3

I CHEMICAL BONDING,
MACROMOLECULES,
AND WATER 51
3.1 Strong and Weak Chemical Bonds 51
3.2 An Overview of Macromolecules
and Water as the Solvent of Life 52

II NONINFORMATIONAL
MACROMOLECULES 55
3.3 Polysaccharides 55
3.4 Lipids 56

Chemistry of Cellular III INFORMATIONAL

MACROMOLECULES 57
3.5 Nucleic Acids 57

Components 3.6 Amino Acids and the Peptide Bond

3.7 Proteins: Primary and Secondary
Structure 61
59

3.8 Proteins: Higher Order Structure and

Denaturation 62

All microbial cells, regardless of type, are composed of

macromoleculesproteins, nucleic acids, polysaccharides,
and lipids.

50
 Chapter 3 Chemistry of Cellular Components 51

UNIT 1
I CHEMICAL BONDING, H C C H
H H
H C C H
H C C H H C C H
H H
MACROMOLECULES,
AND WATER Ethylene, a double-bonded
organic compound
Acetylene, a triple-bonded
organic compound

A s we learned in the first two chapters, all cells have much

in common. The heart of microbial diversity lies in the
variations that cells display in the chemistry and arrangement
(a)

of their cellular components. These variations confer special
properties on each type of cell and allow the cell to carry out
specific functions.
To really understand how a cell works, it is necessary to
know the molecules that are present and the chemical processes
that take place. Molecules, especially macromolecules, are the
guts of the cell and are the subject of this chapter. It is assumed
that the reader has some background in elementary chemistry,
especially regarding the nature of atoms and atomic bonding.
Here we will expand on this background with a primer on rele-
vant biochemical bonds, followed by a discussion of the
structure and function of the four classes of macromolecules.
3.1 Strong and Weak Chemical Bonds
The major chemical elements in living things include hydro-
gen, oxygen, carbon, nitrogen, phosphorus, and sulfur
(l Section 5.1). These elements bond in various ways to
form the molecules of life. A molecule consists of two or more
atoms chemically bonded to one another. Thus, two oxygen
(O) atoms can combine to form a molecule of oxygen (O2).
Likewise, carbon (C), hydrogen (H), and O atoms can combine
to form glucose, C6H12O6, a hexose sugar (see Figure 3.4).
Covalent Bonds
In living things, chemical elements typically form strong
bonds in which electrons are shared more or less equally be-
tween atoms. These are called covalent bonds. To envision a
covalent bond, consider the formation of a molecule of water
from the elements O and H:
O + 2H HOH
Oxygen has six electrons in its outermost shell, and
hydrogen contains only a single electron. When O and 2H
combine to form H2O, covalent bonds maintain the three
atoms in tight association as a water molecule. In some
compounds, double and even triple covalent bonds can
form (Figure 3.1). The strength of these bonds increases
dramatically with their number. In cells single and double
covalent bonds are most common; triply bonded substances
are rare.
Chemical elements bond in different combinations to form
monomers, small molecules that in turn bond with each other to
form larger molecules called polymers. Covalently bonded poly-
mers in living things are called macromolecules. Thousands of
different monomers are known but only a relatively small num-
ber play important roles in the four classes of macromolecules.
To a large extent it is the chemical properties of monomers that
give macromolecules their distinctive structure and function.
O C O (CO2) N N (N2) O
O
P O- (PO43-)
O-
Carbon dioxide Nitrogen Phosphate
(b)
H O NH2 H H O
C C N C N C C C OH
H H NH2
N O
H
Peptide bond Cytosine (nitrogen Phenylalanine (amino
of proteins base of DNA and RNA) acid in proteins)
(c)
Figure 3.1 Covalent bonding of some molecules containing
double or triple bonds. (a) For acetylene and ethylene, both the
electronic configuration of the molecules and the conventional
shorthand for bonds is shown. (b) Some inorganic compounds with
double bonds. (c) Some organic compounds with double bonds.
Hydrogen Bonding and Polarity
In addition to covalent bonds, several weaker chemical bonds
also play an important role in biological molecules. Foremost
among these are hydrogen bonds. Hydrogen bonds form as
the result of weak electrostatic interactions between hydrogen
atoms and more electronegative (electron attracting) atoms,
such as oxygen or nitrogen (Figure 3.2). For example, because
an oxygen atom is electronegative but a hydrogen atom is not,
in the covalent bond between oxygen and hydrogen the
shared electrons orbit slightly nearer the oxygen nucleus than
the hydrogen nucleus. Because electrons carry a negative
charge, this creates a slight charge separation, oxygen slightly
negative and hydrogen slightly positive; this bridge is the
hydrogen bond. An individual hydrogen bond by itself is very
weak. However, when many hydrogen bonds form within and
between molecules, overall stability of the molecules can in-
crease dramatically.
Water is a polar substance. Because of this, water mole-
cules tend to associate with one another and remain apart
from nonpolar (hydrophobic) molecules. Water is extensively
hydrogen bonded. As water molecules orient themselves in so-
lution, the slight positive charge on a hydrogen atom can
bridge the negative charges on oxygen atoms (Figure 3.2a).
Hydrogen bonds also form between atoms in macromolecules
(Figure 3.2b,c). As these weak forces accumulate in a large
molecule such as a protein, they increase the stability of the
molecule and can also affect its overall structure. We will
see in Sections 3.5, 3.7, and 3.8 that hydrogen bonds play
major roles in the biological properties of proteins (Figure
3.2b) and nucleic acids (Figure 3.2c).
52 UNIT 1 Principles of Microbiology

H Amino terminus NH2 often control how different subunits in a multisubunit

H C R1 C R5 protein associate with one another (quaternary structure,

H
O () H () H Section 3.8) to form the biologically active molecule, and

O
C O H N
H(+) they also help stabilize RNA and cytoplasmic membranes.
H
(+) H N C O
()
H O

H
O (+) () H C R2 H C R4
H (+) O Bonding Patterns in Biological Molecules
(+) C O H N
(+) H H The element carbon is a major component of all macromole-
H

() (+)
O() H N C O
O
H O H cules. Carbon can bond not only with itself, but with many
H
(+)H
() H C R3 other elements as well, to yield large structures of consider-
able diversity and complexity. Different organic (carbon-
(a) Water (b) Amino acids in a protein
containing) compounds have different bonding patterns.
H Each of these patterns, called functional groups, has unique
N H O N chemical properties that are important in determining their
Guanine
biological role within the cell. An awareness of key functional
Cytosine N
N H N groups will make our later discussion of macromolecular
N H
N structure, cell physiology, and biosynthesis easier to follow.
H O H N Table 3.1 lists several functional groups of biochemical im-
H portance and examples of molecules or macromolecules that
H
contain them.
CH3 O H N N
Adenine 3.1 MiniReview
Thymine N H N N
N H Covalent bonds are strong bonds that bind elements in macro-
N
O molecules. Weak bonds, such as hydrogen bonds, van der Waals
H
Hydrogen forces, and hydrophobic interactions, also affect macromolecular
bonds structure, but they do so through more subtle atomic interac-
(c) Nitrogen bases in DNA tions. Various functional groups are common in biomolecules.

Figure 3.2 Hydrogen bonding in water and organic compounds. Why are covalent bonds stronger than hydrogen bonds?
Hydrogen bonds are shown as highlighted dotted lines. (b) Proteins. How can a hydrogen bond play a role in macromolecular
R represents the side chain of the amino acid (Figure 3.12). (c) Hydrogen structure?
bonds formed during complementary base pairing in DNA.

Other Weak Bonds 3.2 An Overview of Macromolecules

Weak interactions other than hydrogen bonds are also im-
portant in cells. For instance, van der Waals forces are weak
attractive forces that occur between atoms when they be-
come closer than about 34 angstroms (); van der Waals
forces can play significant roles in the binding of substrates
to enzymes (l Section 5.5) and in proteinnucleic acid
interactions.
Ionic bonds, such as that between Na and Cl- in NaCl,
are weak electrostatic interactions that support ionization in
aqueous solution. Many important biomolecules, such as car-
boxylic acids and phosphates (Table 3.1), are ionized at
cytoplasmic pH (typically pH 68) and thus can be dissolved
to high levels in the cytoplasm.
Hydrophobic interactions are also considered weak
bonds. Hydrophobic interactions occur when nonpolar
molecules or nonpolar regions of molecules associate
tightly in a polar environment. Hydrophobic interactions
can play major roles in controlling the folding of proteins
(Sections 3.7 and 3.8). Like van der Waals forces, hy-
drophobic interactions help bind substrates to enzymes
(l Section 5.5). In addition, hydrophobic interactions
and Water as the Solvent of Life
If you were to chemically analyze a cell of the common intes-
tinal bacterium Escherichia coli, what would you find? You
would find water as the major constituent, but after removing
the water, you would find large amounts of macromolecules,
much smaller amounts of monomers, and a variety of inor-
ganic ions (Table 3.2). About 95% of the dry weight of a cell
consists of macromolecules, and of these, proteins are by far
the most abundant class (Table 3.2).
Proteins are polymers of monomers called amino acids.
Proteins are found throughout the cell, playing both struc-
tural and enzymatic roles (Figure 3.3a). An average cell will
have over a thousand different types of proteins and multiple
copies of each (Table 3.2).
Nucleic acids are polymers of nucleotides and are found
in the cell in two forms, RNA and DNA. After proteins, ri-
bonucleic acids (RNAs) are the next most abundant
macromolecule in an actively growing cell (Table 3.2 and
Figure 3.3b). This is because there are thousands of ribosomes
(the machines that make new proteins) in each cell, and
 Chapter 3 Chemistry of Cellular Components 53

UNIT 1
Table 3.1 Some functional groups of biochemical importance

Functional group Structurea Biological relevance Example

O
Carboxylic acid C OH Organic, amino, and fatty acids; lipids; proteins Acetateb
O
Aldehyde C H Functional group of reducing sugars such as glucose; Formaldehyde
aldehydes
H
Alcohol C OH Lipids; carbohydrates Glucose
H

O
Keto C Citric acid cycle intermediates -ketoglutarate

O H
Ester C O C Triglycerides Lipids of Bacteria and
H Eukarya

O
Phosphate ester O P O C Nucleic acids DNA, RNA
O

O
Thioester C~S Energy metabolism; biosynthesis of fatty acids Acetyl-CoA

H H
Ether C O C Certain types of lipids Lipids of Archaea
H H

O O
Acid anhydride C~O P O Energy metabolism Acetyl phosphate
O

O O
Phosphoanhydride O P~O P O Energy metabolism Adenosine triphosphate
(ATP)
O O

O
Peptide R C C N C R Proteins Cellular proteins

a
A squiggle-type bond depiction (~) indicates an energy-rich bond (l Section 5.8).
b
Acetate (H3CCOO-) is the ionized form of acetic acid (H3CCOOH).

ribosomes are composed of a mixture of RNAs and protein. In
addition, smaller amounts of RNA are present in the form of
messenger and transfer RNAs, other key players in protein
synthesis. In contrast to RNA, DNA makes up a small fraction
of the bacterial cell (Table 3.2).
Lipids have both hydrophobic and hydrophilic properties
and play crucial roles in the cell as the backbone of mem-
branes and as storage depots for excess carbon (Figure 3.3d).
Polysaccharides are polymers of sugars and are present in
the cell, primarily in the cell wall. Like lipids, however, poly-
saccharides such as glycogen (discussed in the next section)
can be major forms of carbon and energy storage in the cell
(Figure 3.3c).
Water as a Biological Solvent
Macromolecules and all other molecules in cells are bathed in
water. Water has several important features that make it an
ideal biological solvent. Two key features are its polarity and
cohesiveness.
The polar properties of water are important because
many biologically important molecules (Table 3.2) are them-
selves polar and thus readily dissolve in water. As we will see
in Chapter 4, dissolved substances are continually passing
into and out of the cell through transport activities of the
cytoplasmic membrane (l Sections 4.3 and 4.4). These sub-
stances include nutrients needed to build new cell material
and waste products of metabolic processes.
54 UNIT 1 Principles of Microbiology

Cytoplasmic Cell wall

Table 3.2 Chemical composition of a prokaryotic cella Flagellum membrane Cytoplasm
Percent of Molecules per cell
Molecule dry weightb (different kinds)

Total macromolecules 96 24,610,000 (~2,500)

Protein 55 2,350,000 (~1,850)
Polysaccharide 5 4,300 (2)c
Lipid 9.1 22,000,000 (4)d (a) Proteins
Lipopolysaccharide 3.4 1,430,000 (1)
DNA 3.1 2.1 (1)
RNA 20.5 255,500 (~660) Nucleoid Ribosomes
e
Total monomers 3.0 (~350)
Amino acids and 0.5 (~100)
precursors
Sugars and precursors 2 (~50)
Nucleotides and 0.5 (~200)
precursors (b) Nucleic Acids: DNA RNA
Inorganic ions 1 (18)
Total 100%

a
Data from Neidhardt, F.C., et al. (eds.), 1996. Escherichia coli and Salmonella
typhimuriumCellular and Molecular Biology, 2nd edition. American Society for
Microbiology, Washington, DC.
b
Dry weight of an actively growing cell of E. coli 2.8 1013g; total weight
(70% water) 9.5 1013 g.
c
Assuming peptidoglycan and glycogen to be the major polysaccharides present. (c) Polysaccharides
d
There are several classes of phospholipids, each of which exists in many kinds Storage
because of variability in fatty acid composition between species and because of granules
different growth conditions.
e
Reliable estimates of monomer and inorganic ion composition are lacking.

The polar properties of water also promote the stability of

large molecules because of the increased opportunities for hy-
(d) Lipids
drogen bonding. Water forms three-dimensional networks,
both with itself (Figure 3.2a) and within macromolecules. By Figure 3.3 Macromolecules in the cell. (a) Proteins (brown) are
so doing, water molecules help to position atoms within bio- found throughout the cell both as parts of cell structures and as
molecules for potential interaction. The high polarity of water enzymes. The flagellum is a structure involved in swimming motility.
is also beneficial to the cell because it forces nonpolar sub- (b) Nucleic acids. DNA (green) is found in the nucleoid of prokaryotic
stances to aggregate and remain together. Membranes, for cells and in the nucleus of eukaryotic cells. RNA (orange) is found in the
example, contain large amounts of lipids, which have major cytoplasm (mRNA, tRNA) and in ribosomes (rRNA). (c) Polysaccharides
nonpolar (hydrophobic) components, and these aggregate in (yellow) are located in the cell wall and occasionally in internal storage
granules. (d) Lipids (blue) are found in the cytoplasmic membrane, the
such a way as to prevent the unrestricted flow of polar mole-
cell wall, and in storage granules.
cules into and out of the cell.
The polar nature of water makes it highly cohesive. This
means that water molecules have a high affinity for one an-
these important properties of water in mind, we now consider
other and form ordered arrangements in which hydrogen
the structure of the major macromolecules of life (Table 3.2
bonds (Figure 3.2a) are constantly forming, breaking, and
and Figure 3.3) in more detail.
re-forming. The cohesiveness of water is responsible for
some of its biologically important properties, such as high
surface tension and high specific heat (heat required to 3.2 MiniReview
raise the temperature 1C). Also, the fact that water expands
Proteins are the most abundant class of macromolecule in the
on freezing to yield a less dense solid form (ice) has a pro-
cell. Other macromolecules include the nucleic acids, lipids,
found effect on life in temperate and polar aquatic
and polysaccharides. Water is an excellent solvent for life
environments. In a lake, for example, ice on the surface in-
because of its polarity and cohesiveness.
sulates the water beneath the ice and prevents it from
freezing, thus allowing aquatic organisms to survive under Why do protein and RNA make up such a large proportion
the overlying ice. of an actively growing cell?
Life originated in water about 3.9 billion years ago Why does the high polarity of water make it useful as a
(l Figure 1.6), and virtually anywhere on Earth where liquid biological solvent?
water exists, microorganisms are likely to be found. With
 Chapter 3 Chemistry of Cellular Components 55

UNIT 1
II NONINFORMATIONAL Sugar Open Ring Significance
chain
MACROMOLECULES 1
Pentoses H C O 5
O
In this unit we examine the structure and function of nonin- 2 HOCH2 OH
H C OH Backbone
formational macromoleculespolysaccharides and lipids. 3 4C C1
H C OH H H of RNA
The sequence of monomers in these macromolecules does not Ribose 4 H C C2 H
H C OH 3
carry genetic information, but the macromolecules them- 5 OH OH
selves play important roles in the cell, primarily as structural CH2OH
or reserve materials.
1 5
Deoxyribose H C O O
HOCH2 OH
2
H C H
3.3 Polysaccharides 3 4
C
H H
C1 Backbone
of DNA
H C OH
Carbohydrates (sugars) are organic compounds that contain H
4 H
3C C2 H
C OH
carbon, hydrogen, and oxygen in a ratio of 1:2:1. The struc- 5 OH H
CH2OH
tural formula for glucose, the most abundant sugar on Earth is
C6H12O6 (Figure 3.4). The most biologically relevant carbohy- 1 6
Hexoses H C O HOCH2
drates are those containing four, five, six, and seven carbon 2 5 Energy
atoms (designated as C4, C5, C6, and C7). C5 sugars (pentoses) H C OH C O source;
Glucose 3
HO C H H OH cell walls
are of special significance because of their role as structural H
4 4C C1
backbones of nucleic acids. Likewise, C6 sugars (hexoses) are H C OH HO OH H H
5
the monomeric constituents of cell wall polymers and energy H C OH 3C C2
reserves. Figure 3.4 shows the structure of a few common 6
CH2OH H OH
sugars.
Derivatives of simple carbohydrates are common in cells. 1
Fructose CH2OH
When other chemical species replace one or more of the 2 6
C O O
hydroxyl groups on the sugar, derivatives are formed. For HOCH2 OH
3 Energy
example, the important bacterial cell wall polymer pepti- HO C H
4 5C H OH C2 source;
doglycan (l Section 4.6) contains the glucose derivative H C OH H C CH OH fruit sugar
5 3 C 1 2
N-acetylglucosamine (Figure 3.5). Besides sugar derivatives, H C OH
4

sugars having the same structural formula can differ in their 6 OH H

CH2OH
stereoisomeric properties. For example, a polysaccharide com-
posed of D-glucose differs from one containing L-glucose Figure 3.4 Structural formulas of a few common sugars. The
(Section 3.6). Hence, a large number of different sugars are formulas can be depicted in two alternate ways, open chain and ring.
The open chain is easier to visualize, but the ring form is the commonly
available to the cell for the construction of polysaccharides.
used structure. Note the numbering system on the ring. Glucose and
fructose are isomers of one another; they have the same molecular
The Glycosidic Bond composition but have different structures (Section 3.6).
Polysaccharides are carbohydrates containing many (some-
times hundreds or even thousands) of monomeric units called
monosaccharides. The latter are connected by covalent bonds Complex Polysaccharides
called glycosidic bonds (Figure 3.6). If two monosaccharides Polysaccharides can also combine with other classes of
are bonded by a glycosidic linkage, the resulting molecule is macromolecules, such as proteins and lipids, to form com-
a disaccharide. The addition of one more monosaccharide plex polysaccharidesglycoproteins and glycolipids. These
yields a trisaccharide, and several more an oligosaccharide. An
extremely long chain is then a polysaccharide.
Glycosidic bonds can form in two different geometric ori- Acetyl group 6
H 1 O CH2OH
entations, alpha () and beta () (Figure 3.6a). Polysaccharides
C H O 5
O
with a repeating structure composed of glucose units 2 H OH
H C N C CH3
bonded between carbons 1 and 4 in the alpha orientation 3 4 1
HO C H OH
(for example, glycogen and starch, Figure 3.6b) function as H
4 HO H
important carbon and energy reserves in bacteria, plants, H C OH 3 2
5
and animals. Glucose units joined by -1,4 linkages are pres- H C OH N replaces O H NH
6 in the sugar
ent in cellulose (Figure 3.6b), a stiff plant and algal cell wall CH2OH C O
component. Thus, even though both starch and cellulose CH3
contain only D-glucose, their functional properties differ
Open chain Ring structure
because of the different configurations, or , of their gly-
cosidic bonds. Figure 3.5 N-acetylglucosamine, a derivative of glucose. The O
on C-2 is replaced with an N- acetyl group.
56 UNIT 1 Principles of Microbiology

6 CH2OH 6 CH2OH
molecules. Polysaccharides can also contain other molecules
5 O 5 O such as protein or lipid, forming complex polysaccharides.
H H H H
H H
4 1 4 1 How can glycogen and cellulose differ so much in their physical
OH H OH H
HO 3 2 O 3 2 OH properties when they both consist of 100% D-glucose?

H OH H OH
-1,4-Glycosidic bond
3.4 Lipids
6
CH2 6 CH2OH
Lipids are essential components of cells and are amphipathic
O 5 O 5
H H H macromolecules, meaning that they show both hydrophilic
H H
1 O 4 1 O 4 and hydrophobic character. Lipid structure varies between
H OH H OH
2 3 2 H 3
the domains of life, and even within a domain many different
HO
lipids are known. Fatty acids are major constituents of
OH H OH H Bacteria and Eukarya lipids. By contrast, lipids of Archaea
-1,6-Glycosidic bond -1,4-Glycosidic bond contain a hydrocarbon (phytanyl) side chain not composed of
(a) fatty acids (l Section 4.3).
Fatty acids contain both hydrophobic and hydrophilic
components. Palmitate (the ionized form of palmitic acid),
is a common fatty acid in membrane lipids. Palmitate is a
16-carbon fatty acid composed of a chain of 15 saturated
Starch (fully hydrogenated and thus highly hydrophobic) carbon
-1,4 bonds
atoms and a single carboxylic acid group (the hydrophilic por-
tion) (Figure 3.7). Other common fatty acids in the lipids of
Bacteria include saturated or monounsaturated forms, from
-1,6 bonds C12 to C20 (Figure 3.7).

Triglycerides and Complex Lipids

Glycogen -1,4 bonds
Cellulose -1,4 bonds
(b)
Figure 3.6 The glycosidic bond and polysaccharides. (a) Structure
of different glycosidic bonds. Note that both the linkage (position on
the ring of the carbon atoms bonded) and the geometry ( or ) of the
linkage can vary about the glycosidic bond. (b) Structures of some
common polysaccharides. Compare color coding to (a).
compounds play important roles in cells, in particular as
cell-surface receptor molecules in cytoplasmic membranes.
The compounds typically reside on the external surfaces of
the membrane where they are in contact with the environ-
ment. Glycolipids constitute a major portion of the cell wall of
gram-negative bacteria and, as such, impart a number of
unique surface properties to these organisms (lSection 4.9).
3.3 MiniReview
Sugars can form long polymers called polysaccharides. The
two different orientations of the glycosidic bonds that link
sugar residues impart different properties to the resultant
Simple lipids (fats) consist of fatty acids (or phytanyl units in
Archaea) bonded to the C3 alcohol glycerol (Figure 3.7a, b).
Simple lipids are also called triglycerides because three fatty
acids are linked to the glycerol molecule. We will see when we
consider membrane structure (l Section 4.3) that the bond
between glycerol and the hydrophobic side chain is an ester
bond (Table 3.1) in cells of Bacteria and Eukarya but an ether
bond (Table 3.1) in Archaea.
Complex lipids are simple lipids that contain additional
elements such as phosphorus, nitrogen, or sulfur, or small hy-
drophilic organic compounds such as sugars (Figure 3.7d),
ethanolamine (Figure 3.7c), serine, or choline. Lipids contain-
ing a phosphate group, called phospholipids, are an important
class of complex lipids because they play a major structural
role in the cytoplasmic membrane (l Section 4.3).
The amphipathic property of lipids makes them ideal
structural components of membranes. Lipids aggregate to
form membranes; the hydrophilic (glycerol) portion is in con-
tact with the cytoplasm and the external environment
whereas the hydrophobic portion remains buried away inside
the membrane (l Section 4.3 and Figures 4.4 and 4.5).
Because of this property, membranes are ideal permeability
barriers. The inability of polar substances to flow through the
hydrophobic region of the lipids renders the membrane im-
permeable and prevents leakage of cytoplasmic constituents.
However, this also means that polar substances necessary for
cell function do not leak in, either, but we reserve this story for
the next chapter (transport, l Section 4.5)
 Chapter 3 Chemistry of Cellular Components 57

UNIT 1
Common fatty acids: O Simple lipids (triglycerides):
Fatty acids linked to glycerol by ester linkage Glycerol
16 15 14 13 12 11 10 9 8
7
6
5
4
3
2
1
C OH
H3C
O H
C16 saturated (palmitic)
C O C H
O H3C O
CH3 C OH C O C H
H3C O
C16 monounsaturated (palmitoleic) C O C H
H3C
H
Fatty acids Ester
linkage
(a) (b)

Complex lipid: Complex lipid:

Phosphatidyl ethanolamine (a phospholipid) Monogalactosyl diglyceride (a glycolipid)
O H 6
CH2OH
C O C H O
H3C 5
O OH
C O C H 4 1
H 3C O OH
Galactose 3 2
Fatty acids O P O C H
H
O H OH
Phosphate O C H
CH2 Fatty acids O
Ethanolamine C O C H
CH2 H3C O
+NH
3 C O C H
H3C
H
(c) (d)

Figure 3.7 Lipids. (a) Fatty acids differ in length, in position, and in number of double bonds. (b) Simple
lipids are formed by a dehydration reaction between fatty acids and glycerol to yield an ester linkage. The fatty
acid composition of a cell varies with growth temperature. (c, d) Complex lipids are simple lipids containing
other molecules.

3.4 MiniReview
Lipids contain both hydrophobic and hydrophilic components;
their chemical properties make them ideal structural compo-
nents for cytoplasmic membranes.
What part of a fatty acid molecule is hydrophobic? Hydrophilic?
How does a phospholipid differ from a triglyceride?
Draw the chemical structure of butyrate, a C4 fully saturated
fatty acid.
we already know, DNA carries the genetic blueprint for the
cell and RNA is the intermediary molecule that converts
the blueprint into defined amino acid sequences in proteins
(l Figure 1.4).
A nucleotide is composed of three components: a pentose
sugar, either ribose (in RNA) or deoxyribose (in DNA), a
nitrogen base, and a molecule of phosphate, PO43-. The gen-
eral structure of nucleotides of both DNA and RNA is very
similar (Figure 3.8).

O
III INFORMATIONAL Phosphate O P O
MACROMOLECULES O
5
CH2 O
The sequence of monomers in nucleic acids carries genetic in- Base
formation, and the sequence of monomers in proteins carries C 4 H H 1 C
structural and functional information. In contrast to polysac- H C
3 2
C H
charides and lipids, nucleic acids and proteins are thus
OH OH
informational macromolecules. Ribose
H only
in DNA
3.5 Nucleic Acids Figure 3.8 Nucleotides. The numbers on the sugar contain a prime
The nucleic acids deoxyribonucleic acid, DNA, and ribonucleic () after them because the ring structure in the nitrogen base is also
numbered (Figure 3.9).
acid, RNA, are macromolecules composed of monomers called
nucleotides. Therefore, DNA and RNA are polynucleotides. As
58 UNIT 1 Principles of Microbiology

Pyrimidine bases Purine bases nucleotides or nucleotide derivatives function in oxidation

reduction reactions in the cell (l Section 5.7) as carriers of
NH2 O O NH2 O sugars in the biosynthesis of polysaccharides (l Section
H3C N N
5 4 3N N N 7 5 6 1N N 5.15) and as regulatory molecules inhibiting or stimulating
8
2
6
1
2
O O O N
9 4
3
N
the activities of certain enzymes or metabolic events. How-
N N N N N NH2
H H H H H ever, we discuss here only the role of nucleotides as building
blocks of nucleic acids, the major informational function of
Cytosine Thymine Uracil Adenine Guanine nucleotides.
(C) (T) (U) (A) (G)

DNA DNA RNA DNA DNA Nucleic Acids

RNA only only
Figure 3.9 Structure of the nitrogen bases of DNA and RNA.
Note the numbering system of the rings. In attaching itself to the 1
carbon of the sugar phosphate shown in Figure 3.8, a pyrimidine base
bonds through N-1 and a purine base bonds at N-9.
Nucleotides
The nitrogen bases of nucleic acids belong to one of two chem-
ical classes. Purine basesadenine and guaninecontain two
fused heterocyclic rings (a heterocyclic ring contains more
than one kind of atom). Pyrimidine basesthymine, cytosine,
and uracilcontain a single six-membered heterocyclic ring
(Figure 3.9). Guanine, adenine, and cytosine are present in
both DNA and RNA. Thymine is present (with minor excep-
tions) only in DNA, and uracil is present only in RNA.
Nucleotides consist of a nitrogen base attached to a pen-
tose sugar by a glycosidic linkage between carbon atom 1 of
the sugar and a nitrogen atom of the base, either the nitrogen
atom labeled 1 (in a pyrimidine base) or 9 (in a purine base).
Without the phosphate, a nitrogen base bonded to its sugar is
called a nucleoside. Nucleotides are thus nucleosides contain-
ing one or more phosphates (Figure 3.10).
Nucleotides play other roles in the cell besides their major
role as components of nucleic acids. Nucleotides, especially
adenosine triphosphate (ATP) (Figure 3.10), are key forms of
chemical energy within the cell, releasing sufficient energy
during the hydrolysis of a phosphate bond to drive energy-
requiring reactions in the cell (l Section 5.8). Other
Phospho- Phosphate Ribose
anhydride ester
O O O 5 6 1N
O 2
O P ~ O P ~O P O CH
2 N
O O O
H H
Phosphates
OH
Figure 3.10 Components of the important nucleotide, adenosine
triphosphate. The energy of hydrolysis of a phosphoanhydride bond
(shown as squiggles) is greater than that of a phosphate ester bond,
which is significant in bioenergetics (l Section 5.8). With the
phosphate group removed, the molecule would be the nucleoside
adenosine.
RNA RNA The nucleic acid backbone is a polymer of alternating sugar
and phosphate molecules. Polynucleotides consist of nu-
cleotides covalently bonded via phosphate from carbon
3called the 3 (3 prime) carbonof one sugar to the 5 car-
bon of the adjacent sugar (Figure 3.11a). The phosphate
linkage is called a phosphodiester bond because a phos-
phate molecule connects two sugar molecules by ester linkage
(Figure 3.11a; Table 3.1).
The sequence of nucleotides in a DNA or RNA molecule is
called its primary structure. As we have discussed, the se-
quence of bases in a DNA or RNA molecule is informational,
encoding the sequence of amino acids in proteins or encoding
specific ribosomal or transfer RNAs. The replication of DNA
and the synthesis of RNA are key events in the life of a cell
(l Section 1.2 and Figure 1.4). We will see later that a virtu-
ally error-free mechanism is employed to ensure the faithful
transfer of genetic traits from one generation to another
(l Chapter 7).
DNA
In the genome of cells, DNA is double-stranded. Each chromo-
some consists of two strands of DNA, with each strand
containing hundreds of thousands to several million nu-
cleotides linked by phosphodiester bonds. The strands
associate with one another by hydrogen bonds that form
between the nitrogen bases in nucleotides of one strand and
the nitrogen bases in nucleotides of the other strand. When
positioned adjacent to one another, purine and pyrimidine
bases can undergo hydrogen bonding (see Figure 3.2c).
Hydrogen bonding is most stable when guanine (G)
bonds with cytosine (C) and adenine (A) bonds with thymine
(T) (see Figure 3.2c). Specific base pairing, A with T and G
with C, thus ensures that the two strands of DNA are
NH2 complementary in base sequence; that is, wherever a G is
N found in one strand, a C is found in the other, and wherever a
8
7 T is present in one strand, its complementary strand has an A
9 4
3 (Figure 3.11b).
N
Adenine
H H RNA
OH With a few exceptions, all RNAs are single-stranded molecules.
However, RNAs typically fold back upon themselves in re-
gions where complementary base pairing is possible to form
folded structures. This pattern of folding in RNA is called its
secondary structure (Figure 3.11c). In certain very large
RNA molecules, such as ribosomal RNA (l Sections 7.15
and 14.9), some parts of the molecule contain only primary
 Chapter 3 Chemistry of Cellular Components 59

UNIT 1
5 position
5 O 5 A G C T T A G C 3 Hydrogen bonds
H 2C Base Nitrogen base attached
to 1 position 3 T C G A A T C G 5
4 1
H H H
(b)
3 2 Deoxyribose
3 position O H
O P (i) 5 C A G U G A C C A U C G 3
O

Phosphodiester O
bond O
H2C Base (ii) 5 C C G A C A C G U C G G 3

H H H H A C Primary structure
C G
O H
A U Secondary
O P O Region of structure
complementary G C
O base pairing
C G
C G
5 3
(a) (c)

Figure 3.11 Nucleic acids: DNA and RNA. (a) Structure of part of a DNA chain. The nitrogen bases can be
adenine, guanine, cytosine, or thymine. In RNA, an OH group is present on the 2 carbon of the pentose sugar
(see Figure 3.8) and uracil replaces thymine. (b) Simplified structure of DNA in which only the nitrogen bases
are shown. The two strands are complementary in base sequence, with A joined to T by two hydrogen bonds
and G joined to C by three hydrogen bonds (note that the hydrogen bonds are indicated by two and three lines
rather than by dots as in Figure 3.2). (c) RNA: (i) a sequence showing only primary structure; (ii) a sequence that
allows for secondary structure. In RNA, secondary structures form when opportunities for intrastrand base pairing
arise, as shown here.

structure but others contain both primary and secondary
structure. This leads to highly folded and twisted molecules
whose biological function is critically dependent on their final
three-dimensional shape.
At least four classes of RNA exist in cells. Messenger RNA
(mRNA) carries the genetic information of DNA in a single-
stranded molecule complementary in base sequence to that of
DNA. Transfer RNAs (tRNAs) convert the genetic information
present in mRNA into the language of amino acids, the build-
ing blocks of proteins. Ribosomal RNAs (rRNAs), of which
there are several types, are important structural and catalytic
components of the ribosome, the protein-synthesizing system
of the cell. In addition to these, a variety of small RNAs exist
in cells. These RNAs function to regulate the production or ac-
tivity of other RNAs. These various types of RNA are
discussed in detail in Chapters 7, 9, and 11.
3.5 MiniReview
The informational content of a nucleic acid is determined by the
sequence of nitrogen bases along the polynucleotide chain.
Both RNA and DNA are informational macromolecules. RNA can
fold into various configurations to obtain secondary structure.
What components are found in a nucleotide?
How does a nucleoside differ from a nucleotide?
Distinguish between the primary and secondary structure
of RNA.
3.6 Amino Acids and the Peptide Bond
Amino acids are the monomers of proteins. Most amino
acids consist of carbon, hydrogen, oxygen, and nitrogen only,
but 2 of the 22 genetically encoded amino acids also contain
sulfur, and 1 contains selenium. All amino acids contain two im-
portant functional groups, a carboxylic acid group (COOH)
and an amino group (NH2) (Table 3.1 and Figure 3.12a).
These groups are key to the structure of proteins because co-
valent bonds can form between the carboxyl carbon of one
amino acid and the amino nitrogen of a second amino acid
(with elimination of a molecule of water) to form the peptide
bond (Figure 3.13).
Structure of Amino Acids
All amino acids have the general structure shown in Fig-
ure 3.12a. But each type of amino acid is unique because of its
unique side group (abbreviated R in Figure 3.12a) attached to
the -carbon. The -carbon is the carbon atom adjacent to the
carboxylic acid group. The side chains vary considerably in
structure, from as simple as a hydrogen atom in the amino
acid glycine to aromatic rings in phenylalanine, tyrosine, and
tryptophan (Figure 3.12b).
The chemical properties of an amino acid are governed by
its side chain. Amino acids that have similar chemical proper-
ties are grouped into related amino acid families as shown
in Figure 3.12b. For example, the side chain may contain a
carboxylic acid group, such as in aspartic acid or glutamic
60 UNIT 1 Principles of Microbiology

O H Gly Glycine (G)

-carbon H O
-O C CH
2 Asp Aspartate (D)
H 2N C C OH O CH3 Ala Alanine (A)
R Carboxylic -O C CH CH Glu Glutamate (E)
Amino group acid group 2 2 CH3
CH Val Valine (V)
+NH CH CH CH CH Lys Lysine (K) CH3
(a)General structure of an amino acid 3 2 2 2 2 CH3
O CH CH2 Leu Leucine (L)
H H CH3
H3C C C C N (CH2)4 Pyl Pyrrolysine (O) CH3
OH CH2 Ser Serine (S) H2 C N CH Ile Isoleucine (I)
CH3 CH2
C
CH3 CH Thr Threonine (T) H2 CH3 S CH2 CH2 Met Methionine(M)
O OH +NH C H N CH2 CH2 CH2 Arg Arginine (R)
2
NH2 C CH2 Asn Asparagine (N) CH2 Phe Phenylalanine (F)
NH2
O +HN CH2 His Histidine (H)
NH2 C CH2 CH2 Gln Glutamine (Q) CH2 Trp Tryptophan(W)
N
H N
HS CH2 Cys Cysteine (C) H
Key H2C CH2
HSe CH2 Sec Selenocysteine (U) Ionizable: acidic Pro Proline (P)
H2C CH COO
Ionizable: basic N
H
HO CH2 Tyr Tyrosine (Y) Nonionizable polar
Nonpolar (Note: Because proline lacks a free amino group,
(hydrophobic) the entire structure of this amino acid is shown,
(b)Structure of the amino acid R groups
not just the R group.

Figure 3.12 Structure of the 22 genetically encoded amino acids. (a) General structure. (b) R group
structure. The three-letter codes for the amino acids are to the left of the names, and the one-letter codes are
in parentheses to the right of the names. Pyrrolysine has thus far been found only in certain methanogenic
Archaea (l Sections 2.10 and 17.4).

acid, rendering the amino acid acidic. Others contain addi- The diversity of chemically distinct amino acids makes
tional amino groups, rendering them basic. Alternatively, possible an enormous number of unique proteins with widely
several amino acids contain hydrophobic side chains and are different biochemical properties. For example, if one assumes
grouped together as nonpolar amino acids. The amino acid that an average polypeptide contains 100 amino acids, there
cysteine contains a sulfhydryl group (SH). Sulfhydryl groups are 22100 different polypeptide sequences that are theoretically
can connect one chain of amino acids to another by disulfide possible. No cell has anywhere near this many different pro-
linkage (RSSR) through two cysteine molecules, one teins. However, a cell of Escherichia coli contains almost
from each chain. 2,000 different kinds of proteins (Table 3.2). These include
different soluble and membrane-integrated enzymes, struc-
tural proteins, transport proteins, sensory proteins, and many
others.
H O H O
H
H2N C C OH + H N C C OH Isomers
R1 R2 Two molecules may have the same molecular formula but ex-
ist in different structural forms. These related but
nonidentical molecules are called isomers. For example, the
H2O
hexose sugars glucose and fructose (Figure 3.4) are isomers.
Louis Pasteur, the famous early microbiologist who quashed
N-terminus C-terminus
H O H H O the theory of spontaneous generation (l Section 1.7), began
H2N C C N C C OH his scientific career as a chemist studying a class of isomers
R1 R2 called optical isomers. Optical isomers that have the same
molecular and structural formulas, except that one is a
Peptide mirror image of the other (just as the left hand is a mirror
bond
image of the right), are called enantiomers. The enantiomers
Figure 3.13 Peptide bond formation. R1 and R2 refer to the of a given compound can never be superimposed one over the
variable portions (side chains) of the amino acids (Figure 3.12). Note other and are designated as either D or L (Figure 3.14),
how, following peptide bond formation, a free OH group is present at depending on whether a pure solution rotates light to the right
the C-terminus for formation of the next peptide bond.
 Chapter 3 Chemistry of Cellular Components 61

UNIT 1
or left, respectively. Sugars of the D enantiomer predominate a a
in biological systems.
Amino acids also have D or L enantiomers. However, in
proteins cells employ the L-amino acid rather than the D form
(Figure 3.14c). Nevertheless, D-amino acids are occasionally d C b b C d
found in cells, most notably in the cell wall polymer peptido-
glycan (l Section 4.6) and in certain peptide antibiotics
(l Section 27.9). Cells can interconvert certain enantiomers
c c
by the activity of enzymes called racemases. For instance,
some prokaryotes can grow on L-sugars or D-amino acids (a)
because they have racemases that can convert these forms
into the opposite enantiomer before metabolizing them.
D-Glucose L-Glucose L-Alanine D-Alanine

H O H O COOH COOH
3.6 MiniReview C C
H2N C H H C NH2
Twenty-two different amino acids are found in cells and can H C OH HO C H CH3 CH3
bond to each other via the peptide bond. Mirror image HO C H H C OH
(enantiomeric) forms of sugars and amino acids exist, but only H C OH HO C H COOH COOH
one optical isomer of each is found in most cell polysaccharides H C OH HO C H C C
and proteins. H2N H H NH2
CH2OH CH2OH CH3 CH3
Why can it be said that all amino acids are structurally
Three-dimensional projection
similar yet different simultaneously?
(b) (c)
Draw the complete structure of a dipeptide containing the
amino acids alanine and tyrosine. Outline the peptide bond. Figure 3.14 Isomers. (a) Ball-and-stick model showing mirror images.
(b) Enantiomers of glucose. (c) Enantiomers of the amino acid alanine.
Which enantiomeric forms of sugars and amino acids are In the three-dimensional projection the arrow should be understood as
commonly found in living organisms? Why doesnt the coming toward the viewer and the dashed line indicates a plane away
amino acid glycine have different enantiomers? (Hint: Look from the viewer. Note that no matter how the three-dimensional views
carefully at Figure 3.14c and replace the alanine shown with are rotated, the L and D forms can never be superimposed. This is a
glycine.) characteristic of enantiomers.

A protein consists of one or more polypeptides. The num-

3.7 Proteins: Primary and
Secondary Structure
Proteins play several key roles in cell function. In essence, a
cell is what it is and does what it does because of the kinds
and amounts of proteins it contains; that is, every different
type of cell has a different complement of proteins. An un-
derstanding of protein structure is therefore essential for
understanding how cells work.
Two major classes of proteins are catalytic proteins
(enzymes) and structural proteins. Enzymes are the
catalysts for chemical reactions that occur in cells (lChap-
ters 5, 20, and 21). By contrast, structural proteins are
integral parts of the major structures of the cell: membranes,
walls, cytoplasmic components, and so on. However, all
proteins show certain basic features in common, and we
discuss these now.
Primary Structure
As we have said, proteins are polymers of amino acids cova-
lently bonded by peptide bonds (Figure 3.13). Two amino acids
bonded by peptide linkage constitute a dipeptide, three amino
acids, a tripeptide, and so on. When many amino acids are co-
valently linked via peptide bonds, they form a polypeptide.
ber of amino acids differs greatly from one protein to another;
proteins containing as few as 15 or as many as 10,000 amino
acids are known. Because proteins differ in their composition,
sequence, and number of amino acids, it is obvious that enor-
mous variation in protein structure (and thus function) is
possible.
The linear array of amino acids in a polypeptide is called
its primary structure. The primary structure of a polypeptide
is critical to its final function because it is consistent with only
certain types of folding patterns. And it is only the final, folded
polypeptide that assumes biological activity. The two ends
of a polypeptide are so designated by whether a free car-
boxylic acid group or a free amino group exists; the terms
C-terminus and N-terminus are used to describe these two
ends, respectively (Figure 3.2b).
Secondary Structure
Once formed, a polypeptide does not remain a linear struc-
ture. Instead it folds to form a more stable structure.
Interactions of the R groups on the amino acids in a poly-
peptide force the molecule to twist and fold in a specific way.
This forms the secondary structure. Hydrogen bonds, the
weak noncovalent linkages discussed earlier (Section 3.1),
62 UNIT 1 Principles of Microbiology

R C R C R C
O O
O C O H N C O
O C N
C C
H H N C O H N
C CH N CH
CH N C R C R C R
CH N R H R
R O C N H O C
R H
H N H O C N H
O
O R C R C R C
C C O
C C O H N
CH N
H
C N H N C O H N
R H Hydrogen bonds
R between nearby C R C R C R
H
O amino acids O C N H O C
O
C N H O C N H
C H R C R C R C
CH N C
N R C O H N C O
R
H H N C O H N
H
O C R C R C R
O O C N H O C
C
C N
CH
CH N
H
H R Hydrogen bonds
R between distant
amino acids
(a) -helix ( b) -sheet

Figure 3.15 Secondary structure of polypeptides. (a) -helix secondary structure.

(b) -sheet secondary structure. Note that the hydrogen bonding is between atoms in the
peptide bonds and does not involve the R groups.

play important roles in polypeptide secondary structure. One
common type of secondary structure is the -helix. To envi-
sion an -helix, imagine a linear polypeptide wound around
a cylinder (Figure 3.15a). In this twisted structure, oxygen
and nitrogen atoms from different amino acids become
positioned close enough to allow hydrogen bonding. These
hydrogen bonds give the -helix its inherent stability (Fig-
ure 3.15a).
The primary structure of some polypeptides induces a dif-
ferent type of secondary structure, called a -sheet. In the
-sheet, the chain of amino acids in the polypeptide folds back
and forth upon itself instead of forming a helix. However, as in
the -helix, the folding in a -sheet exposes hydrogen atoms
that can undergo hydrogen bonding (Figure 3.15b). Typically,
a -sheet secondary structure yields a polypeptide that is
rather rigid and -helical secondary structures are more flexi-
ble. Thus, an enzyme, for example, whose activity may
depend on its being rather flexible, may contain a high degree
of -helix secondary structure. By contrast, a structural pro-
tein that functions in cellular scaffolding may contain large
regions of -sheet secondary structure.
Many polypeptides contain regions of both -helix and
-sheet secondary structure, the type of folding and its loca-
tion in the molecule being determined by the primary
structure and the available opportunities for hydrogen bond-
ing and hydrophobic interactions (see Figure 3.16). A typical
protein is thus made up of many domains, as they are called,
regions of the protein that have a specific structure and func-
tion in the final, biologically active, molecule.
3.8 Proteins: Higher Order Structure
and Denaturation
Once a polypeptide has achieved secondary structure it con-
tinues to fold to form an even more stable molecule. This
folding results in a unique three-dimensional shape called the
tertiary structure of the protein.
Like secondary structure, tertiary structure is ultimately
determined by primary structure. However, tertiary structure
is also governed to some extent by the secondary structure of
the molecule because the side chain of each amino acid in the
polypeptide is positioned in a specific way (Figure 3.15). If
additional hydrogen bonds, covalent bonds, hydrophobic in-
teractions, or other atomic interactions are able to form, the
polypeptide will fold to accommodate them (Figure 3.16).
The tertiary folds of the polypeptide ultimately form ex-
posed regions or grooves in the molecule (Figure 3.16 and see
Figure 3.17) that are important for binding other molecules
(for example, in the binding of a substrate to an enzyme or the
binding of DNA to a specific regulatory protein) (l Sections
5.5 and 9.2).
Frequently a polypeptide folds in such a way that adjacent
sulfhydryl groups of cysteine residues are exposed. These free
SH groups can form a disulfide bond between the two
amino acids. If the two cysteine residues are located in dif-
ferent polypeptides in a protein, the disulfide bond covalently
links the two molecules (Figure 3.16a). In addition, a single
polypeptide chain can fold and bond to itself if a disulfide
bond can form within the molecule.
 Chapter 3 Chemistry of Cellular Components 63

UNIT 1
Chains Chains
A chain
-helix
SS

SS

B chain
S
S

-sheet

(a) Insulin (b) Ribonuclease Chains Chains

(a) (b)
Figure 3.16 Tertiary structure of polypeptides. (a) Insulin, a pro-
tein containing two polypeptide chains; note how the B chain contains Figure 3.17 Quaternary structure of human hemoglobin.
both -helix and -sheet secondary structure and how disulfide link- (a) There are two kinds of polypeptide in human hemoglobin, chains
ages (SS) help in dictating folding patterns (tertiary structure). (shown in blue and red) and chains (shown in orange and yellow), but
(b) Ribonuclease, a large protein with several regions of -helix and a total of four polypeptides in the final protein molecule (two chains
-sheet secondary structure. and two chains). Separate colors are used to distinguish each chain.
(b) Molecular structure of human hemoglobin as determined by X-ray
crystallography. In this view each chain is red and each chain is blue.
Quaternary Structure
If a protein consists of two or more polypeptides, and many
proteins do, the number and type of polypeptides that form
the final protein molecule are referred to as its quaternary
structure (Figure 3.17). In proteins showing quaternary
structure, each polypeptide, called a subunit, contains pri-
mary, secondary, and tertiary structure. Some proteins contain
multiple copies of a single subunit. A protein containing two
identical subunits, for example, would be called a homodimer.
Other proteins may contain nonidentical subunits, each
Gentle Active Harsh
present in one or more copies (a heterodimer, for example, denaturation; denaturation;
protein
contains one copy each of two different polypeptides). The urea 100C
subunits in multisubunit proteins are held together by nonco-
valent interactions (hydrogen bonding, van der Waals forces,
and hydrophobic interactions) or by covalent linkages, typi-
cally disulfide bonds.

Denaturation
When proteins are exposed to extremes of heat or pH or to
certain chemicals or metals that affect their folding, they may
undergo denaturation (Figure 3.18). Denaturation causes Inactive Inactive
the polypeptide chain to unfold, destroying the higher order
Remove urea;
(secondary, tertiary, and quaternary, if relevant) structure of Cool
reactivation
the molecule. Depending on the severity of the denaturant or
denaturing conditions, the polypeptide may refold after the
denaturant is removed (Figure 3.18). Typically, however, de-
natured proteins unfold such that their hydrophobic regions
become exposed and stick together to form protein aggregates
that lack biological activity.
The biological properties of a protein are usually lost
when it is denatured. Peptide bonds (Figure 3.13) are un-
affected, however, and so a denatured molecule retains its Active
protein Inactive
primary structure. This shows that biological activity is not
inherent in the primary structure of a protein but instead is a Figure 3.18 Denaturation of the protein ribonuclease. Ribonuclease
function of the uniquely folded form of the molecule as ulti- structure was shown in Figure 3.16b. Note how harsh denaturation
mately directed by primary structure. In other words, folding permanently destroys a molecule (from the standpoint of biological
function) because of improper folding but primary structure is retained.
64 UNIT 1 Principles of Microbiology

of a polypeptide confers upon it a unique shape that is com-
patible with a specific biological function.
Denaturation of proteins is a major means of destroying
microorganisms. For example, alcohols such as phenol and
ethanol are effective disinfectants because they readily pene-
trate cells and irreversibly denature their proteins. Such
chemical agents are thus useful for disinfecting inanimate
objects such as surfaces and have enormous practical value in
household, hospital, and industrial disinfectant applications.
We discuss disinfectants, along with other chemical and phys-
ical agents used to destroy microorganisms, in Chapter 27.
Moving On
Now that we have reviewed the chemistry of cellular compo-
nents, we are in a better position to understand the structural
details of cells. In the next chapter we will see how macro-
molecules come together to form major structures of the cell,
such as the cytoplasmic membrane, the cell wall, and the flagel-
lum. From there we will consider the basic metabolic properties
of cells in Chapter 5. Metabolism, the machine function of a cell,
drives the biosynthesis and assembly of new copies of macro-
molecules; these processes result in cell growth (lChapter 6).
The metabolic events themselves are directed by the coding
functions of the cell, the essential genetic events carried out by
all cells. We discuss molecular biology in Chapters 79.
As the contemporary microbiologist Norman Pace has
put it, life is fundamentally chemistry. And as any micro-
biologist will attest, a feeling for the biochemistry of proteins,
lipids, nucleic acids, and polysaccharides is essential to a
grasp of modern microbiology and will accelerate the under-
standing of both basic and more advanced principles.
3.7 and 3.8 MiniReview
The primary structure of a protein is determined by its amino
acid sequence, but the folding (higher order structure) of the
polypeptide determines how the protein functions in the cell.
Define the terms primary, secondary, and tertiary with
respect to protein structure.
How does a polypeptide differ from a protein?
What secondary structural features tend to make -sheet
proteins more rigid than -helices?
Describe the number and kinds of polypeptides present in a
homotetrameric protein.
Describe the structural and biological effects of the denatu-
ration of a protein. Of what practical value is knowledge of
protein denaturation?

Review of Key Terms

Amino acid one of the 22 different monomers
that make up proteins; chemically, a two-
carbon carboxylic acid containing an amino
group and a characteristic substituent on the
alpha carbon
Covalent bond a chemical bond in which
electrons are shared between two atoms
Denaturation destruction of the folding prop-
erties of a protein leading (usually) to protein
aggregation and loss of biological activity
Domain in the context of proteins, a portion
of the protein typically possessing a specific
structure or function
DNA (deoxyribonucleic acid) a polymer of de-
oxyribonucleotides linked by phosphodiester
bonds that carries genetic information
Enantiomer a form of a molecule that is the
mirror image of another form of the same
molecule
Enzyme a protein or an RNA that catalyzes a
specific chemical reaction in a cell
Fatty acid an organic acid containing a car-
boxylic acid group and a hydrocarbon chain
of various lengths; major components of
lipids of Bacteria and Eukarya
Glycosidic bond a covalent bond linking
sugars together in a polysaccharide
Hydrogen bond a weak chemical interaction
between a hydrogen atom and a second,
more electronegative element, usually an
oxygen or nitrogen atom
Isomers two molecules with the same
molecular formula but a difference in
structure
Lipid a polar compound such as glycerol
bonded to fatty acids or other hydrophobic
molecules by ester or ether linkage, often
also containing other groups, such as phos-
phate or sugars
Macromolecule a polymer of covalently
linked monomeric units, such as DNA, RNA,
polysaccharides, and lipids
Molecule two or more atoms chemically
bonded to one another
Monomer a small molecule that is a building
block for larger molecules
Nonpolar possessing hydrophobic (water-
repelling) characteristics and not easily
dissolved in water
Nucleic acid DNA or RNA
Nucleotide a monomer of a nucleic acid con-
taining a nitrogen base (adenine, guanine,
cytosine, thymine, or uracil), one or more
molecules of phosphate, and a sugar, either
ribose (in RNA) or deoxyribose (in DNA)
Peptide bond a type of covalent bond linking
amino acids in a polypeptide
Phosphodiester bond a type of covalent
bond linking nucleotides together in a
polynucleotide
Polar possessing hydrophilic (water-loving)
characteristics and generally water soluble
Polymer a large molecule made up of
monomers
Polynucleotide a polymer of nucleotides
bonded to one another by covalent bonds
called phosphodiester bonds
Polypeptide a polymer of amino acids
bonded to one another by peptide bonds
 Chapter 3 Chemistry of Cellular Components 65

Polysaccharide a polymer of sugar units
bonded to one another by glycosidic bonds
Primary structure in an informational
macromolecule such as a polypeptide or a
nucleic acid, the precise sequence of
monomeric units
Protein a polypeptide or group of
polypeptides forming a molecule of specific
biological function
Purine one of the nitrogen bases of nucleic
acids that contain two fused rings; adenine
and guanine
UNIT 1
Pyrimidine one of the nitrogen bases of usually dictated by opportunities for hydro-
nucleic acids that contain a single ring; cyto- gen bonding
sine, thymine, and uracil Tertiary structure the final folded structure
Quaternary structure in proteins, the num- of a polypeptide that has previously attained
ber and types of individual polypeptides in secondary structure
the final protein molecule
RNA (ribonucleic acid) a polymer of ribonu-
cleotides linked by phosphodiester bonds
that plays many roles in cells, in particular,
during protein synthesis
Secondary structure the initial pattern of
folding of a polypeptide or a polynucleotide,

Review Questions

1. Which are the major elements found in living organisms? Why
are oxygen and hydrogen particularly abundant in living organ-
isms (Section 3.1)?
2. Define the word molecule. How many atoms are in a mole-
cule of hydrogen gas? How many atoms are in a molecule of
glucose (Sections 3.1 and 3.3)?
3. Refer to the structure of the nitrogen base cytosine shown in
Figure 3.1. Draw this structure and then label the positions of
all single bonds and double bonds in the cytosine molecule
(Section 3.1).
4. Compare and contrast the words monomer and polymer.
Give three examples of biologically important polymers and
list the monomers of which they are composed. Which classes
of macromolecules are most abundant (by weight) in a cell
(Sections 3.1 and 3.2)?
5. List the components that would make up a simple lipid. How
does a triglyceride differ from a complex lipid (Section 3.4)?
6. Examine the structures of the triglyceride and of phosphatidyl
ethanolamine shown in Figure 3.7. How might the substitution
of phosphate and ethanolamine for a fatty acid alter the chemi-
cal properties of the lipid (Section 3.4)?
7. RNA and DNA are similar types of macromolecules but show
distinct differences as well. List three ways in which RNA
differs chemically or physically from DNA. What is the cellular
function of DNA and RNA (Section 3.5)?
8. Why are amino acids so named? Write a general structure for
an amino acid. What is the importance of the R group to final
protein structure? Why does the amino acid cysteine have spe-
cial significance for protein structure (Section 3.6)?
9. What type of reaction between two amino acids leads to forma-
tion of the peptide bond (Section 3.6)?
10. Define the types of protein structure: primary, secondary, terti-
ary, and quaternary. Which of these structures are altered by
denaturation (Sections 3.7 and 3.8)?
11. Fill in the blanks. A glycosidic bond is to a ___________ as a
___________ bond is to a polypeptide and a ___________ is to a
nucleic acid. All of these bonds are examples of ___________
bonds, which are chemically much stronger than weak bonds,
such as ___________, ___________, and ___________

Application Questions

1. Observe the following nucleotide sequences of RNA:
(a) GUCAAAGAC, (b) ACGAUAACC. Can either of these RNA
molecules have secondary structure? If so, draw the potential
secondary structure(s).
2. A few soluble (cytoplasmic) proteins contain a high content of
hydrophobic amino acids. How would you predict these pro-
teins would fold into their tertiary structure and why?
3. Cells of the genus Halobacterium, an organism that lives in very
salty environments, contain over 5 molar (M) potassium (K).
Because of this high K content, many cytoplasmic proteins of
Halobacterium cells are enriched in two specific amino acids
that are present in much higher proportions in Halobacterium
proteins than in functionally similar proteins from Escherichia
coli (which has only very low levels of K in its cytoplasm).
Which amino acids are enriched in Halobacterium proteins and
why? (Hint: Which amino acids could best neutralize the posi-
tive charges due to K?)
4. When a culture of the bacterium Escherichia coli, an inhabitant
of the human gut, is placed in a beaker of boiling water, signifi-
cant changes in the cells occur almost immediately. However,
when a culture of Pyrodictium, a hypothermophile that grows
optimally in boiling hot springs is put in the same beaker, similar
changes do not occur. Explain.
5. Review Figure 3.6b and then describe the differences that make
each of these polymers unique. If all of the glycosidic bonds in
these polymers were hydrolyzed, what single molecule would
remain?
6. Review Figure 3.12b. Of all the amino acids shaded in blue,
what is it about their chemistry that unites them as a family?