myoglobin with regards to each

of the following: (a) secondary structure; (b) water

solubility; (c) function; (d) location in the body.

When a protein is denatured, how is its primary,

secondary, tertiary, and quaternary structure affected?

Hydrogen bonding stabilizes both the secondary and

tertiary structures of a protein. (a) What functional groups

hydrogen bond to stabilize secondary structure? (b) What

functional groups hydrogen bond to stabilize tertiary

structure?

Describe the function or biological activity of each

protein or peptide: (a) insulin; (b) myoglobin;

(c) α-keratin; (d) chymotrypsin; (e) oxytocin.

Describe the function or biological activity of each

protein or peptide: (a) collagen; (b) hemoglobin;

(c) vasopressin; (d) pepsin; (e) met-enkephalin.



Proteins

21.61

21.62

21.63



21.64



21.65



21.66



21.67

21.68

21.69



What is the difference between the primary and

secondary structure of a protein?

What is the difference between the tertiary and quaternary

structure of a protein?

What type of intermolecular forces exist between the side

chains of each of the following pairs of amino acids?

a. isoleucine and valine

c. Lys and Glu

b. threonine and phenylalanine

d. Arg and Asp

Which of the following pairs of amino acids can have

intermolecular hydrogen bonding between the functional

groups in their side chains?

a. two tyrosine residues

c. phenylalanine and tyrosine

b. serine and threonine

d. alanine and threonine

Draw the structures of the amino acids asparagine and

serine and show how hydrogen bonding is possible

between the two side chains.

Draw the structures of the amino acids tyrosine and

threonine and show how hydrogen bonding is possible

between the two side chains.

List four amino acids that would probably be located in

the interior of a globular protein.

List four amino acids that would probably be located on

the exterior of a globular protein.

Label the regions of secondary structure in the following

protein ribbon diagram.



21.72



21.73

21.74



21.75



21.76



Enzymes

21.77

21.78

21.79

21.80

21.81



21.82



smi26573_ch21.indd 680



What is the difference between reversible and irreversible

inhibition?

What is the difference between competitive and

noncompetitive inhibition?

Explain the role of zymogens in (a) controlling blood

pressure; (b) the action of digestive enzymes.

What is the difference between a coenzyme and a

cofactor?

How are enzyme inhibitors used to treat high blood

pressure? Give a specific example of a drug used and an

enzyme inhibited.

How are enzyme inhibitors used to treat HIV? Give a

specific example of a drug used and an enzyme inhibited.



12/16/08 2:04:20 PM



PROBLEMS



21.83



681



Use the given representations for an enzyme, substrate,

and inhibitor to illustrate the process of noncompetitive

inhibition.



Applications

21.85

21.86

21.87



active site



21.88

enzyme



21.84



substrate



inhibitor



Use the given representations for an enzyme and substrate

to illustrate the difference between the lock-and-key

model and the induced-fit model of enzyme specificity.



21.89



21.90

21.91

21.92



active site



enzyme



substrate



21.93



21.94



What structural feature in α-keratin makes fingernails

harder than skin?

Why does the α-keratin in hair contain many cysteine

residues?

Why must vegetarian diets be carefully balanced?

Why does cooking meat make it easier to digest?

Sometimes an incision is cauterized (burned) to close the

wound and prevent bleeding. What does cauterization do

to protein structure?

Why is insulin administered by injection instead of taken

in tablet form?

How is sickle cell disease related to hemoglobin

structure?

The silk produced by a silkworm is a protein with a

high glycine and alanine content. With reference to the

structure, how does this make the silk fiber strong?

Explain the difference in the mechanism of action of

penicillin and sulfanilamide. How is enzyme inhibition

involved in both mechanisms? Why don’t penicillin and

sulfanilamide kill both human and bacterial cells?

How are blood enzyme levels used to diagnose certain

diseases? Give an example of a specific condition and

enzyme used for diagnosis.



CHALLENGE QUESTIONS

21.95



smi26573_ch21.indd 681



Explain why two amino acids—aspartic acid and

glutamic acid—have a +1 net charge at low pH, but a –2

net charge at high pH.



21.96



Suggest a reason for the following observation. Proteins

like collagen that are high in proline content do not

contain an α-helix in their secondary structure.



12/16/08 2:04:21 PM



22

CHAPTER OUTLINE

22.1



Nucleosides and Nucleotides



22.2



Nucleic Acids



22.3



The DNA Double Helix



22.4



Replication



22.5



RNA



22.6



Transcription



22.7



The Genetic Code



22.8



Translation and Protein Synthesis



22.9



Mutations and Genetic Diseases



22.10 Recombinant DNA

22.11 FOCUS ON HEALTH & MEDICINE:

Viruses



CHAPTER GOALS

In this chapter you will learn how to:

❶ Draw the structure of nucleosides

and nucleotides

❷ Draw short segments of the nucleic

acids DNA and RNA

❸ Describe the basic features of the

DNA double helix

❹ Outline the main steps of replication

❺ List the three types and functions of

RNA molecules

❻ Explain the process of transcription

❼ Describe the basic elements of the

genetic code

❽ Explain the process of translation

❾ Define the terms “mutation” and

“genetic disease”

❿ Describe the basic features of

recombinant DNA, the polymerase

chain reaction, and DNA fingerprinting

⓫ Describe the main characteristics

of viruses



Techniques to analyze DNA samples are commonly utilized in criminal investigations and to

screen for genetic diseases.



NUCLEIC ACIDS AND

PROTEIN SYNTHESIS

WHETHER you are tall or short, fair-skinned or dark-complexioned, blue-eyed

or brown-eyed, your unique characteristics are determined by the nucleic acid

polymers that reside in the chromosomes of your cells. The nucleic acid DNA

stores the genetic information of a particular organism, while the nucleic acid

RNA translates this genetic information into the synthesis of proteins needed by

cells for proper function and development. Even minor alterations in the nucleic

acid sequence can have significant effects on an organism, sometimes resulting in

devastating diseases like sickle cell anemia and cystic fibrosis. In Chapter 22, we

study nucleic acids and learn how the genetic information stored in DNA is translated into protein synthesis.



682



smi26573_ch22.indd 682



12/19/08 2:15:25 PM



NUCLEOSIDES AND NUCLEOTIDES



683



22.1 NUCLEOSIDES AND NUCLEOTIDES

Nucleic acids are unbranched polymers composed of repeating monomers called nucleotides. There are two types of nucleic acids.

• DNA, deoxyribonucleic acid, stores the genetic information of an organism and transmits

that information from one generation to another.

• RNA, ribonucleic acid, translates the genetic information contained in DNA into proteins

needed for all cellular functions.



The nucleotide monomers that compose DNA and RNA consist of three components—a monosaccharide, a nitrogen-containing base, and a phosphate group.

NH2



A nucleotide

N



N



O

phosphate



−O



P



O



CH2



N



O



N



nitrogen-containing base



O−

OH



monosaccharide



DNA molecules contain several million nucleotides while RNA molecules are much smaller,

containing perhaps a few thousand nucleotides. DNA is contained in the chromosomes of the

nucleus, each chromosome having a different type of DNA. The number of chromosomes differs

from species to species. Humans have 46 chromosomes (23 pairs). An individual chromosome

is composed of many genes. A gene is a portion of the DNA molecule responsible for the

synthesis of a single protein.

We begin our study of nucleic acids with a look at the structure and formation of the nucleotide

monomers.



22.1A



NUCLEOSIDES—JOINING A MONOSACCHARIDE

AND A BASE



The nucleotides of both DNA and RNA contain a five-membered ring monosaccharide, often

called simply the sugar component.

• In RNA, the monosaccharide is the aldopentose D-ribose.

• In DNA the monosaccharide is D-2-deoxyribose, an aldopentose that lacks a hydroxyl

group at C2.



HOCH2



O



OH



5

HOCH2



OH



O



4

OH



OH



D-ribose

(present in RNA)



The prefix deoxy means without

oxygen.



smi26573_ch22.indd 683



1

3

OH



2

no OH at C2



D-2-deoxyribose

(present in DNA)



Only five common nitrogen-containing bases are present in nucleic acids. Three bases with one

ring (cytosine, uracil, and thymine) are derived from the parent compound pyrimidine. Two

bases with two rings (adenine and guanine) are derived from the parent compound purine. Each

base is designated by a one-letter abbreviation as shown.



12/19/08 2:15:33 PM



684



NUCLEIC ACIDS AND PROTEIN SYNTHESIS



NH2



O



O



4

5

6



CH3



N3



N



2



N

1



N

H



pyrimidine

(parent compound)



NH

O



cytosine

C



NH



N

H



O



uracil

U



N



O



6



5



8

9N

H



O



thymine

T



NH2

7



N

H



4 N

3



N1



N



2



N

H



N

N



adenine

A



purine

(parent compound)



N



NH



N

H



N



NH2



guanine

G



Uracil (U) occurs only in RNA, while thymine (T) occurs only in DNA. As a result:

• DNA contains the bases A, G, C, and T.

• RNA contains the bases A, G, C, and U.



A nucleoside is formed by joining the anomeric carbon of the monosaccharide with a nitrogen atom of the base. A nucleoside is an N-glycoside, because it is a nitrogen derivative of the

glycosides discussed in Chapter 20. Primes (') are used to number the carbons of the monosaccharide in a nucleoside, to distinguish them from the atoms in the rings of the base.

NH2

N



NH2

HOCH2



OH



O



OH



+



1

N

H



join



OH



D-ribose



HO



N



5'

CH2



N



O



1

1'



4'

3'



O



2'

OH



OH



O

N-glycoside



cytidine

a ribonucleoside



cytosine

C



NH2

N



NH2

HOCH2



O



N



OH



OH

D-2-deoxyribose



N



+

join



HO



CH2



O



9N

1'



9N

H



N

N

N-glycoside



N



adenine

A



OH

deoxyadenosine

a deoxyribonucleoside



With pyrimidine bases, the nitrogen atom at the 1 position bonds with the 1' carbon of the sugar.

With purine bases, the nitrogen atom at the 9 position bonds with the 1' carbon of the sugar. For

example, joining cytosine with ribose forms the ribonucleoside cytidine. Joining adenine with

2-deoxyribose forms the deoxyribonucleoside deoxyadenosine.



smi26573_ch22.indd 684



12/19/08 2:15:35 PM



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