3.

2 Nucleic Acids The Monomers Are Nucleotides

Chemistry Nucleic acids are informational macromolecules and contain
Next, we come to the nucleic acids, macromolecules of para-
Review– nonidentical monomeric units in a specified sequence. The
Nucleic mount importance to the cell because of their role in storing,
Acids: monomeric units of nucleic acids are called nucleotides.
Functions transmitting, and expressing genetic information. Nucleic
of Nucleic
Nucleotides exhibit less variety than amino acids do; DNA and
acids are linear polymers of nucleotides strung together in
Acids RNA each contain only four different kinds of nucleotides.
a genetically determined order that is critical to their role
(Actually, there is more variety than this suggests, especially
as informational macromolecules. The two major types of
in some RNA molecules in which some nucleotides have been
nucleic acids are DNA (deoxyribonucleic acid) and RNA
chemically modified after insertion into the chain.)
(ribonucleic acid). DNA and RNA differ in their chemistry
As shown in Figure 3-15, each nucleotide consists of
and their role in the cell. As the names suggest, RNA contains
a five-carbon sugar to which is attached a phosphate group
the five-carbon sugar ribose in each of its nucleotides, where-
and a nitrogen-containing aromatic base. The sugar is ei-
as DNA contains the closely related sugar deoxyribose. As we
ther D-ribose (in RNA) or D-deoxyribose (in DNA). The phos-
discussed earlier (in Chapter 1), DNA serves primarily as the
phate is joined by a phosphoester bond to the 5′ carbon of
repository of genetic information, whereas RNA molecules
the sugar, and the base is attached to the 1′ carbon. The base
play several different roles in expressing that information—
may be either a purine or a pyrimidine. DNA contains the
that is, in gene regulation and protein synthesis.

BASES
PHOSPHATE
SUGARS
GROUP
Purines Pyrimidines

H H
N O O
HOCH2 O OH H3C H H H
N
N N N
H H H
H H N
H N H N O H N O
HO H H H H
D-deoxyribose (in DNA) Adenine (A) Thymine (T) Uracil (U)
O
(in DNA) (in RNA)
-
O P O
H H
O- O N
HOCH2 O OH H H
N
N N
H H H
H
H H N
N N H N O
HO OH H
H H
D-ribose (in RNA) Guanine (G) Cytosine (C)

NUCLEOTIDE
H H
N
Phosphoester bond H
N
Base
O
5¿ H N O
Phosphate -O
P O CH2 O
group
4¿ Sugar 1¿
O- C C
H H
H C C 2¿ H Nucleic
3¿ Acid
Building
HO OH RNA Blocks
(H) DNA

Figure 3-15 The Structure of a Nucleotide. In RNA, a nucleotide consists of the five-carbon
sugar D-ribose with an aromatic nitrogen-containing base attached to the 1′ carbon and a phosphate group
linked to the 5′ carbon by a phosphoester bond. Carbon atoms in the sugar of a nucleotide are numbered
from 1′ to 5′ to distinguish them from those in the base, which are numbered without the prime. In DNA, the
hydroxyl group on the 2′ carbon is replaced by a hydrogen atom, so the sugar is D-deoxyribose.
82

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 Table 3-4 The Bases, Nucleosides, and Nucleotides of RNA and DNA

RNA DNA

Bases Nucleoside Nucleotide Deoxynucleoside Deoxynucleotide

Purines
Adenine (A) Adenosine Adenosine monophosphate (AMP) Deoxyadenosine Deoxyadenosine monophosphate (dAMP)
Guanine (G) Guanosine Guanosine monophosphate (GMP) Deoxyguanosine Deoxyguanosine monophosphate (dGMP)
Pyrimidines
Cytosine (C) Cytidine Cytidine monophosphate (CMP) Deoxycytidine Deoxycytidine monophosphate (dCMP)
Uracil (U) Uridine Uridine monophosphate (UMP) — —
Thymine (T) — — Deoxythymidine Deoxythymidine monophosphate (dTMP)

purines adenine (A) and guanine (G) and the pyrimidines
cytosine (C) and thymine (T). RNA also has adenine, gua-
nine, and cytosine, but it contains the pyrimidine uracil (U)
in place of thymine. Like the 20 amino acids present in pro-
teins, these five aromatic bases are among the most common
two phosphoester bonds (one bond to each nucleotide). The
polynucleotide formed by this process has an intrinsic di-
rectionality, with a 5′ phosphate group at one end and a 3′
hydroxyl group at the other end. By convention, nucleotide
sequences are always written from the 5′ end to the 3′ end of

small molecules in cells (see Table 3-1, page 67).
Without the phosphate, the remaining base-sugar unit is
called a nucleoside. Each pyrimidine and purine may there-
fore occur as the free base, the nucleoside, or the nucleotide.
Chapter 3
the polynucleotide because this is the direction of nucleic acid
synthesis in cells (see Chapter 17).
Nucleic acid synthesis requires both energy and in-
formation. To provide the energy needed to form each new

| The Macromolecules of the Cell

The appropriate names for these compounds are given in phosphodiester bridge, each successive nucleotide enters as a
Table 3-4. Notice that nucleotides and nucleosides contain- high-energy nucleoside triphosphate. The precursors for DNA
ing deoxyribose are specified by a lowercase “d” preceding the synthesis are therefore dATP, dCTP, dGTP, and dTTP. For RNA
letters identifying the base. synthesis, ATP, CTP, GTP, and UTP are needed. Information is
As the nomenclature indicates, a nucleotide can be required for nucleic acid synthesis because successive incom-
thought of as a nucleoside monophosphate because it is ing nucleotides must be added in a specific, genetically deter-
a nucleoside with a single phosphate group attached to it. mined sequence. For this purpose, a preexisting molecule is
This terminology can be readily extended to molecules with used as a template to specify nucleotide order. For both DNA
two or three phosphate groups attached to the 5′ carbon. and RNA synthesis, the template is usually DNA. Template-
For example, the nucleoside adenosine (adenine plus ribose) directed nucleic acid synthesis relies on precise and predictable
can have one, two, or three phosphates attached and is des-
ignated accordingly as adenosine monophosphate (AMP), Phosphoanhydride bonds H H
adenosine diphosphate (ADP), or adenosine triphos- N
Adenine
phate (ATP). The relationships among these compounds are Phosphoester bond
N
N
shown in Figure 3-16. H
You probably recognize ATP as the energy-rich com- O O O
H N N
pound used to drive various reactions in the cell, including -O P O P O P O CH2 O
the activation of monomers for polymer formation that we
O- O- O- Ribose
encountered in the previous chapter (see Figure 2-16). As this H H
DNA
example suggests, nucleotides play two roles in cells: They are H H
Structure Phosphate groups
Chemistry the monomeric units of nucleic acids, and several of them—
Review– HO OH
Nucleic ATP most notably—serve as intermediates in various energy-
Acids: Adenosine
Structure of
transferring reactions.
Nucleic Adenosine monophosphate (AMP)
Acids
Activity: The Polymers Are DNA and RNA Adenosine diphosphate (ADP)
Structure
of RNA Nucleic acids are linear polymers formed by linking each Adenosine triphosphate (ATP)
and nucleotide to the next through a phosphate group, as shown
DNA Figure 3-16 The Phosphorylated Forms of Adenosine.
in Figure 3-17. Specifically, the phosphate group already
Adenosine occurs as the free nucleoside (a sugar linked to a base)
attached by a phosphoester bond to the 5′ carbon of one
and can also form part of AMP, ADP, and ATP. The bond linking the
nucleotide becomes linked by a second phosphoester bond to first phosphate to the ribose of adenosine is a phosphoester bond,
the 3′ carbon of the next nucleotide. The resulting linkage is whereas the bonds linking the second and third phosphate groups
known as a 3′, 5′ phosphodiester bridge, which consists to the molecule are phosphoanhydride bonds, which liberate two to
of a phosphate group linked to two adjacent nucleotides via three times as much energy compared to a phosphoester bond.
83

M03_HARD7694_09_GE_C03.indd 83 22/02/17 2:37 pm

 O
5¿ end H H
N
OH Uracil
5¿ H N O
O P O CH2
O
O- H H
N
N
OH N
O H Adenine
N N H
O P O CH2
O
O- H H
O
N
5¿ end H3C H
N H N
OH Thymine OH Cytosine
H N O O
5¿ H
O P O CH2 N O
O O P O CH2
O- O
H H
O-
N Guanine
O
N H
N N
O H Adenine OH N
O H H
N N H
O P O CH2 N
CH2 N N
O O P O
Phosphodiester O
bridge O- H H Phosphodiester H
O-
N bridge
3¿
H N
Cytosine OH
O
H O OH
N
O P O CH2
O (b) RNA 3¿ end
O-
Guanine
O
H
N
N
O H H
N N
O P O CH2 N
O
O- H
3¿

OH

(a) DNA 3¿ end

Sugar-phosphate
backbone

Figure 3-17 The Structure of Nucleic Acids. Nucleic acids are linear chains of nucleotides joined together
by 3′, 5′ phosphodiester bridges. The resulting polynucleotide has an intrinsic directionality, with a 5′ end and
Activity:
DNA a 3′ end. For both DNA and RNA, the backbone of the chain is an alternating sugar-phosphate sequence, from
and RNA which the bases stick out.
Structure

base pairing between a template nucleotide and the specific in-
coming nucleotide that can pair with the template nucleotide.
This recognition process depends on an important chem-
ical feature of the purine and pyrimidine bases shown in
Figure 3-18. These bases have carbonyl groups and nitrogen
atoms capable of hydrogen bond formation under appropri-
ate conditions. Complementary relationships between purines
84
and pyrimidines allow A to form two hydrogen bonds with T
(or U) and G to form three hydrogen bonds with C, as shown in
Figure 3-18. This pairing of A with T (or U) and G with C is a
fundamental property of nucleic acids. Genetically, this base
pairing provides a mechanism for nucleic acids to recognize
one another (as we will see in Chapter 18). For now, however,
let’s concentrate on the structural implications.

M03_HARD7694_09_GE_C03.indd 84 22/02/17 2:37 pm

 5¿ end Hydrogen 3¿ end
bonds
OH OH
H CH3
5¿
O P O CH2 H N N H O H
O
O- 3¿
N N H N N
O-
N O
O H2C O P O
H
Adenine Thymine
O

O H3C H

O P O CH2 H H N N H
O
O
O- N N H N N
O-
N O
O H2C O P O
H
Thymine Adenine O

5¿ to 3¿ direction
5¿ to 3¿ direction

O H
H
O P O CH2 H O N H
H N
O
O- N
N N H N O-

Chapter 3
N O
H2C O P O
O H N
O
H

| The Macromolecules of the Cell

Cytosine Guanine
O H
H
O P O CH2 H N O H N H
O
O- N N H N N O-
3¿
N O
N H O H2C O P O
5¿
OH H OH
3¿ end Guanine Cytosine
5¿ end
The Double
Helix Figure 3-18 Hydrogen Bonding in Nucleic Acid Structure. Two hydrogen bonds (blue dots) between
Activity:
Nucleic Acid
adenine and thymine and three hydrogen bonds between cytosine and guanine account for the AT and CG base
Structure pairing of DNA. If one or both strands were RNA instead, the pairing partner for adenine would be uracil (U).

A DNA Molecule Is a Double-Stranded Helix
Activity: One of the most significant biological advances of the twenti-
Heritable
Information: eth century came in 1953 in a two-page article in the scientific
DNA journal Nature. In the article, Francis Crick and James Watson
Video Tutor
Session postulated a double-stranded helical structure for DNA—the
Quiz: DNA
Structure now-famous double helix—that not only accounted for the
known physical and chemical properties of DNA but also sug-
gested a mechanism for replication of the DNA.
The double helix consists of two complementary chains
of DNA twisted together around a common axis to form a
right-handed helical structure that resembles a spiral stair-
case (Figure 3-19). The two chains are oriented in opposite
directions along the helix, with one running in the 5′ S 3′ di-
rection and the other in the 3′ S 5′ direction. The backbone
of each chain consists of sugar molecules alternating with
phosphate groups (see Figure 3-18). The phosphate groups
are charged, and the sugar molecules contain polar hydroxyl
groups. Therefore, it is not surprising that the sugar-phosphate
backbones of the two strands are on the outside of the DNA
helix, where their interaction with the surrounding aque-
ous environment can be maximized. The pyrimidine and pu-
rine bases, on the other hand, are aromatic compounds with
less affinity for water (more hydrophobic). Accordingly, they
are oriented inward away from water, forming the base pairs
that hold the two chains together. Hydrophobic interactions
among the aromatic rings result in base stacking, which helps
to stabilize the structure of the DNA molecule.
To form a stable double helix, the two component strands
must be antiparallel (running in opposite directions). They also
must be complementary, that is, each base in one strand will
pair with one specific base directly across from it in the other
strand. From the pairing possibilities shown in Figure 3-18,
this means that each A must be paired with a T, and each G
with a C. In both cases, one member of the pair is a pyrimi-
dine (T or C) and the other is a purine (A or G). The distance
between the two sugar-phosphate backbones in the double
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 thinner sugar-phosphate backbone. (For a comparison of the
structures of B-DNA and Z-DNA, see Figure 16-8.)
O
RNA structure also depends in part on base pairing, but
Atoms Atoms in bases this pairing is usually between complementary regions within
in backbone the same strand and is much less extensive than the inter-
P
strand pairing of the DNA duplex. Of the various RNA species,
secondary and tertiary structures occur mainly in rRNA and
C tRNA (see Chapter 19). In addition, some infectious viruses
consist of double-stranded RNA held together by hydrogen
bonding between complementary base pairs.
Hydrogen Sugar-phosphate
bonds backbone 5¿
3¿ CONCEPT CHECK 3.2
5¿ 3¿
A T
Like proteins, nucleotides are important informational
macromolecules. How are they similar to proteins and how
G C
do they differ in terms of monomer types and assembly,
C G polymer structure, and cellular functions?
A T
Base pairs

T A
3.3 Polysaccharides
The next group of macromolecules we will consider are the
C G
polysaccharides, which are long-chain polymers of sug-
A T
ars and sugar derivatives. Polysaccharides usually consist of
G C a single kind of repeating unit, or sometimes an alternating
pattern of two kinds. They serve primarily in energy storage
and as cellular structures rather than carrying information.
A T However (as we will see in Chapter 7), shorter polymers called
oligosaccharides, when attached to proteins on the cell surface,
T A
play important roles in cellular recognition of extracellular
C G signal molecules and of other cells. As noted earlier, polysac-
A T charides include the storage polysaccharides starch and glyco-
gen and the structural polysaccharide cellulose. Each of these
polymers contains the six-carbon sugar glucose as its single
A T
repeating unit, but they differ in the nature of the bond be-
G C tween successive glucose units as well as in the presence and
5¿ extent of side branches on the chains.
3¿
5¿ 3¿
(a) DNA double helix (b) Space-filling model The Monomers Are Monosaccharides
The repeating units of polysaccharides are simple sugars
Figure 3-19 The Structure of Double-Stranded DNA. (a) A
Chemistry
called monosaccharides (from the Greek mono, meaning
schematic representation of the double-helical structure of DNA. The
Review–
continuously turning strips represent the sugar-phosphate backbones “single,” and sakkharon, meaning “sugar”). A sugar can be de-
Nucleic
Acids: The of the molecule, and the horizontal bars represent paired bases of the fined as an aldehyde or ketone that has two or more hydroxyl
Double Helix groups. Thus, there are two categories of sugars: the aldo-
Activity: DNA two strands. (b) A space-filling model of the DNA double helix, with
Double Helix color-coded atoms as shown at the top of the figure. sugars, with a terminal carbonyl group (Figure 3-20a), and
the ketosugars, with an internal carbonyl group at carbon 2

helix is just sufficient to accommodate one of each kind of O

base. If we envision the sugar-phosphate backbones of the 1 1
H C CH2 OH
two strands as the sides of a circular staircase, then each step
2
or rung of the stairway corresponds to a pair of bases held in H
2
C OH C O
place by hydrogen bonding (Figure 3-19).
The right-handed Watson–Crick helix shown in Figure (H C OH) n-3 (H C OH) n-3
3-19 is actually an idealized version of what is called B-DNA. nCH nCH
OH
OH 2
B-DNA is the main form of DNA in cells, but two other forms 2

may also exist, perhaps in short segments interspersed within (a) Aldosugar (b) Ketosugar
molecules consisting mainly of B-DNA. A-DNA has a right- Figure 3-20 Structures of Monosaccharides. (a) Aldosugars
handed, helical configuration that is shorter and thicker than have a carbonyl group on carbon atom 1. (b) Ketosugars have a
B-DNA. Z-DNA, on the other hand, is a left-handed double he- carbonyl group on carbon atom 2. The number of carbon atoms in a
lix that derives its name from the zigzag pattern of its longer, monosaccharide (n) varies from three to seven.
86

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