Old Version Chapter 3- Chemistry of Cellular Components

Chemistry of CellularComponents

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

III INFORMATIONAL

MACROMOLECULES 57

3.5 Nucleic Acids 57

3.6 Amino Acids and the Peptide Bond 59

3.7 Proteins: Primary and SecondaryStructure 61

3.8 Proteins: Higher Order Structure andDenaturation 62

3

All microbial cells, regardless of type, are composed of

macromolecules—proteins, nucleic acids, polysaccharides,

and lipids.

50

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Hydrogen Bonding and PolarityIn addition to covalent bonds, several weaker chemical bondsalso play an important role in biological molecules. Foremostamong these are hydrogen bonds. Hydrogen bonds form asthe result of weak electrostatic interactions between hydrogenatoms and more electronegative (electron attracting) atoms,such as oxygen or nitrogen (Figure 3.2). For example, becausean oxygen atom is electronegative but a hydrogen atom is not,in the covalent bond between oxygen and hydrogen theshared electrons orbit slightly nearer the oxygen nucleus thanthe hydrogen nucleus. Because electrons carry a negativecharge, this creates a slight charge separation, oxygen slightlynegative and hydrogen slightly positive; this bridge is thehydrogen bond. An individual hydrogen bond by itself is veryweak. However, when many hydrogen bonds form within andbetween 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 apartfrom nonpolar (hydrophobic) molecules. Water is extensivelyhydrogen bonded. As water molecules orient themselves in so-lution, the slight positive charge on a hydrogen atom canbridge 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 largemolecule such as a protein, they increase the stability of themolecule and can also affect its overall structure. We willsee in Sections 3.5, 3.7, and 3.8 that hydrogen bonds playmajor roles in the biological properties of proteins (Figure3.2b) and nucleic acids (Figure 3.2c).

I CHEMICAL BONDING,MACROMOLECULES, AND WATER

As we learned in the first two chapters, all cells have muchin common. The heart of microbial diversity lies in the

variations that cells display in the chemistry and arrangementof their cellular components. These variations confer specialproperties on each type of cell and allow the cell to carry outspecific functions.

To really understand how a cell works, it is necessary toknow the molecules that are present and the chemical processesthat take place. Molecules, especially macromolecules, are the“guts” of the cell and are the subject of this chapter. It is assumedthat 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 thestructure 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(lSection 5.1). These elements bond in various ways toform the molecules of life. A molecule consists of two or moreatoms 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 combineto form glucose, C6H12O6, a hexose sugar (see Figure 3.4).

Covalent BondsIn living things, chemical elements typically form strongbonds in which electrons are shared more or less equally be-tween atoms. These are called covalent bonds. To envision acovalent bond, consider the formation of a molecule of waterfrom the elements O and H:

Oxygen has six electrons in its outermost shell, andhydrogen contains only a single electron. When O and 2Hcombine to form H2O, covalent bonds maintain the threeatoms in tight association as a water molecule. In somecompounds, double and even triple covalent bonds canform (Figure 3.1). The strength of these bonds increasesdramatically with their number. In cells single and doublecovalent bonds are most common; triply bonded substancesare rare.

Chemical elements bond in different combinations to formmonomers, small molecules that in turn bond with each other toform larger molecules called polymers. Covalently bonded poly-mers in living things are called macromolecules. Thousands ofdifferent 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 thatgive macromolecules their distinctive structure and function.

O O+ 2H H H

51Chapter 3 ❚ Chemistry of Cellular Components

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OH

NH2

Peptide bondof proteins

Cytosine (nitrogenbase of DNA and RNA)

Phenylalanine (aminoacid in proteins)

(CO2) (PO43-)

Carbon dioxide

(N2)

Nitrogen

–O

O-

O-P

Phosphate

Ethylene, a double-bonded organic compound

Acetylene, a triple-bonded organic compound

H

H

H

H

H H

O O

O

O

O

HH H

H H

H H

HC C C CHHHH C C C C

C

C C C C C C

N N

N

O

N

N

NH2

(a)

(b)

(c)

Figure 3.1 Covalent bonding of some molecules containingdouble or triple bonds. (a) For acetylene and ethylene, both theelectronic configuration of the molecules and the conventionalshorthand for bonds is shown. (b) Some inorganic compounds withdouble bonds. (c) Some organic compounds with double bonds.

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Other Weak BondsWeak interactions other than hydrogen bonds are also im-portant in cells. For instance, van der Waals forces are weakattractive forces that occur between atoms when they be-come closer than about 3–4 angstroms (Å); van der Waalsforces can play significant roles in the binding of substratesto enzymes (lSection 5.5) and in protein–nucleic acidinteractions.

Ionic bonds, such as that between Na� and Cl- in NaCl,are weak electrostatic interactions that support ionization inaqueous solution. Many important biomolecules, such as car-boxylic acids and phosphates (Table 3.1), are ionized atcytoplasmic pH (typically pH 6–8) and thus can be dissolvedto high levels in the cytoplasm.

Hydrophobic interactions are also considered weakbonds. Hydrophobic interactions occur when nonpolarmolecules or nonpolar regions of molecules associatetightly in a polar environment. Hydrophobic interactionscan 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(lSection 5.5). In addition, hydrophobic interactions

often control how different subunits in a multisubunitprotein associate with one another (quaternary structure,Section 3.8) to form the biologically active molecule, andthey also help stabilize RNA and cytoplasmic membranes.

Bonding Patterns in Biological MoleculesThe element carbon is a major component of all macromole-cules. Carbon can bond not only with itself, but with manyother elements as well, to yield large structures of consider-able diversity and complexity. Different organic (carbon-containing) compounds have different bonding patterns.Each of these patterns, called functional groups, has uniquechemical properties that are important in determining theirbiological role within the cell. An awareness of key functionalgroups will make our later discussion of macromolecularstructure, cell physiology, and biosynthesis easier to follow.Table 3.1 lists several functional groups of biochemical im-portance and examples of molecules or macromolecules thatcontain them.

3.1 MiniReview

Covalent bonds are strong bonds that bind elements in macro-molecules. Weak bonds, such as hydrogen bonds, van der Waalsforces, and hydrophobic interactions, also affect macromolecularstructure, but they do so through more subtle atomic interac-tions. Various functional groups are common in biomolecules.

❚ Why are covalent bonds stronger than hydrogen bonds?

❚ How can a hydrogen bond play a role in macromolecularstructure?

3.2 An Overview of Macromoleculesand 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? Youwould find water as the major constituent, but after removingthe 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 cellconsists of macromolecules, and of these, proteins are by farthe 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 willhave over a thousand different types of proteins and multiplecopies of each (Table 3.2).

Nucleic acids are polymers of nucleotides and are foundin the cell in two forms, RNA and DNA. After proteins, ri-bonucleic acids (RNAs) are the next most abundantmacromolecule in an actively growing cell (Table 3.2 andFigure 3.3b). This is because there are thousands of ribosomes(the “machines” that make new proteins) in each cell, and

UNIT 1 ❚ Principles of Microbiology52

Figure 3.2 Hydrogen bonding in water and organic compounds.Hydrogen bonds are shown as highlighted dotted lines. (b) Proteins. R represents the side chain of the amino acid (Figure 3.12). (c) Hydrogenbonds formed during complementary base pairing in DNA.

NN

N

N

N

N

N

H

H

H

H

H

O

O

CH3

Hydrogen bonds

(a) Water (b) Amino acids in a protein

(c) Nitrogen bases in DNA

N

N

N

NH

H O

N

OH

H

H

N

NH

H

Cytosine

N

C

C

N

C

C

O

O

H

H

H

O

O

H

C

N

C

C

N

C

H

OH

H

H

HH

H

H

H

Guanine

Adenine

Thymine

H

H

H

H

H

H

H H

H

O

O

O

O

O

O HO

R1

CH R3

R2

R5

NH2

R4

N

Amino terminus

(–)

(–)(–)

(–)

(–)(–)

(+)

(+)

(+)

(+)

(+)

(+)

(+)

(+)

(–)

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ribosomes are composed of a mixture of RNAs and protein. Inaddition, smaller amounts of RNA are present in the form ofmessenger and transfer RNAs, other key players in proteinsynthesis. In contrast to RNA, DNA makes up a small fractionof the bacterial cell (Table 3.2).

Lipids have both hydrophobic and hydrophilic propertiesand 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 inthe 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 SolventMacromolecules and all other molecules in cells are bathed inwater. Water has several important features that make it anideal biological solvent. Two key features are its polarity andcohesiveness.

The polar properties of water are important becausemany biologically important molecules (Table 3.2) are them-selves polar and thus readily dissolve in water. As we will seein Chapter 4, dissolved substances are continually passinginto and out of the cell through transport activities of thecytoplasmic membrane (lSections 4.3 and 4.4). These sub-stances include nutrients needed to build new cell materialand waste products of metabolic processes.

Table 3.1 Some functional groups of biochemical importance

Functional group Structurea Biological relevance Example

Carboxylic acid C

O

OH Organic, amino, and fatty acids; lipids; proteins Acetateb

Aldehyde C

O

H Functional group of reducing sugars such as glucose;aldehydes

Formaldehyde

Alcohol C

H

H

OH Lipids; carbohydrates Glucose

Keto C

O

Citric acid cycle intermediates �-ketoglutarate

Ester C

H

H

OC

O

Triglycerides Lipids of Bacteria andEukarya

Phosphate ester C

O

O–

O–O P Nucleic acids DNA, RNA

Thioester C~S

O

Energy metabolism; biosynthesis of fatty acids Acetyl-CoA

Ether C

H

H

C

H

H

O Certain types of lipids Lipids of Archaea

Acid anhydride C~O

O O–

O–OP Energy metabolism Acetyl phosphate

Phosphoanhydride P~O

O– O–

OO

O––O P Energy metabolism Adenosine triphosphate(ATP)

Peptide C C

O

N RCR Proteins Cellular proteins

aA squiggle-type bond depiction (~) indicates an “energy-rich” bond (lSection 5.8).bAcetate (H3CCOO-) is the ionized form of acetic acid (H3CCOOH).

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these important properties of water in mind, we now considerthe structure of the major macromolecules of life (Table 3.2and Figure 3.3) in more detail.

3.2 MiniReview

Proteins are the most abundant class of macromolecule in thecell. Other macromolecules include the nucleic acids, lipids,and polysaccharides. Water is an excellent solvent for lifebecause of its polarity and cohesiveness.

❚ Why do protein and RNA make up such a large proportionof an actively growing cell?

❚ Why does the high polarity of water make it useful as abiological solvent?

The polar properties of water also promote the stability oflarge molecules because of the increased opportunities for hy-drogen bonding. Water forms three-dimensional networks,both with itself (Figure 3.2a) and within macromolecules. Byso doing, water molecules help to position atoms within bio-molecules for potential interaction. The high polarity of wateris also beneficial to the cell because it forces nonpolar sub-stances to aggregate and remain together. Membranes, forexample, contain large amounts of lipids, which have majornonpolar (hydrophobic) components, and these aggregate insuch a way as to prevent the unrestricted flow of polar mole-cules into and out of the cell.

The polar nature of water makes it highly cohesive. Thismeans that water molecules have a high affinity for one an-other and form ordered arrangements in which hydrogenbonds (Figure 3.2a) are constantly forming, breaking, andre-forming. The cohesiveness of water is responsible forsome of its biologically important properties, such as highsurface tension and high specific heat (heat required toraise the temperature 1°C). Also, the fact that water expandson freezing to yield a less dense solid form (ice) has a pro-found effect on life in temperate and polar aquaticenvironments. In a lake, for example, ice on the surface in-sulates the water beneath the ice and prevents it fromfreezing, thus allowing aquatic organisms to survive underthe overlying ice.

Life originated in water about 3.9 billion years ago(lFigure 1.6), and virtually anywhere on Earth where liquidwater exists, microorganisms are likely to be found. With


Figure 3.3 Macromolecules in the cell. (a) Proteins (brown) arefound throughout the cell both as parts of cell structures and asenzymes. The flagellum is a structure involved in swimming motility. (b) Nucleic acids. DNA (green) is found in the nucleoid of prokaryoticcells and in the nucleus of eukaryotic cells. RNA (orange) is found in thecytoplasm (mRNA, tRNA) and in ribosomes (rRNA). (c) Polysaccharides(yellow) are located in the cell wall and occasionally in internal storagegranules. (d) Lipids (blue) are found in the cytoplasmic membrane, thecell wall, and in storage granules.

(a) Proteins

(b) Nucleic Acids:

(c) Polysaccharides

(d) Lipids

Storage granules

FlagellumCytoplasmicmembrane

Cell wallCytoplasm

RibosomesNucleoid

DNA RNA

Table 3.2 Chemical composition of a prokaryotic cella

MoleculePercent of dry weightb

Molecules per cell (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

Lipopolysaccharide 3.4 1,430,000 (1)DNA 3.1 2.1 (1)RNA 20.5 255,500 (~660)

Total monomers 3.0 —e(~350)Amino acids and

precursors0.5 —(~100)

Sugars and precursors 2 —(~50)Nucleotides and

precursors0.5 —(~200)

Inorganic ions 1 —(18)Total 100% —

aData from Neidhardt, F.C., et al. (eds.), 1996. Escherichia coli and Salmonellatyphimurium—Cellular and Molecular Biology, 2nd edition. American Society forMicrobiology, Washington, DC.bDry weight of an actively growing cell of E. coli � 2.8 � 10�13g; total weight (70% water) � 9.5 � 10�13 g.cAssuming peptidoglycan and glycogen to be the major polysaccharides present.dThere are several classes of phospholipids, each of which exists in many kindsbecause of variability in fatty acid composition between species and because ofdifferent growth conditions.eReliable estimates of monomer and inorganic ion composition are lacking.

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II NONINFORMATIONALMACROMOLECULES

In this unit we examine the structure and function of nonin-formational macromolecules—polysaccharides and lipids.The sequence of monomers in these macromolecules does notcarry genetic information, but the macromolecules them-selves play important roles in the cell, primarily as structuralor reserve materials.

3.3 Polysaccharides

Carbohydrates (sugars) are organic compounds that containcarbon, hydrogen, and oxygen in a ratio of 1:2:1. The struc-tural formula for glucose, the most abundant sugar on Earth isC6H12O6 (Figure 3.4). The most biologically relevant carbohy-drates are those containing four, five, six, and seven carbonatoms (designated as C4, C5, C6, and C7). C5 sugars (pentoses)are of special significance because of their role as structuralbackbones of nucleic acids. Likewise, C6 sugars (hexoses) arethe monomeric constituents of cell wall polymers and energyreserves. Figure 3.4 shows the structure of a few commonsugars.

Derivatives of simple carbohydrates are common in cells.When other chemical species replace one or more of thehydroxyl groups on the sugar, derivatives are formed. Forexample, the important bacterial cell wall polymer pepti-doglycan (l Section 4.6) contains the glucose derivativeN-acetylglucosamine (Figure 3.5). Besides sugar derivatives,sugars having the same structural formula can differ in theirstereoisomeric properties. For example, a polysaccharide com-posed of D-glucose differs from one containing L-glucose(Section 3.6). Hence, a large number of different sugars areavailable to the cell for the construction of polysaccharides.

The Glycosidic BondPolysaccharides are carbohydrates containing many (some-times hundreds or even thousands) of monomeric units calledmonosaccharides. The latter are connected by covalent bondscalled glycosidic bonds (Figure 3.6). If two monosaccharidesare bonded by a glycosidic linkage, the resulting molecule isa disaccharide. The addition of one more monosaccharideyields a trisaccharide, and several more an oligosaccharide. Anextremely long chain is then a polysaccharide.

Glycosidic bonds can form in two different geometric ori-entations, alpha (α) and beta (β) (Figure 3.6a). Polysaccharideswith a repeating structure composed of glucose unitsbonded between carbons 1 and 4 in the alpha orientation(for example, glycogen and starch, Figure 3.6b) function asimportant carbon and energy reserves in bacteria, plants,and animals. Glucose units joined by β-1,4 linkages are pres-ent in cellulose (Figure 3.6b), a stiff plant and algal cell wallcomponent. Thus, even though both starch and cellulosecontain only D-glucose, their functional properties differbecause of the different configurations, α or β, of their gly-cosidic bonds.


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1

23

4

5

Sugar Open

chain

Ring Significance

Backbone of RNA

Ribose

Pentoses

Backbone of DNA

Deoxyribose

Energy source;cell walls

Glucose

Hexoses

Energy source;fruit sugar

Fructose

H

H

H

H

HH H

H

H

H H

H

H

HH

H

HH

H

H

H

H

H HH

H

H

H

H

H

H

H

HH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OH

OHOH

OH

C

C

C

C

C

C C

C

C

C

C

C

C

C

C

C

C

C

C C

C

C

C C

C

C

C

C C

C

C

C

C

C

OO

O

O

O O

OO

CH2OH

HOCH2

HOCH2

HOCH2

HOCH2

CH2OH

CH2OH

CH2OH

CH2OH

CH2OH

HO

HO

HO

1

23

4

51

2

3

4

5

1

2

3

4

5

1

2

3

4

5

6

1

2

3

4

5

6

1

23

4

5

6

5

6

4 3

2

1

HC

O

CH N

H

C

O

CH3

C HHO

C OHH

C OHH

CH2OH

N replaces Oin the sugar

Acetyl group

Ring structureOpen chain

CH2OH

O

HHOH

H

HO

H NH

C O

CH3

OH2

1

3

4

5

6

1

23

4

5

6

Figure 3.4 Structural formulas of a few common sugars. Theformulas can be depicted in two alternate ways, open chain and ring.The open chain is easier to visualize, but the ring form is the commonlyused structure. Note the numbering system on the ring. Glucose andfructose are isomers of one another; they have the same molecularcomposition but have different structures (Section 3.6).

Figure 3.5 N-acetylglucosamine, a derivative of glucose. The Oon C-2 is replaced with an N-acetyl group.

Complex PolysaccharidesPolysaccharides can also combine with other classes ofmacromolecules, such as proteins and lipids, to form com-plex polysaccharides—glycoproteins and glycolipids. These

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compounds play important roles in cells, in particular as cell-surface receptor molecules in cytoplasmic membranes.The compounds typically reside on the external surfaces ofthe membrane where they are in contact with the environ-ment. Glycolipids constitute a major portion of the cell wall ofgram-negative bacteria and, as such, impart a number ofunique surface properties to these organisms (lSection 4.9).

3.3 MiniReview

Sugars can form long polymers called polysaccharides. Thetwo different orientations of the glycosidic bonds that linksugar residues impart different properties to the resultant

molecules. Polysaccharides can also contain other moleculessuch as protein or lipid, forming complex polysaccharides.

❚ How can glycogen and cellulose differ so much in their physicalproperties when they both consist of 100% D-glucose?

3.4 Lipids

Lipids are essential components of cells and are amphipathicmacromolecules, meaning that they show both hydrophilicand hydrophobic character. Lipid structure varies betweenthe domains of life, and even within a domain many differentlipids are known. Fatty acids are major constituents ofBacteria and Eukarya lipids. By contrast, lipids of Archaeacontain a hydrocarbon (phytanyl) side chain not composed offatty acids (lSection 4.3).

Fatty acids contain both hydrophobic and hydrophiliccomponents. Palmitate (the ionized form of palmitic acid),is a common fatty acid in membrane lipids. Palmitate is a16-carbon fatty acid composed of a chain of 15 saturated(fully hydrogenated and thus highly hydrophobic) carbonatoms and a single carboxylic acid group (the hydrophilic por-tion) (Figure 3.7). Other common fatty acids in the lipids ofBacteria include saturated or monounsaturated forms, fromC12 to C20 (Figure 3.7).

Triglycerides and Complex LipidsSimple lipids (fats) consist of fatty acids (or phytanyl units inArchaea) bonded to the C3 alcohol glycerol (Figure 3.7a, b).Simple lipids are also called triglycerides because three fattyacids are linked to the glycerol molecule. We will see when weconsider membrane structure (lSection 4.3) that the bondbetween glycerol and the hydrophobic side chain is an esterbond (Table 3.1) in cells of Bacteria and Eukarya but an etherbond (Table 3.1) in Archaea.

Complex lipids are simple lipids that contain additionalelements 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 importantclass of complex lipids because they play a major structuralrole in the cytoplasmic membrane (lSection 4.3).

The amphipathic property of lipids makes them idealstructural components of membranes. Lipids aggregate toform membranes; the hydrophilic (glycerol) portion is in con-tact with the cytoplasm and the external environmentwhereas the hydrophobic portion remains buried away insidethe membrane (lSection 4.3 and Figures 4.4 and 4.5).Because of this property, membranes are ideal permeabilitybarriers. The inability of polar substances to flow through thehydrophobic region of the lipids renders the membrane im-permeable and prevents leakage of cytoplasmic constituents.However, this also means that polar substances necessary forcell function do not leak in, either, but we reserve this story forthe next chapter (transport, lSection 4.5)


α-1,4 bonds

α-1,6 bonds

β-1,4 bonds

α-1,4 bonds

1

23

4

5

1

23

4

5

3

4

5

3

4

5

6

1

2

1

2

6

66

O

CH2OH

H

H

OH

OH

H

H

HO

H

O

CH2OH

H

OHH

OH

OH

H

HH

O

Starch

Glycogen

Cellulose

(b)

(a)

OH

H

OH

CH2

OH

H

HH

O

HO

O

HH

OH

CH2OH

OH

H

HH

O

α-1,4-Glycosidic bond

α-1,6-Glycosidic bond β-1,4-Glycosidic bond

Figure 3.6 The glycosidic bond and polysaccharides. (a) Structureof different glycosidic bonds. Note that both the linkage (position onthe ring of the carbon atoms bonded) and the geometry (� or �) of thelinkage can vary about the glycosidic bond. (b) Structures of somecommon polysaccharides. Compare color coding to (a).

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we already know, DNA carries the genetic blueprint for thecell 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 pentosesugar, either ribose (in RNA) or deoxyribose (in DNA), anitrogen base, and a molecule of phosphate, PO4

3-. The gen-eral structure of nucleotides of both DNA and RNA is verysimilar (Figure 3.8).

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 saturatedfatty acid.

III INFORMATIONALMACROMOLECULES

The sequence of monomers in nucleic acids carries genetic in-formation, and the sequence of monomers in proteins carriesstructural and functional information. In contrast to polysac-charides and lipids, nucleic acids and proteins are thusinformational macromolecules.

3.5 Nucleic Acids

The nucleic acids deoxyribonucleic acid, DNA, and ribonucleicacid, RNA, are macromolecules composed of monomers callednucleotides. Therefore, DNA and RNA are polynucleotides. As


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H3CC O

O

H3CC O

OC

C

H

H

H

P O

O

C H

H

–O

O

CH2

CH2+NH3

Ethanolamine

Phosphate

Fatty acids

Complex lipid:Phosphatidyl ethanolamine (a phospholipid)

H3CC16 saturated (palmitic)

C16 monounsaturated (palmitoleic)

C OH

O

CH3 C OH

O

Common fatty acids:

12

3546

78

910

1112

1314

1516

OH

OH

OH

H3CC O

O

H3CC O

OC

C

H

H

H

O C H

H

O

CH2OH

Galactose

Fatty acids

Complex lipid:

Monogalactosyl diglyceride (a glycolipid)

23

4

5

6

1

H3CC O

O

C H

H3CC O

O

C H

H3CC O

O

C H

H

HEster linkage

Simple lipids (triglycerides):

Fatty acids linked to glycerol by ester linkage Glycerol

Fatty acids

(a) (b)

(c) (d)

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

P

O

O–

O–O

C C

O Base

OH

H HHH C

OHRibose

Phosphate

5′

4′3′ 2′

1′

C

CH2

H onlyin DNA

Figure 3.8 Nucleotides. The numbers on the sugar contain a prime(�) after them because the ring structure in the nitrogen base is alsonumbered (Figure 3.9).

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NucleotidesThe nitrogen bases of nucleic acids belong to one of two chem-ical classes. Purine bases—adenine and guanine—contain twofused heterocyclic rings (a heterocyclic ring contains morethan one kind of atom). Pyrimidine bases—thymine, cytosine,and uracil—contain a single six-membered heterocyclic ring(Figure 3.9). Guanine, adenine, and cytosine are present inboth 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 ofthe sugar and a nitrogen atom of the base, either the nitrogenatom labeled 1 (in a pyrimidine base) or 9 (in a purine base).Without the phosphate, a nitrogen base bonded to its sugar iscalled a nucleoside. Nucleotides are thus nucleosides contain-ing one or more phosphates (Figure 3.10).

Nucleotides play other roles in the cell besides their majorrole as components of nucleic acids. Nucleotides, especiallyadenosine triphosphate (ATP) (Figure 3.10), are key forms ofchemical energy within the cell, releasing sufficient energyduring the hydrolysis of a phosphate bond to drive energy-requiring reactions in the cell (lSection 5.8). Other

nucleotides or nucleotide derivatives function in oxidation–reduction reactions in the cell (lSection 5.7) as carriers ofsugars in the biosynthesis of polysaccharides (lSection5.15) and as regulatory molecules inhibiting or stimulatingthe activities of certain enzymes or metabolic events. How-ever, we discuss here only the role of nucleotides as buildingblocks of nucleic acids, the major informational function ofnucleotides.

Nucleic AcidsThe nucleic acid backbone is a polymer of alternating sugarand phosphate molecules. Polynucleotides consist of nu-cleotides covalently bonded via phosphate from carbon3—called the 3� (3 prime) carbon—of one sugar to the 5� car-bon of the adjacent sugar (Figure 3.11a). The phosphatelinkage 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 iscalled 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 encodingspecific ribosomal or transfer RNAs. The replication of DNAand the synthesis of RNA are key events in the life of a cell(lSection 1.2 and Figure 1.4). We will see later that a virtu-ally error-free mechanism is employed to ensure the faithfultransfer of genetic traits from one generation to another(lChapter 7).

DNAIn the genome of cells, DNA is double-stranded. Each chromo-some consists of two strands of DNA, with each strandcontaining hundreds of thousands to several million nu-cleotides linked by phosphodiester bonds. The strandsassociate with one another by hydrogen bonds that formbetween the nitrogen bases in nucleotides of one strand andthe nitrogen bases in nucleotides of the other strand. Whenpositioned adjacent to one another, purine and pyrimidinebases 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 Gwith C, thus ensures that the two strands of DNA arecomplementary in base sequence; that is, wherever a G isfound in one strand, a C is found in the other, and wherever aT is present in one strand, its complementary strand has an A(Figure 3.11b).

RNAWith 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 formfolded structures. This pattern of folding in RNA is called itssecondary structure (Figure 3.11c). In certain very largeRNA molecules, such as ribosomal RNA (lSections 7.15and 14.9), some parts of the molecule contain only primary

Cytosine

(C)

DNA

RNA

NH

O

NH2

N

Thymine

(T)

DNA

only

N

NH

O

O

H3C

Uracil

(U)

RNA

only

N

NH

O

O

DNA

RNA

Guanine

(G)

N

N

N

NH

NH2

O

DNA

RNA

N

N

65

4 321

Pyrimidine bases Purine bases

Adenine

(A)

N

N

NH2

H

5

67

98

1 2

43

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 basebonds through N-1 and a purine base bonds at N-9.

Phosphate ester

Ribose

H

OCH2

OHOH

N N

NN

NH2

OPOPOP–O

O

O–

O

O–

O

O–

Phospho- anhydride

H H H

~ ~65

4 32

178

9

Adenine

Phosphates

Figure 3.10 Components of the important nucleotide, adenosinetriphosphate. 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 (lSection 5.8). With thephosphate group removed, the molecule would be the nucleosideadenosine.

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3.6 Amino Acids and the Peptide Bond

Amino acids are the monomers of proteins. Most aminoacids consist of carbon, hydrogen, oxygen, and nitrogen only,but 2 of the 22 genetically encoded amino acids also containsulfur, 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 oneamino acid and the amino nitrogen of a second amino acid(with elimination of a molecule of water) to form the peptidebond (Figure 3.13).

Structure of Amino AcidsAll amino acids have the general structure shown in Fig-ure 3.12a. But each type of amino acid is unique because of itsunique side group (abbreviated R in Figure 3.12a) attached tothe α-carbon. The α-carbon is the carbon atom adjacent to thecarboxylic acid group. The side chains vary considerably instructure, from as simple as a hydrogen atom in the aminoacid glycine to aromatic rings in phenylalanine, tyrosine, andtryptophan (Figure 3.12b).

The chemical properties of an amino acid are governed byits side chain. Amino acids that have similar chemical proper-ties are grouped into related amino acid “families” as shownin Figure 3.12b. For example, the side chain may contain acarboxylic acid group, such as in aspartic acid or glutamic

structure but others contain both primary and secondarystructure. This leads to highly folded and twisted moleculeswhose biological function is critically dependent on their finalthree-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 ofDNA. Transfer RNAs (tRNAs) convert the genetic informationpresent in mRNA into the language of amino acids, the build-ing blocks of proteins. Ribosomal RNAs (rRNAs), of whichthere are several types, are important structural and catalyticcomponents of the ribosome, the protein-synthesizing systemof the cell. In addition to these, a variety of small RNAs existin cells. These RNAs function to regulate the production or ac-tivity of other RNAs. These various types of RNA arediscussed in detail in Chapters 7, 9, and 11.

3.5 MiniReview

The informational content of a nucleic acid is determined by thesequence of nitrogen bases along the polynucleotide chain.Both RNA and DNA are informational macromolecules. RNA canfold 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.

H H

H2C BaseO

O3′

1′

2′

5′

5′

5′

5′ 3′

3′

3′

3′

3′ 5′

P O–O

H H H

H

H

H2C BaseO

O

O

(i)

(ii)

5′ position

P O–O

O

Nitrogen base attached to 1′ position

Deoxyribose

Phosphodiesterbond

Primary structure

Secondary

structureRegion of complementary base pairing

3′ position

(a)

(b)

A

C G

G C

C G

C G

A U

(c)

A GG CC T T A

T CC GG A A T

C C A U C GA CG U G A

C C U C G GC GG A C A

C

5′

4′

H

H

Hydrogen bonds

Figure 3.11 Nucleic acids: DNA and RNA. (a) Structure of part of a DNA chain. The nitrogen bases can beadenine, 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 basesare shown. The two strands are complementary in base sequence, with A joined to T by two hydrogen bondsand G joined to C by three hydrogen bonds (note that the hydrogen bonds are indicated by two and three linesrather than by dots as in Figure 3.2). (c) RNA: (i) a sequence showing only primary structure; (ii) a sequence thatallows for secondary structure. In RNA, secondary structures form when opportunities for intrastrand base pairingarise, as shown here.

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acid, rendering the amino acid acidic. Others contain addi-tional amino groups, rendering them basic. Alternatively,several amino acids contain hydrophobic side chains and aregrouped together as nonpolar amino acids. The amino acidcysteine contains a sulfhydryl group (—SH). Sulfhydryl groupscan connect one chain of amino acids to another by disulfidelinkage (R—S—S—R) through two cysteine molecules, onefrom each chain.

The diversity of chemically distinct amino acids makespossible an enormous number of unique proteins with widelydifferent biochemical properties. For example, if one assumesthat an average polypeptide contains 100 amino acids, thereare 22100 different polypeptide sequences that are theoreticallypossible. No cell has anywhere near this many different pro-teins. However, a cell of Escherichia coli contains almost2,000 different kinds of proteins (Table 3.2). These includedifferent soluble and membrane-integrated enzymes, struc-tural proteins, transport proteins, sensory proteins, and manyothers.

IsomersTwo molecules may have the same molecular formula but ex-ist in different structural forms. These related butnonidentical molecules are called isomers. For example, thehexose sugars glucose and fructose (Figure 3.4) are isomers.Louis Pasteur, the famous early microbiologist who quashedthe theory of spontaneous generation (lSection 1.7), beganhis scientific career as a chemist studying a class of isomerscalled optical isomers. Optical isomers that have the samemolecular and structural formulas, except that one is a“mirror image” of the other (just as the left hand is a mirrorimage of the right), are called enantiomers. The enantiomersof a given compound can never be superimposed one over theother and are designated as either D or L (Figure 3.14),depending on whether a pure solution rotates light to the right

CH2OH Ser Serine (S)

CHCH3

OH

Thr Threonine (T)

CH2C

O

NH2 Asn Asparagine (N)

CH2C

O

CH2NH2 Gln Glutamine (Q)

CH2HS Cys Cysteine (C)

CH2HO Tyr Tyrosine (Y)

CH2HSe Sec Selenocysteine(U)

H Gly Glycine (G)

N

CH2H2C

H2C CH COO–Pro Proline (P)

H

CHCH3

CH3

Val Valine (V)

CH2CHCH3

CH3

Leu Leucine (L)

CHCH3

CH2CH3

Ile Isoleucine (I)

CH2 Phe Phenylalanine (F)

CH2

NH

Trp Tryptophan(W)

CH3 Ala Alanine (A)

CH2C

O

C

O

-O CH2 Glu Glutamate (E)

CH2

O-O Asp Aspartate (D)C

(CH2)4

CH2 CH2CH2CH2+NH3 Lys Lysine (K)

CH2CH2CH2

H3C

H2CC

+NH2 NH

N

N

HH

C

CC

NH2

Arg Arginine (R)

Pyl Pyrrolysine (O)

CH2

HN

+HN His Histidine (H)

Met Methionine(M)CH2S CH2CH3

OHC

O

C

R

H

H2N

Amino group Carboxylic acid group

α-carbon

Ionizable: acidic

Ionizable: basic

Nonionizable polar

Nonpolar(hydrophobic)

Key

(a)—General structure of an amino acid

(b)—Structure of the amino acid “R” groups

(Note: Because proline lacks a free amino group,the entire structure of this amino acid is shown, not just the R group.

H2

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

H2N C C

H O

OH NH

C C

H

R2

O

OH+ H

H2O

H2N C C

H

R1

O

N C C

H

R2

O

OH

Peptide

bond

R1

HN-terminus C-terminus

Figure 3.13 Peptide bond formation. R1 and R2 refer to thevariable portions (side chains) of the amino acids (Figure 3.12). Notehow, following peptide bond formation, a free OH group is present atthe C-terminus for formation of the next peptide bond.

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A protein consists of one or more polypeptides. The num-ber of amino acids differs greatly from one protein to another;proteins containing as few as 15 or as many as 10,000 aminoacids 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) ispossible.

The linear array of amino acids in a polypeptide is calledits primary structure. The primary structure of a polypeptideis critical to its final function because it is consistent with onlycertain types of folding patterns. And it is only the final, foldedpolypeptide that assumes biological activity. The two endsof 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 twoends, respectively (Figure 3.2b).

Secondary StructureOnce 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, theweak noncovalent linkages discussed earlier (Section 3.1),

or left, respectively. Sugars of the D enantiomer predominatein biological systems.

Amino acids also have D or L enantiomers. However, inproteins cells employ the L-amino acid rather than the D form(Figure 3.14c). Nevertheless, D-amino acids are occasionallyfound in cells, most notably in the cell wall polymer peptido-glycan (lSection 4.6) and in certain peptide antibiotics(lSection 27.9). Cells can interconvert certain enantiomersby the activity of enzymes called racemases. For instance,some prokaryotes can grow on L-sugars or D-amino acidsbecause they have racemases that can convert these formsinto the opposite enantiomer before metabolizing them.

3.6 MiniReview

Twenty-two different amino acids are found in cells and canbond to each other via the peptide bond. Mirror image(enantiomeric) forms of sugars and amino acids exist, but onlyone optical isomer of each is found in most cell polysaccharidesand proteins.

❚ Why can it be said that all amino acids are structurallysimilar yet different simultaneously?

❚ Draw the complete structure of a dipeptide containing theamino acids alanine and tyrosine. Outline the peptide bond.

❚ Which enantiomeric forms of sugars and amino acids arecommonly found in living organisms? Why doesn’t theamino acid glycine have different enantiomers? (Hint: Lookcarefully at Figure 3.14c and replace the alanine shown withglycine.)

3.7 Proteins: Primary and Secondary Structure

Proteins play several key roles in cell function. In essence, acell is what it is and does what it does because of the kindsand amounts of proteins it contains; that is, every differenttype of cell has a different complement of proteins. An un-derstanding of protein structure is therefore essential forunderstanding how cells work.

Two major classes of proteins are catalytic proteins(enzymes) and structural proteins. Enzymes are thecatalysts for chemical reactions that occur in cells (lChap-ters 5, 20, and 21). By contrast, structural proteins areintegral parts of the major structures of the cell: membranes,walls, cytoplasmic components, and so on. However, allproteins show certain basic features in common, and wediscuss these now.

Primary StructureAs we have said, proteins are polymers of amino acids cova-lently bonded by peptide bonds (Figure 3.13). Two amino acidsbonded by peptide linkage constitute a dipeptide, three aminoacids, a tripeptide, and so on. When many amino acids are co-valently linked via peptide bonds, they form a polypeptide.

cc

(b)

NH2H2N

COOH

C HH2N

CH3

COOH

CH

CH3

COOH

C NH2

CH3

COOH

CH

CH3

H

L-Alanine D-Alanine

(c)

HO

HO

HO

OH

HHO

C OHH

OH

CH2OH

O

C H

CH

H

H

CH2OH

D-Glucose L-Glucose

CO

OH

(a)

H

CH

C

CH

HC

C

C

bC C

a a

d db

Three-dimensional projection

Figure 3.14 Isomers. (a) Ball-and-stick model showing mirror images.(b) Enantiomers of glucose. (c) Enantiomers of the amino acid alanine.In the three-dimensional projection the arrow should be understood ascoming toward the viewer and the dashed line indicates a plane awayfrom the viewer. Note that no matter how the three-dimensional viewsare rotated, the L and D forms can never be superimposed. This is acharacteristic of enantiomers.

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play important roles in polypeptide secondary structure. Onecommon type of secondary structure is the �-helix. To envi-sion an α-helix, imagine a linear polypeptide wound arounda cylinder (Figure 3.15a). In this twisted structure, oxygenand nitrogen atoms from different amino acids becomepositioned close enough to allow hydrogen bonding. Thesehydrogen bonds give the α-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 theβ-sheet, the chain of amino acids in the polypeptide folds backand forth upon itself instead of forming a helix. However, as inthe α-helix, the folding in a β-sheet exposes hydrogen atomsthat can undergo hydrogen bonding (Figure 3.15b). Typically,a β-sheet secondary structure yields a polypeptide that israther rigid and α-helical secondary structures are more flexi-ble. Thus, an enzyme, for example, whose activity maydepend on its being rather flexible, may contain a high degreeof α-helix secondary structure. By contrast, a structural pro-tein that functions in cellular scaffolding may contain largeregions of β-sheet secondary structure.

Many polypeptides contain regions of both α-helix andβ-sheet secondary structure, the type of folding and its loca-tion in the molecule being determined by the primarystructure and the available opportunities for hydrogen bond-ing and hydrophobic interactions (see Figure 3.16). A typicalprotein 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 Structureand Denaturation

Once a polypeptide has achieved secondary structure it con-tinues to fold to form an even more stable molecule. Thisfolding results in a unique three-dimensional shape called thetertiary structure of the protein.

Like secondary structure, tertiary structure is ultimatelydetermined by primary structure. However, tertiary structureis also governed to some extent by the secondary structure ofthe molecule because the side chain of each amino acid in thepolypeptide is positioned in a specific way (Figure 3.15). Ifadditional hydrogen bonds, covalent bonds, hydrophobic in-teractions, or other atomic interactions are able to form, thepolypeptide 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 seeFigure 3.17) that are important for binding other molecules(for example, in the binding of a substrate to an enzyme or thebinding of DNA to a specific regulatory protein) (lSections5.5 and 9.2).

Frequently a polypeptide folds in such a way that adjacentsulfhydryl groups of cysteine residues are exposed. These free—SH groups can form a disulfide bond between the twoamino acids. If the two cysteine residues are located in dif-ferent polypeptides in a protein, the disulfide bond covalentlylinks the two molecules (Figure 3.16a). In addition, a singlepolypeptide chain can fold and bond to itself if a disulfidebond can form within the molecule.


Hydrogen bondsbetween distantamino acids(a) �-helix (b) �-sheet

CCC

C C C

C

C

CC C

CC C

C

C

C

CC

C

C CC

C C

CC

C

CC C

CC C

CC

C

CC

C CCC

CCCC

C C

CC CC

C C

O O OO O

O

O O

O

OO

O

OO

O

O O

O

O O

O

O O

OO

OO

RR

R R

R

RR R R

R R R

RRR

R R R

RRR

R R R

R R R

R

HH

H H

H

H H

H

H H

H

H H

H

HH

H

HHHH

HH

H

HH

HH

HH

HH

HH

HH

NN

NN

NN

NN

N

N N

NN

N

N N

N

N N

N

NN

N

NN

N

Hydrogen bondsbetween nearbyamino acids

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.

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Quaternary StructureIf a protein consists of two or more polypeptides, and manyproteins do, the number and type of polypeptides that formthe final protein molecule are referred to as its quaternarystructure (Figure 3.17). In proteins showing quaternarystructure, each polypeptide, called a subunit, contains pri-mary, secondary, and tertiary structure. Some proteins containmultiple copies of a single subunit. A protein containing twoidentical subunits, for example, would be called a homodimer.Other proteins may contain nonidentical subunits, eachpresent in one or more copies (a heterodimer, for example,contains one copy each of two different polypeptides). Thesubunits 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.

DenaturationWhen proteins are exposed to extremes of heat or pH or tocertain chemicals or metals that affect their folding, they mayundergo denaturation (Figure 3.18). Denaturation causesthe polypeptide chain to unfold, destroying the higher order(secondary, tertiary, and quaternary, if relevant) structure ofthe molecule. Depending on the severity of the denaturant ordenaturing conditions, the polypeptide may refold after thedenaturant is removed (Figure 3.18). Typically, however, de-natured proteins unfold such that their hydrophobic regionsbecome exposed and stick together to form protein aggregatesthat lack biological activity.

The biological properties of a protein are usually lostwhen it is denatured. Peptide bonds (Figure 3.13) are un-affected, however, and so a denatured molecule retains itsprimary structure. This shows that biological activity is notinherent in the primary structure of a protein but instead is afunction of the uniquely folded form of the molecule as ulti-mately directed by primary structure. In other words, folding


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Figure 3.16 Tertiary structure of polypeptides. (a) Insulin, a pro-tein containing two polypeptide chains; note how the B chain containsboth �-helix and �-sheet secondary structure and how disulfide link-ages (S–S) help in dictating folding patterns (tertiary structure). (b) Ribonuclease, a large protein with several regions of �-helix and �-sheet secondary structure.

A chain

B chain

(a) Insulin (b) Ribonuclease

β-sheet

α-helixS S

S S

SS

α Chains

β Chains

α Chains

β Chains(a) (b)

Figure 3.17 Quaternary structure of human hemoglobin.(a) There are two kinds of polypeptide in human hemoglobin, � chains(shown in blue and red) and � chains (shown in orange and yellow), buta total of four polypeptides in the final protein molecule (two � chainsand two � chains). Separate colors are used to distinguish each chain.(b) Molecular structure of human hemoglobin as determined by X-raycrystallography. In this view each � chain is red and each � chain is blue.

Harsh denaturation;100˚C

Gentle denaturation;urea

CoolRemove urea;reactivation

Active

protein

Active

protein

Inactive Inactive

Inactive

Figure 3.18 Denaturation of the protein ribonuclease. Ribonucleasestructure was shown in Figure 3.16b. Note how harsh denaturationpermanently destroys a molecule (from the standpoint of biologicalfunction) because of improper folding but primary structure is retained.

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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 destroyingmicroorganisms. For example, alcohols such as phenol andethanol are effective disinfectants because they readily pene-trate cells and irreversibly denature their proteins. Suchchemical agents are thus useful for disinfecting inanimateobjects such as surfaces and have enormous practical value inhousehold, hospital, and industrial disinfectant applications.We discuss disinfectants, along with other chemical and phys-ical agents used to destroy microorganisms, in Chapter 27.

Moving OnNow that we have reviewed the chemistry of cellular compo-nents, we are in a better position to understand the structuraldetails 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 propertiesof 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 codingfunctions of the cell, the essential genetic events carried out byall cells. We discuss molecular biology in Chapters 7–9.

As the contemporary microbiologist Norman Pace hasput 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 agrasp 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 aminoacid sequence, but the folding (higher order structure) of thepolypeptide determines how the protein functions in the cell.

❚ Define the terms primary, secondary, and tertiary withrespect to protein structure.

❚ How does a polypeptide differ from a protein?

❚ What secondary structural features tend to make β-sheetproteins more rigid than α-helices?

❚ Describe the number and kinds of polypeptides present in ahomotetrameric protein.

❚ Describe the structural and biological effects of the denatu-ration of a protein. Of what practical value is knowledge ofprotein denaturation?


Amino acid one of the 22 different monomersthat make up proteins; chemically, a two-carbon carboxylic acid containing an aminogroup and a characteristic substituent on thealpha carbon

Covalent bond a chemical bond in whichelectrons are shared between two atoms

Denaturation destruction of the folding prop-erties of a protein leading (usually) to proteinaggregation and loss of biological activity

Domain in the context of proteins, a portionof the protein typically possessing a specificstructure or function

DNA (deoxyribonucleic acid) a polymer of de-oxyribonucleotides linked by phosphodiesterbonds that carries genetic information

Enantiomer a form of a molecule that is themirror image of another form of the samemolecule

Enzyme a protein or an RNA that catalyzes aspecific 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 oflipids of Bacteria and Eukarya

Glycosidic bond a covalent bond linkingsugars together in a polysaccharide

Hydrogen bond a weak chemical interactionbetween a hydrogen atom and a second,more electronegative element, usually anoxygen or nitrogen atom

Isomers two molecules with the samemolecular formula but a difference instructure

Lipid a polar compound such as glycerolbonded to fatty acids or other hydrophobicmolecules by ester or ether linkage, oftenalso containing other groups, such as phos-phate or sugars

Macromolecule a polymer of covalentlylinked monomeric units, such as DNA, RNA,polysaccharides, and lipids

Molecule two or more atoms chemicallybonded to one another

Monomer a small molecule that is a buildingblock for larger molecules

Nonpolar possessing hydrophobic (water-repelling) characteristics and not easilydissolved 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 moremolecules of phosphate, and a sugar, eitherribose (in RNA) or deoxyribose (in DNA)

Peptide bond a type of covalent bond linkingamino acids in a polypeptide

Phosphodiester bond a type of covalentbond linking nucleotides together in apolynucleotide

Polar possessing hydrophilic (water-loving)characteristics and generally water soluble

Polymer a large molecule made up ofmonomers

Polynucleotide a polymer of nucleotidesbonded to one another by covalent bondscalled phosphodiester bonds

Polypeptide a polymer of amino acidsbonded to one another by peptide bonds

Review of Key Terms

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Polysaccharide a polymer of sugar unitsbonded to one another by glycosidic bonds

Primary structure in an informationalmacromolecule such as a polypeptide or anucleic acid, the precise sequence ofmonomeric units

Protein a polypeptide or group ofpolypeptides forming a molecule of specificbiological function

Purine one of the nitrogen bases of nucleicacids that contain two fused rings; adenineand guanine

Pyrimidine one of the nitrogen bases ofnucleic acids that contain a single ring; cyto-sine, thymine, and uracil

Quaternary structure in proteins, the num-ber and types of individual polypeptides inthe final protein molecule

RNA (ribonucleic acid) a polymer of ribonu-cleotides linked by phosphodiester bondsthat plays many roles in cells, in particular,during protein synthesis

Secondary structure the initial pattern offolding of a polypeptide or a polynucleotide,

usually dictated by opportunities for hydro-gen bonding

Tertiary structure the final folded structureof a polypeptide that has previously attainedsecondary structure

1. Which are the major elements found in living organisms? Whyare 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 ofglucose (Sections 3.1 and 3.3)?

3. Refer to the structure of the nitrogen base cytosine shown inFigure 3.1. Draw this structure and then label the positions ofall 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 andlist the monomers of which they are composed. Which classesof 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. Howdoes a triglyceride differ from a complex lipid (Section 3.4)?

6. Examine the structures of the triglyceride and of phosphatidylethanolamine shown in Figure 3.7. How might the substitutionof 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 showdistinct differences as well. List three ways in which RNAdiffers chemically or physically from DNA. What is the cellularfunction of DNA and RNA (Section 3.5)?

8. Why are amino acids so named? Write a general structure foran amino acid. What is the importance of the R group to finalprotein 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 bydenaturation (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 anucleic acid. All of these bonds are examples of ___________bonds, which are chemically much stronger than weak bonds,such as ___________, ___________, and ___________

Review Questions

1. Observe the following nucleotide sequences of RNA: (a) GUCAAAGAC, (b) ACGAUAACC. Can either of these RNAmolecules have secondary structure? If so, draw the potentialsecondary structure(s).

2. A few soluble (cytoplasmic) proteins contain a high content ofhydrophobic 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 verysalty environments, contain over 5 molar (M) potassium (K�).Because of this high K� content, many cytoplasmic proteins ofHalobacterium cells are enriched in two specific amino acidsthat are present in much higher proportions in Halobacteriumproteins than in functionally similar proteins from Escherichiacoli (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 inhabitantof 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 growsoptimally in boiling hot springs is put in the same beaker, similarchanges do not occur. Explain.

5. Review Figure 3.6b and then describe the differences that makeeach of these polymers unique. If all of the glycosidic bonds inthese polymers were hydrolyzed, what single molecule wouldremain?

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”?

Application Questions

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