The Chemical Building Blocks of Life - Basic Knowledge 101 Blocks of Life.pdf · The Chemical...

35

3The Chemical Building

Blocks of Life

Concept Outline

3.1 Molecules are the building blocks of life.

The Chemistry of Carbon. Because individual carbonatoms can form multiple covalent bonds, organic moleculescan be quite complex.

3.2 Proteins perform the chemistry of the cell.

The Many Functions of Proteins. Proteins can be cata-lysts, transporters, supporters, and regulators.Amino Acids Are the Building Blocks of Proteins. Proteinsare long chains of various combinations of amino acids.A Protein’s Function Depends on the Shape of theMolecule. A protein’s shape is determined by its amino acidsequence.How Proteins Fold Into Their Functional Shape. Thedistribution of nonpolar amino acids along a protein chainlargely determines how the protein folds.How Proteins Unfold. When conditions such as pH ortemperature fluctuate, proteins may denature or unfold.

3.3 Nucleic acids store and transfer genetic information.

Information Molecules. Nucleic acids store information incells. RNA is a single-chain polymer of nucleotides, whileDNA possesses two chains twisted around each other.

3.4 Lipids make membranes and store energy.

Phospholipids Form Membranes. The spontaneous ag-gregation of phospholipids in water is responsible for theformation of biological membranes.Fats and Other Kinds of Lipids. Organisms utilize a widevariety of water-insoluble molecules.Fats as Food. Fats are very efficient energy storagemolecules because of their high proportion of C—H bonds.

3.5 Carbohydrates store energy and provide buildingmaterials.

Simple Carbohydrates. Sugars are simple carbohydrates,often consisting of six-carbon rings.Linking Sugars Together. Sugars can be linked together toform long polymers, or polysaccharides.Structural Carbohydrates. Structural carbohydrates likecellulose are chains of sugars linked in a way that enzymescannot easily attack.

Molecules are extremely small compared with the fa-miliar world we see about us. Imagine: there are

more water molecules in a cup than there are stars in thesky. Many other molecules are gigantic, compared with wa-ter, consisting of thousands of atoms. These atoms are or-ganized into hundreds of smaller molecules that are linkedtogether into long chains (figure 3.1). These enormousmolecules, almost always synthesized by living things, arecalled macromolecules. As we shall see, there are four gen-eral types of macromolecules, the basic chemical buildingblocks from which all organisms are assembled.

FIGURE 3.1Computer-generated model of a macromolecule. Pictured isan enzyme responsible for releasing energy from sugar. Thiscomplex molecule consists of hundreds of different amino acidslinked into chains that form the characteristic coils and folds seenhere.

Biological Macromolecules

Some organic molecules in organisms are small and sim-ple, containing only one or a few functional groups. Oth-ers are large complex assemblies called macromolecules.In many cases, these macromolecules are polymers, mole-cules built by linking together a large number of small,similar chemical subunits, like railroad cars coupled toform a train. For example, complex carbohydrates likestarch are polymers of simple ring-shaped sugars, pro-teins are polymers of amino acids, and nucleic acids(DNA and RNA) are polymers of nucleotides. Biologicalmacromolecules are traditionally grouped into four majorcategories: proteins, nucleic acids, lipids, and carbohy-drates (table 3.1).

36 Part I The Origin of Living Things

The Chemistry of CarbonIn chapter 2 we discussed how atoms combine to formmolecules. In this chapter, we will focus on organic mole-cules, those chemical compounds that contain carbon. Theframeworks of biological molecules consist predominantlyof carbon atoms bonded to other carbon atoms or to atomsof oxygen, nitrogen, sulfur or hydrogen. Because carbonatoms possess four valence electrons and so can form fourcovalent bonds, molecules containing carbon can formstraight chains, branches, or even rings. As you can imag-ine, all of these possibilities generate an immense range ofmolecular structures and shapes.

Organic molecules consisting only of carbon and hydro-gen are called hydrocarbons. Covalent bonds between car-bon and hydrogen are energy-rich. We use hydrocarbonsfrom fossil fuels as a primary source of energy today.Propane gas, for example, is a hydrocarbon consisting of achain of three carbon atoms, with eight hydrogen atomsbound to it:

H H H| | |

H—C—C—C—H| | |H H H

Because carbon-hydrogen covalent bonds store consider-able energy, hydrocarbons make good fuels. Gasoline, forexample, is rich in hydrocarbons.

Functional Groups

Carbon and hydrogen atoms both have very similar elec-tronegativities, so electrons in C—C and C—H bonds areevenly distributed, and there are no significant differencesin charge over the molecular surface. For this reason, hy-drocarbons are nonpolar. Most organic molecules that areproduced by cells, however, also contain other atoms. Be-cause these other atoms often have different electronegativ-ities, molecules containing them exhibit regions of positiveor negative charge, and so are polar. These molecules canbe thought of as a C—H core to which specific groups ofatoms called functional groups are attached. For example,a hydrogen atom bonded to an oxygen atom (—OH) is afunctional group called a hydroxyl group.

Functional groups have definite chemical properties thatthey retain no matter where they occur. The hydroxylgroup, for example, is polar, because its oxygen atom, beingvery electronegative, draws electrons toward itself (as wesaw in chapter 2). Figure 3.2 illustrates the hydroxyl groupand other biologically important functional groups. Mostchemical reactions that occur within organisms involve thetransfer of a functional group as an intact unit from onemolecule to another.


Hydroxyl

Carbonyl

Carboxyl

Amino

Sulfhydryl

Phosphate

Methyl

Carbohydrates,alcohols

Amino acids,vinegar

Group StructuralFormula

Ball-and-Stick Model

Found In:

Formaldehyde

Ammonia

Proteins,rubber

Phospholipids,nucleic acids,

ATP

Methanegas

HS

O–P

O–

O

O

HC

H

H

OH

O

OH

C

H

H

N

C

O

H

H

O

O–PO

H

N

S

HO

O–

H

H

C

H

H

O

C

O

O

C

FIGURE 3.2The primary functional chemical groups. These groups tend toact as units during chemical reactions and confer specific chemicalproperties on the molecules that possess them. Amino groups, forexample, make a molecule more basic, while carboxyl groupsmake a molecule more acidic.

Building Macromolecules

Although the four categories of macromolecules contain dif-ferent kinds of subunits, they are all assembled in the samefundamental way: to form a covalent bond between two sub-unit molecules, an —OH group is removed from one sub-unit and a hydrogen atom (H) is removed from the other(figure 3.3a). This condensation reaction is called a dehy-dration synthesis, because the removal of the —OH groupand H during the synthesis of a new molecule in effect con-stitutes the removal of a molecule of water (H2O). For everysubunit that is added to a macromolecule, one water mole-cule is removed. Energy is required to break the chemicalbonds when water is extracted from the subunits, so cellsmust supply energy to assemble macromolecules. These andother biochemical reactions require that the reacting sub-stances be held close together and that the correct chemicalbonds be stressed and broken. This process of positioningand stressing, termed catalysis, is carried out in cells by aspecial class of proteins known as enzymes.

Cells disassemble macromolecules into their constituentsubunits by performing reactions that are essentially the re-verse of dehydration—a molecule of water is added insteadof removed (figure 3.3b). In this process, which is calledhydrolysis (Greek hydro, “water” + lyse, “break”), a hydro-gen atom is attached to one subunit and a hydroxyl groupto the other, breaking a specific covalent bond in themacromolecule. Hydrolytic reactions release the energythat was stored in the bonds that were broken.

Polymers are large molecules consisting of long chainsof similar subunits joined by dehydration reactions. In adehydration reaction, a hydroxyl (—OH) group isremoved from one subunit and a hydrogen atom (H) isremoved from the other.

Chapter 3 The Chemical Building Blocks of Life 37

Table 3.1 Macromolecules

Macromolecule Subunit Function Example

PROTEINS

GlobularStructural

NUCLEIC ACIDS

DNARNA

LIPIDS

FatsPhospholipids

Prostaglandins

SteroidsTerpenes

CARBOHYDRATES

Starch, glycogenCelluloseChitin

HemoglobinHair; silk

ChromosomesMessenger RNA

Butter; corn oil; soapLecithin

Prostaglandin E (PGE)

Cholesterol; estrogenCarotene; rubber

PotatoesPaper; strings of celeryCrab shells

Amino acidsAmino acids

NucleotidesNucleotides

Glycerol and three fatty acidsGlycerol, two fatty acids,phosphate, and polar R groupsFive-carbon rings with twononpolar tailsFour fused carbon ringsLong carbon chains

GlucoseGlucose

Modified glucoseCatalysis; transportSupport

Encodes genesNeeded for gene expression

Energy storageCell membranes

Chemical messengers

Membranes; hormonesPigments; structural

Energy storageCell wallsStructural support

H2O

H2O

HO

HO H

HO H

H HHO

Energy

Dehydration synthesis

HO H HHO

Energy

Hydrolysis

(a)

(b)

FIGURE 3.3Making and breakingmacromolecules.(a) Biologicalmacromolecules arepolymers formed bylinking subunitstogether. Thecovalent bondbetween the subunitsis formed bydehydration synthesis,an energy-requiringprocess that creates awater molecule forevery bond formed. (b)Breaking the bondbetween subunitsrequires the returningof a water moleculewith a subsequentrelease of energy, aprocess calledhydrolysis.

The Many Functions of ProteinsWe will begin our discussion of macromolecules that makeup the bodies of organisms with proteins (see table 3.1). Theproteins within living organisms are immensely diverse instructure and function (table 3.2 and figure 3.4).

1. Enzyme catalysis. We have already encounteredone class of proteins, enzymes, which are biologicalcatalysts that facilitate specific chemical reactions. Be-cause of this property, the appearance of enzymes wasone of the most important events in the evolution oflife. Enzymes are globular proteins, with a three-dimensional shape that fits snugly around the chemi-

cals they work on, facilitating chemical reactions bystressing particular chemical bonds.

2. Defense. Other globular proteins use their shapesto “recognize” foreign microbes and cancer cells.These cell surface receptors form the core of thebody’s hormone and immune systems.

3. Transport. A variety of globular proteins transportspecific small molecules and ions. The transport pro-tein hemoglobin, for example, transports oxygen inthe blood, and myoglobin, a similar protein, transportsoxygen in muscle. Iron is transported in blood by theprotein transferrin.



Table 3.2 The Many Functions of Proteins

Function Class of Protein Examples Use

Metabolism (Catalysis)

Defense

Cell recognitionTransport throughout body

Membrane transport

Structure/Support

Motion

Osmotic regulation

Regulation of gene actionRegulation of body functions

Storage

Enzymes

Immunoglobulins

ToxinsCell surface antigensGlobins

Transporters

Fibers

Muscle

Albumin

RepressorsHormones

Ion binding

Hydrolytic enzymesProteasesPolymerasesKinases

Antibodies

Snake venomMHC proteinsHemoglobinMyoglobinCytochromesSodium-potassium pumpProton pumpAnion channelsCollagenKeratinFibrinActinMyosinSerum albumin

lac repressorInsulinVasopressin

Oxytocin

FerritinCaseinCalmodulin

Cleave polysaccharidesBreak down proteinsProduce nucleic acidsPhosphorylate sugars andproteinsMark foreign proteins foreliminationBlock nerve function“Self” recognitionCarries O2 and CO2 in bloodCarries O2 and CO2 in muscleElectron transportExcitable membranesChemiosmosisTransport Cl– ionsCartilageHair, nailsBlood clotContraction of muscle fibersContraction of muscle fibersMaintains osmotic concentrationof bloodRegulates transcriptionControls blood glucose levelsIncreases water retention bykidneysRegulates uterine contractionsand milk productionStores iron, especially in spleenStores ions in milkBinds calcium ions

4. Support. Fibrous, or threadlike, proteins play struc-tural roles; these structural proteins (see figure 3.4) in-clude keratin in hair, fibrin in blood clots, and col-lagen, which forms the matrix of skin, ligaments,tendons, and bones and is the most abundant proteinin a vertebrate body.

5. Motion. Muscles contract through the sliding mo-tion of two kinds of protein filament: actin and myo-sin. Contractile proteins also play key roles in thecell’s cytoskeleton and in moving materials withincells.

6. Regulation. Small proteins called hormones serveas intercellular messengers in animals. Proteins alsoplay many regulatory roles within the cell, turning onand shutting off genes during development, for exam-ple. In addition, proteins also receive information, act-ing as cell surface receptors.

Proteins carry out a diverse array of functions, includingcatalysis, defense, transport of substances, motion, andregulation of cell and body functions.


(a) (b)

(c) (d) (e)

FIGURE 3.4Some of the more common structural proteins. (a) Collagen: strings of a tennis racket from gut tissue; (b) fibrin: scanning electronmicrograph of a blood clot (3000×); (c) keratin: a peacock feather; (d) silk: a spider’s web; (e) keratin: human hair.

Amino Acids Are the Building Blocksof ProteinsAlthough proteins are complex and versatile molecules, theyare all polymers of only 20 amino acids, in a specific order.Many scientists believe amino acids were among the firstmolecules formed in the early earth. It seems highly likelythat the oceans that existed early in the history of the earthcontained a wide variety of amino acids.

Amino Acid Structure

An amino acid is a molecule containing an amino group(—NH2), a carboxyl group (—COOH), and a hydrogenatom, all bonded to a central carbon atom:

R|

H2N—C—COOH|H

Each amino acid has unique chemical properties deter-mined by the nature of the side group (indicated by R) cova-lently bonded to the central carbon atom. For example,when the side group is —CH2OH, the amino acid (serine) ispolar, but when the side group is —CH3, the amino acid(alanine) is nonpolar. The 20 common amino acids aregrouped into five chemical classes, based on their sidegroups:

1. Nonpolar amino acids, such as leucine, often have Rgroups that contain —CH2 or —CH3.

2. Polar uncharged amino acids, such as threonine, haveR groups that contain oxygen (or only —H).

3. Ionizable amino acids, such as glutamic acid, have Rgroups that contain acids or bases.

4. Aromatic amino acids, such as phenylalanine, have Rgroups that contain an organic (carbon) ring with al-ternating single and double bonds.

5. Special-function amino acids have unique individualproperties; methionine often is the first amino acid ina chain of amino acids, proline causes kinks in chains,and cysteine links chains together.

Each amino acid affects the shape of a protein differentlydepending on the chemical nature of its side group. Portionsof a protein chain with numerous nonpolar amino acids, forexample, tend to fold into the interior of the protein by hy-drophobic exclusion.

Proteins Are Polymers of Amino Acids

In addition to its R group, each amino acid, when ionized,has a positive amino (NH3

+) group at one end and a nega-tive carboxyl (COO–) group at the other end. The aminoand carboxyl groups on a pair of amino acids can undergo acondensation reaction, losing a molecule of water and

forming a covalent bond. A covalent bond that links twoamino acids is called a peptide bond (figure 3.5). The twoamino acids linked by such a bond are not free to rotatearound the N—C linkage because the peptide bond has apartial double-bond character, unlike the N—C and C—Cbonds to the central carbon of the amino acid. The stiffnessof the peptide bond is one factor that makes it possible forchains of amino acids to form coils and other regularshapes.

A protein is composed of one or more long chains, orpolypeptides, composed of amino acids linked by peptidebonds. It was not until the pioneering work of FrederickSanger in the early 1950s that it became clear that eachkind of protein had a specific amino acid sequence. Sangersucceeded in determining the amino acid sequence of insu-lin and in so doing demonstrated clearly that this proteinhad a defined sequence, the same for all insulin moleculesin the solution. Although many different amino acids occurin nature, only 20 commonly occur in proteins. Figure 3.6illustrates these 20 “common” amino acids and their sidegroups.

A protein is a polymer containing a combination of upto 20 different kinds of amino acids. The amino acidsfall into five chemical classes, each with differentproperties. These properties determine the nature ofthe resulting protein.


H

—

H — N — C — OH

O

— C

—

H

—

H

H2O

—

H — N — C — OH

O

— C

—

H

—

Amino acidAmino acid

H

—

H — N — C —

O

— —

— —

— C

—

H

—

H

—

N — C — OH

O

— —

— —

— C

—

H

—

Polypeptide chain

R R

R R

FIGURE 3.5The peptide bond. A peptide bond forms when the —NH2 endof one amino acid joins to the —COOH end of another. Becauseof the partial double-bond nature of peptide bonds, the resultingpeptide chain cannot rotate freely around these bonds.


Proline(Pro)

CH2 CH — C — OH—

—

H

N

— ——

—

CH2 CH2

—

O

Methionine(Met)

CH2

H2N — C — C — OH

——

H O

— —

—

CH2

—

S

—

CH3

Cysteine(Cys)

CH2

H2N — C — C — OH

——

H O

— —

—

SH

SPECIAL STRUCTURAL PROPERTY

CH3

H2N — C — C — OH

——

H O

— —

CH

H2N — C — C — OH

——

H O

— —

——CH3CH3

CH2

H2N — C — C — OH—

—

H O

— —

——CH3CH3

—

CH CH2

H2N — C — C — OH

——

H O

— —

—

CH3

H — C — CH3

—

CH2

H2N — C — C — OH

——

H O

— —

—

CH2

H2N — C — C — OH

——

H O

NH

—

C

— ——

———

—

Alanine(Ala)

Leucine(Leu)

Isoleucine(Ile)

Phenylalanine(Phe)

Tryptophan(Trp)

CH2

H2N — C — C — OH

——

H O

— —

OH

—

H — C — OH

H2N — C — C — OH

——

H O

— —

CH3

—

CH2

H2N — C — C — OH

——

H O

— —

—

CH2

—

C—NH2

——O

CH2

H2N — C — C — OH

——

H O

OH

—

— ——

—

C

H2N — C — C — OH

——

H O

—NH2

—

— —

——

CH2

O

H

H2N — C — C — OH

——

H O

— —

Tyrosine(Tyr)

Glutamine(Gln)

Asparagine(Asn)

Threonine(Thr)

Serine(Ser)

Glycine(Gly)

CH2

H2N — C — C — OH

——

H O

— —

—

CH2

—

C———

O O–

CH2

H2N — C — C — OH

——

H O

CH2

—

NH

—

CH2

——

— —

——C NH2+

—

NH2

CH2

H2N — C — C — OH

——

H O

— —

—

CH2 — NH3+

—

CH2

CH2

—

CH2

H2N — C — C — OH

——

H O

—

C — N

— —

— —

HC — N

—CH

H

H2N — C — C — OH

——

H O

— —

CH2

—

C———

O O–

Glutamicacid (Glu)

Asparticacid (Asp)

Histidine(His)

Lysine(Lys)

Arginine(Arg)

Ionizable (charged)

Polar uncharged

Nonpolar

NONAROMATIC AROMATIC

H+——

Valine(Val)

FIGURE 3.6The 20 common amino acids. Each amino acid has thesame chemical backbone, but differs in the side, or R, groupit possesses. Six of the amino acids are nonpolar becausethey have —CH2 or —CH3 in their R groups. Two of thesix are bulkier because they contain ring structures, whichclassifies them also as aromatic. Another six are polarbecause they have oxygen or just hydrogen in their Rgroups; these amino acids, which are uncharged, differ fromone another in how polar they are. Five other amino acidsare polar and, because they have a terminal acid or base intheir R group, are capable of ionizing to a charged form.The remaining three have special chemical properties thatallow them to help form links between protein chains orkinks in proteins.

A Protein’s Function Dependson the Shape of the MoleculeThe shape of a protein is very important because itdetermines the protein’s function. If we picture apolypeptide as a long strand similar to a reed, a pro-tein might be the basket woven from it.

Overview of Protein Structure

Proteins consist of long amino acid chains foldedinto complex shapes. What do we know about theshape of these proteins? One way to study theshape of something as small as a protein is to lookat it with very short wavelength energy—with Xrays. X-ray diffraction is a painstaking procedurethat allows the investigator to build up a three-dimensional picture of the position of each atom.The first protein to be analyzed in this way wasmyoglobin, soon followed by the related proteinhemoglobin. As more and more proteins were add-ed to the list, a general principle became evident:in every protein studied, essentially all the internalamino acids are nonpolar ones, amino acids such asleucine, valine, and phenylalanine. Water’s tenden-cy to hydrophobically exclude nonpolar moleculesliterally shoves the nonpolar portions of the aminoacid chain into the protein’s interior. This posi-tions the nonpolar amino acids in close contactwith one another, leaving little empty space inside.Polar and charged amino acids are restricted to thesurface of the protein except for the few that playkey functional roles.

Levels of Protein Structure

The structure of proteins is traditionally discussedin terms of four levels of structure, as primary, sec-ondary, tertiary, and quaternary (figure 3.7). Becauseof progress in our knowledge of protein structure,two additional levels of structure are increasinglydistinguished by molecular biologists: motifs and do-mains. Because these latter two elements play im-portant roles in coming chapters, we introducethem here.

Primary Structure. The specific amino acid se-quence of a protein is its primary structure. Thissequence is determined by the nucleotide se-quence of the gene that encodes the protein. Be-cause the R groups that distinguish the variousamino acids play no role in the peptide backboneof proteins, a protein can consist of any sequenceof amino acids. Thus, a protein containing 100amino acids could form any of 20100 different ami-no acid sequences (that’s the same as 10130, or 1


N

N

N

NN

HH

HH

H

C

CC

C

O

O

O

CC

C

C

CC

OC

O

NN

H HC

OC

C

OC

H

NN

H

O

O

C

CC

β-pleatedsheet

α helix

C

OHO

N

HH

Tertiarystructure

Secondarystructure

Primarystructure

Quaternarystructure

(c)

(b)

(a)

(d)

H

H

H

H

H

H

H

H

H

HO

O

O

O

O

O

O

OO

O

C

CC

C C

CC

C

CC

CC

CC

CC

C

C

CC

C C NNN

N N N N

N

N

N

FIGURE 3.7Levels of protein structure. The amino acid sequence of a protein is calledits (a) primary structure. Hydrogen bonds form between nearby amino acids,producing (b) fold-backs called beta-pleated sheets and coils called alphahelices. These fold-backs and coils constitute the protein’s secondarystructure. A globular protein folds up on itself further to assume a three-dimensional (c) tertiary structure. Many proteins aggregate with otherpolypeptide chains in clusters; this clustering is called the (d) quaternarystructure of the protein.

followed by 130 zeros—more than the number of atomsknown in the universe). This is an important property ofproteins because it permits such great diversity.

Secondary Structure. The amino acid side groups arenot the only portions of proteins that form hydrogenbonds. The —COOH and —NH2 groups of the mainchain also form quite good hydrogen bonds—so good thattheir interactions with water might be expected to offsetthe tendency of nonpolar sidegroups to be forced into theprotein interior. Inspection of the protein structures deter-mined by X-ray diffraction reveals why they don’t—thepolar groups of the main chain form hydrogen bonds witheach other! Two patterns of H bonding occur. In one, hy-drogen bonds form along a single chain, linking one aminoacid to another farther down the chain. This tends to pullthe chain into a coil called an alpha (α) helix. In the otherpattern, hydrogen bonds occur across two chains, linkingthe amino acids in one chain to those in the other. Often,many parallel chains are linked, forming a pleated, sheet-like structure called a β-pleated sheet. The folding of theamino acid chain by hydrogen bonding into these charac-teristic coils and pleats is called a protein’s secondarystructure.

Motifs. The elements of secondary structure can combinein proteins in characteristic ways called motifs, or some-times “supersecondary structure.” One very common motifis the β α β motif, which creates a fold or crease; the so-called “Rossmann fold” at the core of nucleotide bindingsites in a wide variety of proteins is a β α β α β motif. A sec-ond motif that occurs in many proteins is the β barrel, a βsheet folded around to form a tube. A third type of motif,the α turn α motif, is important because many proteins useit to bind the DNA double helix.

Tertiary Structure. The final folded shape of a globularprotein, which positions the various motifs and folds non-polar side groups into the interior, is called a protein’s ter-tiary structure. A protein is driven into its tertiary structureby hydrophobic interactions with water. The final foldingof a protein is determined by its primary structure—by thechemical nature of its side groups. Many proteins can befully unfolded (“denatured”) and will spontaneously refoldback into their characteristic shape.

The stability of a protein, once it has folded into its 3-Dshape, is strongly influenced by how well its interior fitstogether. When two nonpolar chains in the interior are invery close proximity, they experience a form of molecularattraction called van der Waal’s forces. Individually quiteweak, these forces can add up to a strong attraction whenmany of them come into play, like the combined strengthof hundreds of hooks and loops on a strip of Velcro. Theyare effective forces only over short distances, however;there are no “holes” or cavities in the interior of proteins.That is why there are so many different nonpolar aminoacids (alanine, valine, leucine, isoleucine). Each has a dif-

ferent-sized R group, allowing very precise fitting of non-polar chains within the protein interior. Now you can un-derstand why a mutation that converts one nonpolar ami-no acid within the protein interior (alanine) into another(leucine) very often disrupts the protein’s stability; leucineis a lot bigger than alanine and disrupts the precise way thechains fit together within the protein interior. A change ineven a single amino acid can have profound effects on pro-tein shape and can result in loss or altered function of theprotein.

Domains. Many proteins in your body are encoded withinyour genes in functional sections called exons (exons will bediscussed in detail in chapter 15). Each exon-encoded sec-tion of a protein, typically 100 to 200 amino acids long,folds into a structurally independent functional unit called adomain. As the polypeptide chain folds, the domains foldinto their proper shape, each more-or-less independent ofthe others. This can be demonstrated experimentally by ar-tificially producing the fragment of polypeptide that formsthe domain in the intact protein, and showing that the frag-ment folds to form the same structure as it does in the intactprotein.

A single polypeptide chain connects the domains of aprotein, like a rope tied into several adjacent knots. Oftenthe domains of a protein have quite separate functions—onedomain of an enzyme might bind a cofactor, for example,and another the enzyme’s substrate.

Quaternary Structure. When two or more polypeptidechains associate to form a functional protein, the individ-ual chains are referred to as subunits of the protein. Thesubunits need not be the same. Hemoglobin, for example,is a protein composed of two α-chain subunits and two β-chain subunits. A protein’s subunit arrangement is calledits quaternary structure. In proteins composed of sub-units, the interfaces where the subunits contact one an-other are often nonpolar, and play a key role in transmit-ting information between the subunits about individualsubunit activities.

A change in the identity of one of these amino acids canhave profound effects. Sickle cell hemoglobin is a mutationthat alters the identity of a single amino acid at the cornerof the β subunit from polar glutamate to nonpolar valine.Putting a nonpolar amino acid on the surface creates a“sticky patch” that causes one hemoglobin molecule tostick to another, forming long nonfunctional chains andleading to the cell sickling characteristic of this hereditarydisorder.

Protein structure can be viewed at six levels: 1. theamino acid sequence, or primary structure; 2. coils andsheets, called secondary structure; 3. folds or creases,called motifs; 4. the three-dimensional shape, calledtertiary structure; 5. functional units, called domains;and 6. individual polypeptide subunits associated in aquaternary structure.


How Proteins Fold IntoTheir Functional ShapeHow does a protein fold into a specificshape? Nonpolar amino acids play a keyrole. Until recently, investigatorsthought that newly made proteins foldspontaneously as hydrophobic interac-tions with water shove nonpolar aminoacids into the protein interior. We nowknow this is too simple a view. Proteinchains can fold in so many differentways that trial and error would simplytake too long. In addition, as the openchain folds its way toward its final form,nonpolar “sticky” interior portions areexposed during intermediate stages. Ifthese intermediate forms are placed in atest tube in the same protein environ-ment that occurs in a cell, they stick toother unwanted protein partners, form-ing a gluey mess.

Chaperonins

How do cells avoid this? A vital cluecame in studies of unusual mutationsthat prevented viruses from replicatingin E. coli bacterial cells—it turned outthe virus proteins could not fold prop-erly! Further study revealed that nor-mal cells contain special proteins calledchaperonins that help new proteinsfold correctly (figure 3.8). When the E.coli gene encoding its chaperone pro-tein is disabled by mutation, the bacte-ria die, clogged with lumps of incor-rectly folded proteins. Fully 30% of thebacteria’s proteins fail to fold to theright shape.

Molecular biologists have now identified more than 17kinds of proteins that act as molecular chaperones. Manyare heat shock proteins, produced in greatly elevatedamounts if a cell is exposed to elevated temperature; hightemperatures cause proteins to unfold, and heat shockchaperonins help the cell’s proteins refold.

There is considerable controversy about how chaper-onins work. It was first thought that they provided a pro-tected environment within which folding could take placeunhindered by other proteins, but it now seems more like-ly that chaperonins rescue proteins that are caught in awrongly folded state, giving them another chance to foldcorrectly. When investigators “fed” a deliberately mis-folded protein called malate dehydrogenase to chaper-onins, the protein was rescued, refolding to its activeshape.

Protein Folding and Disease

There are tantalizing suggestions that chaperone proteindeficiencies may play a role in certain diseases by failing tofacilitate the intricate folding of key proteins. Cystic fibrosisis a hereditary disorder in which a mutation disables a pro-tein that plays a vital part in moving ions across cell mem-branes. In at least some cases, the vital membrane proteinappears to have the correct amino acid sequence, but fails tofold to its final form. It has also been speculated that chaper-one deficiency may be a cause of the protein clumping inbrain cells that produces the amyloid plaques characteristicof Alzheimer’s disease.

Proteins called chaperones aid newly produced proteinsto fold properly.


Correctlyfolded protein

Unfoldedprotein

Chaperone proteins present

Chaperone proteins absent

Unfolded

Incorrectly foldedEnzymedegradationof protein

FIGURE 3.8A current model of protein folding. A newly synthesized protein rapidly folds intocharacteristic motifs composed of � helices and � sheets, but these elements of structure areonly roughly aligned in an open conformation. Subsequent folding occurs more slowly, bytrial and error. This process is aided by chaperone proteins, which appear to recognizeimproperly folded proteins and unfold them, giving them another chance to fold properly.Eventually, if proper folding is not achieved, the misfolded protein is degraded byproteolytic enzymes.

How Proteins UnfoldIf a protein’s environment is altered, the proteinmay change its shape or even unfold. This pro-cess is called denaturation. Proteins can be de-natured when the pH, temperature, or ionicconcentration of the surrounding solution ischanged. When proteins are denatured, they areusually rendered biologically inactive. This isparticularly significant in the case of enzymes.Because practically every chemical reaction in aliving organism is catalyzed by a specific en-zyme, it is vital that a cell’s enzymes remainfunctional. That is the rationale behind tradi-tional methods of salt-curing and pickling: priorto the ready availability of refrigerators andfreezers, the only practical way to keep microor-ganisms from growing in food was to keep thefood in a solution containing high salt or vine-gar concentrations, which denatured the en-zymes of microorganisms and kept them fromgrowing on the food.

Most enzymes function within a very narrowrange of physical parameters. Blood-borne en-zymes that course through a human body at apH of about 7.4 would rapidly become dena-tured in the highly acidic environment of thestomach. On the other hand, the protein-degrading enzymes that function at a pH of 2 orless in the stomach would be denatured in thebasic pH of the blood. Similarly, organisms that live nearoceanic hydrothermal vents have enzymes that work well atthe temperature of this extreme environment (over 100°C).They cannot survive in cooler waters, because their en-zymes would denature at lower temperatures. Any givenorganism usually has a “tolerance range” of pH, tempera-ture, and salt concentration. Within that range, its enzymesmaintain the proper shape to carry out their biologicalfunctions.

When a protein’s normal environment is reestablishedafter denaturation, a small protein may spontaneously re-fold into its natural shape, driven by the interactions be-tween its nonpolar amino acids and water (figure 3.9).Larger proteins can rarely refold spontaneously becauseof the complex nature of their final shape. It is importantto distinguish denaturation from dissociation. The foursubunits of hemoglobin (figure 3.10) may dissociate intofour individual molecules (two α-globin and two β-globin) without denaturation of the folded globin pro-teins, and will readily reassume their four-subunit quater-nary structure.

Every globular protein has a narrow range of conditionsin which it folds properly; outside that range, proteinstend to unfold.


Reducin

agent

—N—C—

H H O

CH2

— ——

— —

Disulfide

—C—C—

—

———

O H H

CH2

—

—

S

—

S

—

Cooling orremoval ofurea

Heating oraddition ofurea

Unfoldedribonuclease

Reducedribonuclease

Nativeribonuclease

FIGURE 3.9Primary structure determines tertiary structure. When the proteinribonuclease is treated with reducing agents to break the covalent disulfide bondsthat cross-link its chains, and then placed in urea or heated, the protein denatures(unfolds) and loses its enzymatic activity. Upon cooling or removal of urea, itrefolds and regains its enzymatic activity. This demonstrates that no informationbut the amino acid sequence of the protein is required for proper folding: theprimary structure of the protein determines its tertiary structure.

Beta chainsHeme group

Alpha chains

FIGURE 3.10The four subunits of hemoglobin. The hemoglobin molecule ismade of four globin protein subunits, informally referred to aspolypeptide chains. The two lower α chains, identical α-globinproteins, are shaded pink; the two upper β chains, identical β-globin proteins, are shaded blue.

Information MoleculesThe biochemical activity of a cell depends on production ofa large number of proteins, each with a specific sequence.The ability to produce the correct proteins is passed be-tween generations of organisms, even though the proteinmolecules themselves are not.

Nucleic acids are the information storage devices ofcells, just as disks or tapes store the information that com-puters use, blueprints store the information that buildersuse, and road maps store the information that tourists use.There are two varieties of nucleic acids: deoxyribonucleicacid (DNA; figure 3.11) and ribonucleic acid (RNA). Theway in which DNA encodes the information used to as-semble proteins is similar to the way in which the letterson a page encode information (see chapter 14). Uniqueamong macromolecules, nucleic acids are able to serve astemplates to produce precise copies of themselves, so thatthe information that specifies what an organism is can becopied and passed down to its descendants. For this rea-son, DNA is often referred to as the hereditary material.Cells use the alternative form of nucleic acid, RNA, toread the cell’s DNA-encoded information and direct thesynthesis of proteins. RNA is similar to DNA in structureand is made as a transcripted copy of portions of theDNA. This transcript passes out into the rest of the cell,where it serves as a blueprint specifying a protein’s aminoacid sequence. This process will be described in detail inchapter 15.

“Seeing” DNA

DNA molecules cannot be seen with an optical micro-scope, which is incapable of resolving anything smallerthan 1000 atoms across. An electron microscope canimage structures as small as a few dozen atoms across, butstill cannot resolve the individual atoms of a DNA strand.This limitation was finally overcome in the last decadewith the introduction of the scanning-tunneling micro-scope (figure 3.12).

How do these microscopes work? Imagine you are in adark room with a chair. To determine the shape of thechair, you could shine a flashlight on it, so that the lightbounces off the chair and forms an image on your eye.That’s what optical and electron microscopes do; in the lat-ter, the “flashlight” emits a beam of electrons instead oflight. You could, however, also reach out and feel thechair’s surface with your hand. In effect, you would be put-ting a probe (your hand) near the chair and measuring howfar away the surface is. In a scanning-tunneling microscope,computers advance a probe over the surface of a moleculein steps smaller than the diameter of an atom.



FIGURE 3.11The first photograph of a DNA molecule. This micrograph,with sketch below, shows a section of DNA magnified a milliontimes! The molecule is so slender that it would take 50,000 ofthem to equal the diameter of a human hair.

FIGURE 3.12A scanning tunneling micrograph of DNA (false color;2,000,000×). The micrograph shows approximately three turns ofthe DNA double helix (see figure 3.15).

The Structure of Nucleic Acids

Nucleic acids are long polymers of repeating subunits callednucleotides. Each nucleotide consists of three components:a five-carbon sugar (ribose in RNA and deoxyribose inDNA); a phosphate (—PO4) group; and an organic nitrogen-containing base (figure 3.13). When a nucleic acid polymerforms, the phosphate group of one nucleotide binds to thehydroxyl group of another, releasing water and forming aphosphodiester bond. A nucleic acid, then, is simply achain of five-carbon sugars linked together by phosphodi-ester bonds with an organic base protruding from eachsugar (figure 3.14).

Two types of organic bases occur in nucleotides. Thefirst type, purines, are large, double-ring molecules found inboth DNA and RNA; they are adenine (A) and guanine(G). The second type, pyrimidines, are smaller, single-ringmolecules; they include cytosine (C, in both DNA andRNA), thymine (T, in DNA only), and uracil (U, in RNAonly).


Phosphate group

Sugar

Nitrogenous base

N

O

4

5

1

3 2

P CH2

O

–O

O–

OH ROH in RNA

H in DNA

O

FIGURE 3.13Structure of a nucleotide. The nucleotide subunits of DNA andRNA are made up of three elements: a five-carbon sugar, anorganic nitrogenous base, and a phosphate group.

5�

3�

P

P

P

P

OH

5-carbon sugar

Nitrogenous base

Phosphate group

Phosphodiesterbond

H C C

N C

HN

C

NH2 Adenine

H2N C C

N N

N

C

HN

C

C H

O

O

O

O

O

Guanine

H

N

NC H

O C C

N C

H

N

C

NH2 Cytosine(both DNAand RNA)

Thymine(DNA only)

Uracil(RNA only)

O C C

N C

H

N

C

O

H

H

H

CH3

H

O C C

N C

H

N

C

O

H H

H

PURINES

PYRIMIDINES

(a)

(b)

FIGURE 3.14The structure of a nucleic acid and the organic nitrogen-containing bases. (a) In a nucleic acid, nucleotides are linked to one anothervia phosphodiester bonds, with organic bases protruding from the chain. (b) The organic nitrogenous bases can be either purines orpyrimidines. In DNA, thymine replaces the uracil found in RNA.

DNA

Organisms encode the informationspecifying the amino acid sequencesof their proteins as sequences of nu-cleotides in the DNA. This methodof encoding information is very sim-ilar to that by which the sequencesof letters encode information in asentence. While a sentence writtenin English consists of a combinationof the 26 different letters of the al-phabet in a specific order, the codeof a DNA molecule consists of dif-ferent combinations of the fourtypes of nucleotides in specific se-quences such as CGCTTACG. Theinformation encoded in DNA is usedin the everyday metabolism of theorganism and is passed on to the or-ganism’s descendants.

DNA molecules in organisms ex-ist not as single chains folded intocomplex shapes, like proteins, butrather as double chains. Two DNApolymers wind around each otherlike the outside and inside rails of acircular staircase. Such a windingshape is called a helix, and a helixcomposed of two chains windingabout one another, as in DNA, iscalled a double helix. Each step ofDNA’s helical staircase is a base-pair, consisting of a base in onechain attracted by hydrogen bondsto a base opposite it on the otherchain. These hydrogen bonds holdthe two chains together as a duplex(figure 3.15). The base-pairing rulesare rigid: adenine can pair only withthymine (in DNA) or with uracil (inRNA), and cytosine can pair onlywith guanine. The bases that partici-pate in base-pairing are said to becomplementary to each other. Addi-tional details of the structure ofDNA and how it interacts with RNAin the production of proteins arepresented in chapters 14 and 15.

RNA

RNA is similar to DNA, but with two major chemicaldifferences. First, RNA molecules contain ribose sugarsin which the number 2 carbon is bonded to a hydroxylgroup. In DNA, this hydroxyl group is replaced by a hy-drogen atom. Second, RNA molecules utilize uracil in


O

OH

3� end

5� end

O

O

O

GC

P

O

O

O

O

O

O

O

P

P

P

P

P

P

P

P

P

C

C

G

G

A

A

T

T

Sugar-phosphate "backbone"

Hydrogen bonds betweennitrogenous bases

Phosphodiesterbond

FIGURE 3.15The structure of DNA. Hydrogen bond formation (dashed lines) between the organicbases, called base-pairing, causes the two chains of a DNA duplex to bind to each otherand form a double helix.

place of thymine. Uracil has the same structure as thy-mine, except that one of its carbons lacks a methyl (—CH3) group.

Transcribing the DNA message into a chemically differ-ent molecule such as RNA allows the cell to tell which isthe original information storage molecule and which is thetranscript. DNA molecules are always double-stranded (ex-cept for a few single-stranded DNA viruses that will be dis-cussed in chapter 33), while the RNA molecules tran-scribed from DNA are typically single-stranded (figure

3.16). Although there is no chemical reason why RNA can-not form double helices as DNA does, cells do not possessthe enzymes necessary to assemble double strands of RNA,as they do for DNA. Using two different molecules, onesingle-stranded and the other double-stranded, separatesthe role of DNA in storing hereditary information from therole of RNA in using this information to specify proteinstructure.

Which Came First, DNA or RNA?

The information necessary for the synthesis of proteins isstored in the cell’s double-stranded DNA base sequences.The cell uses this information by first making an RNAtranscript of it: RNA nucleotides pair with complementary

DNA nucleotides. By storing the information in DNA whileusing a complementary RNA sequence to actually directprotein synthesis, the cell does not expose the information-encoding DNA chain to the dangers of single-strand cleav-age every time the information is used. Therefore, DNA isthought to have evolved from RNA as a means of preserv-ing the genetic information, protecting it from the ongo-ing wear and tear associated with cellular activity. This ge-netic system has come down to us from the verybeginnings of life.

The cell uses the single-stranded, short-lived RNA tran-script to direct the synthesis of a protein with a specific se-quence of amino acids. Thus, the information flows fromDNA to RNA to protein, a process that has been termed the“central dogma” of molecular biology.

ATP

In addition to serving as subunits of DNA and RNA, nu-cleotide bases play other critical roles in the life of a cell.For example, adenine is a key component of the moleculeadenosine triphosphate (ATP; figure 3.17), the energy cur-rency of the cell. It also occurs in the molecules nicotina-mide adenine dinucleotide (NAD+) and flavin adenine dinu-cleotide (FAD+), which carry electrons whose energy is usedto make ATP.

A nucleic acid is a long chain of five-carbon sugars withan organic base protruding from each sugar. DNA is adouble-stranded helix that stores hereditaryinformation as a specific sequence of nucleotide bases.RNA is a single-stranded molecule that transcribes thisinformation to direct protein synthesis.


P

P

P

P

PP

P

P

P

PP

P

P

P

P

P

P

P

P

P

P

P

DNADeoxyribose-phosphate

backbone

Bases

Hydrogen bondingoccurs between base-pairs

RNA

Ribose-phosphatebackbone

Bases

G

C

G

G

G

C

C

T

A

A

A

A

A

A

T

TT

G

C

U

U

FIGURE 3.16DNA versus RNA. DNA forms a double helix, uses deoxyribose asthe sugar in its sugar-phosphate backbone, and utilizes thymineamong its nitrogenous bases. RNA, on the other hand, is usuallysingle-stranded, uses ribose as the sugar in its sugar-phosphatebackbone, and utilizes uracil in place of thymine.

Triphosphate group

5-carbon sugar

Nitrogenous base(adenine)

O

4

5

1

3 2

P CH2

O

O

O–

P

O

O

O–

P

O

–O

O–

OH OH

OO

NH2

N

N

N

N

FIGURE 3.17ATP. Adenosine triphosphate (ATP) contains adenine, a five-carbon sugar, and three phosphate groups. This molecule servesto transfer energy rather than store genetic information.

Lipids are a loosely defined group of molecules with onemain characteristic: they are insoluble in water. The mostfamiliar lipids are fats and oils. Lipids have a very high pro-portion of nonpolar carbon-hydrogen (C—H) bonds, and solong-chain lipids cannot fold up like a protein to sequestertheir nonpolar portions away from the surrounding aqueousenvironment. Instead, when placed in water many lipid mol-ecules will spontaneously cluster together and expose whatpolar groups they have to the surrounding water while se-questering the nonpolar parts of the molecules togetherwithin the cluster. This spontaneous assembly of lipids is ofparamount importance to cells, as it underlies the structureof cellular membranes.

Phospholipids Form MembranesPhospholipids are among the most important molecules ofthe cell, as they form the core of all biological membranes.An individual phospholipid is a composite molecule, madeup of three kinds of subunits:

1. Glycerol, a three-carbon alcohol, with each carbonbearing a hydroxyl group. Glycerol forms the back-bone of the phospholipid molecule.

2. Fatty acids, long chains of C—H bonds (hydrocarbonchains) ending in a carboxyl (—COOH) group. Twofatty acids are attached to the glycerol backbone in aphospholipid molecule.

3. Phosphate group, attached to one end of the glycerol.The charged phosphate group usually has a chargedorganic molecule linked to it, such as choline, etha-nolamine, or the amino acid serine.

The phospholipid molecule can be thought of as having apolar “head” at one end (the phosphate group) and twolong, very nonpolar “tails” at the other. In water, the non-polar tails of nearby phospholipids aggregate away from thewater, forming two layers of tails pointed toward each oth-er—a lipid bilayer (figure 3.18). Lipid bilayers are the basicframework of biological membranes, discussed in detail inchapter 6.

H|

H—C—Fatty acid|

H—C—Fatty acid|

H—C—Phosphate group|H

Because the C—H bonds in lipids are very nonpolar,they are not water-soluble, and aggregate together inwater. This kind of aggregation by phospholipids formsbiological membranes.



Hydrophobic"tails"

Hydrophilic"heads"

Hydrophobicregion

Hydrophilicregion

Hydrophilicregion

Oil

Water

Water

Water

(a)

(b)

FIGURE 3.18Phospholipids. (a) At an oil-water interface, phospholipid molecules will orient so that their polar (hydrophilic) heads are in the polarmedium, water, and their nonpolar (hydrophobic) tails are in the nonpolar medium, oil. (b) When surrounded by water, phospholipidmolecules arrange themselves into two layers with their heads extending outward and their tails inward.

Fats and Other Kinds of LipidsFats are another kind of lipid, but unlike phospholipids, fatmolecules do not have a polar end. Fats consist of a glycerolmolecule to which is attached three fatty acids, one to eachcarbon of the glycerol backbone. Because it contains threefatty acids, a fat molecule is called a triglyceride, or, moreproperly, a triacylglycerol (figure 3.19). The three fattyacids of a triglyceride need not be identical, and often theydiffer markedly from one another. Organisms store the en-ergy of certain molecules for long periods in the many C—H bonds of fats.

Because triglyceride molecules lack a polar end, they arenot soluble in water. Placed in water, they spontaneouslyclump together, forming fat globules that are very large rel-ative to the size of the individual molecules. Because fats areinsoluble, they can be deposited at specific locations withinan organism.

Storage fats are one kind of lipid. Oils such as olive oil,corn oil, and coconut oil are also lipids, as are waxes such asbeeswax and earwax (see table 3.1). The hydrocarbon chainsof fatty acids vary in length; the most common are even-numbered chains of 14 to 20 carbons. If all of the internalcarbon atoms in the fatty acid chains are bonded to at leasttwo hydrogen atoms, the fatty acid is said to be saturated,because it contains the maximum possible number of hydro-gen atoms (figure 3.20). If a fatty acid has double bonds be-

tween one or more pairs of successive carbon atoms, thefatty acid is said to be unsaturated. If a given fatty acid hasmore than one double bond, it is said to be polyunsaturat-ed. Fats made from polyunsaturated fatty acids have lowmelting points because their fatty acid chains bend at thedouble bonds, preventing the fat molecules from aligningclosely with one another. Consequently, a polyunsaturatedfat such as corn oil is usually liquid at room temperature andis called an oil. In contrast, most saturated fats such as thosein butter are solid at room temperature.

Organisms contain many other kinds of lipids besidesfats (see figure 3.19). Terpenes are long-chain lipids that arecomponents of many biologically important pigments, suchas chlorophyll and the visual pigment retinal. Rubber isalso a terpene. Steroids, another type of lipid found in mem-branes, are composed of four carbon rings. Most animalcell membranes contain the steroid cholesterol. Other ste-roids, such as testosterone and estrogen, function in multi-cellular organisms as hormones. Prostaglandins are a groupof about 20 lipids that are modified fatty acids, with twononpolar “tails” attached to a five-carbon ring. Prostaglan-dins act as local chemical messengers in many vertebratetissues.

Cells contain many kinds of molecules in addition tomembrane phospholipids that are not soluble in water.


(a) Phospholipid (phosphatidyl choline)

HO

(c) Terpene (citronellol)

(d) Steroid (cholesterol)

OP

O–

O

O

C

CH3 CH3 OH

CH3

CH3

CH

CH2

CH

CH2

CH2

(CH2)14 CH3

CH3

CO

(CH2)7 (CH2)7CH CHCO

CH2CH3

CH3

CH3

N+

H3C CH2

CH2

CH2

CH

CH3

CH3

CH2CH2

CH2

CH2

CH

CH2

CH2

O

O

H

H

CH O

CH O

CH O C

O

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

H

C

O

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

H

C

O

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

H

(b) Triacylglycerol molecule

FIGURE 3.19Lipids. These structures represent four major classes of biologically important lipids: (a) phospholipids, (b) triacylglycerols(triglycerides), (c) terpenes, and (d) steroids.

Fats as FoodMost fats contain over 40 carbon atoms. The ratio of energy-storing C—H bonds to carbon atoms in fats is more thantwice that of carbohydrates (see next section), making fatsmuch more efficient molecules for storing chemical energy.On the average, fats yield about 9 kilocalories (kcal) ofchemical energy per gram, as compared with somewhat lessthan 4 kcal per gram for carbohydrates.

All fats produced by animals are saturated (except somefish oils), while most plant fats are unsaturated. The excep-tions are the tropical oils (palm oil and coconut oil), whichare saturated despite their fluidity at room temperature. Itis possible to convert an oil into a solid fat by adding hy-drogen. Peanut butter sold in stores is usually artificiallyhydrogenated to make the peanut fats solidify, preventingthem from separating out as oils while the jar sits on thestore shelf. However, artificially hydrogenating unsaturat-ed fats seems to eliminate the health advantage they haveover saturated fats, as it makes both equally rich in C—H

bonds. Therefore, it now appears that margarine madefrom hydrogenated corn oil is no better for your healththan butter.

When an organism consumes excess carbohydrate, it isconverted into starch, glycogen, or fats and reserved for fu-ture use. The reason that many humans gain weight as theygrow older is that the amount of energy they need decreas-es with age, while their intake of food does not. Thus, anincreasing proportion of the carbohydrate they ingest isavailable to be converted into fat.

A diet rich in fats is one of several factors that arethought to contribute to heart disease, particularly to ath-erosclerosis, a condition in which deposits of fatty tissuecalled plaque adhere to the lining of blood vessels, blockingthe flow of blood. Fragments of plaque, breaking off from adeposit, are a major cause of strokes.

Fats are efficient energy-storage molecules because oftheir high concentration of C—H bonds.


O

C

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

HHO

H

C

H

C

H

H

C

H

H

O

C

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

H

C

H

C

H

H

C

H

C

H

C

H

H

C

H

C

H

C

H

CHO

No double bonds between carbon atoms; fatty acidchains fit close together

Double bonds present between carbon atoms; fatty acidchains do not fit close together

(a) Saturated fat

(b) Unsaturated fat

FIGURE 3.20Saturated and unsaturated fats. (a) Palmitic acid, with no double bonds and, thus, a maximum number of hydrogen atoms bonded to thecarbon chain, is a saturated fatty acid. Many animal triacylglycerols (fats) are saturated. Because their fatty acid chains can fit closelytogether, these triacylglycerols form immobile arrays called hard fat. (b) Linoleic acid, with three double bonds and, thus, fewer than themaximum number of hydrogen atoms bonded to the carbon chain, is an unsaturated fatty acid. Plant fats are typically unsaturated. Themany kinks the double bonds introduce into the fatty acid chains prevent the triacylglycerols from closely aligning and produce oils, whichare liquid at room temperature.

Simple CarbohydratesCarbohydrates function as energy-storage molecules as wellas structural elements. Some are small, simple molecules,while others form long polymers.

Sugars Are Simple Carbohydrates

The carbohydrates are a loosely defined group of mole-cules that contain carbon, hydrogen, and oxygen in themolar ratio 1:2:1. Their empirical formula (which lists theatoms in the molecule with subscripts to indicate how manythere are of each) is (CH2O)n, where n is the number of car-bon atoms. Because they contain many carbon-hydrogen(C—H) bonds, which release energy when they are broken,carbohydrates are well suited for energy storage.

Monosaccharides. The simplest of the carbohydratesare the simple sugars, or monosaccharides (Greek mono,“single” + Latin saccharum, “sugar”). Simple sugars maycontain as few as three carbon atoms, but those that playthe central role in energy storage have six (figure 3.21).The empirical formula of six-carbon sugars is:

C6H12O6, or (CH2O)6

Six-carbon sugars can exist in a straight-chain form, but inan aqueous environment they almost always form rings.The most important of these for energy storage is glucose(figure 3.22), a six-carbon sugar which has seven energy-storing C—H bonds.


3.5 Carbohydrates store energy and provide building materials.

4

5

1

3 2H H H

HHH

OH OH

OHO

4

4

4

4

5

5

5

5

666

1

1

1

1

3

3

2

233

2

2

OH H

OHO

CH2OH

CH 2OH

CH 2OH CH 2OH

OH

HO

O

OH

OHHO

CH2OH

H

H

HHO

H H

HH

OH

H

OH

OH

OH

O

H

H

HO

CH2OH

HH

H

OH

O

GalactoseFructoseGlucose

RiboseGlyceraldehyde

3-carbonsugar

5-carbon sugars

6-carbon sugars

Deoxyribose

HH

1

3

2

H

H

H

H

OH

OH

OC

C

C

FIGURE 3.21Monosaccharides. Monosaccharides, or simple sugars, cancontain as few as three carbon atoms and are often used asbuilding blocks to form larger molecules. The five-carbon sugarsribose and deoxyribose are components of nucleic acids (see figure3.15). The six-carbon sugar glucose is a component of largeenergy-storage molecules.

CH2OH

CH2OH

HO

H

H

C CC 3 24

OH

OHH

H

H

HOH

H

H

H

H

H

OH

O

HO

HO

HO

HO

C

H

1

O

HC56

H

C

H

H

H

HO

OH

HOOH

C

H

C CC

23

4

6

5

32 1

4

5

6

1

C H

HO

H

C C O

C

H

HH

OH

HO

H

OH

C

OH

H

23

4

5

6

1

HO

HO O

HO

C

H OH

OH

HC

H

34 1256

6 5

41

2

3

H

CH

H

O

FIGURE 3.22Structure of the glucose molecule. Glucose is a linear six-carbon molecule that forms a ring shape in solution. The structureof the ring can be represented in many ways; the ones shown hereare the most common, with the carbons conventionally numbered(in green) so that the forms can be compared easily. The bold,darker lines represent portions of the molecule that are projectingout of the page toward you—remember, these are three-dimensional molecules!

Disaccharides. Many familiar sugars like sucrose are“double sugars,” two monosaccharides joined by a covalentbond (figure 3.23). Called disaccharides, they often play arole in the transport of sugars, as we will discuss shortly.

Polysaccharides. Polysaccharides are macromoleculesmade up of monosaccharide subunits. Starch is a polysac-charide used by plants to store energy. It consists entirely ofglucose molecules, linked one after another in long chains.Cellulose is a polysaccharide that serves as a structuralbuilding material in plants. It too consists entirely of glucosemolecules linked together into chains, and special enzymesare required to break the links.

Sugar Isomers

Glucose is not the only sugar with the formula C6H12O6.Other common six-carbon sugars such as fructose and ga-lactose also have this same empirical formula (figure 3.24).These sugars are isomers, or alternative forms, of glucose.Even though isomers have the same empirical formula,their atoms are arranged in different ways; that is, theirthree-dimensional structures are different. These structuraldifferences often account for substantial functional differ-ences between the isomers. Glucose and fructose, for exam-ple, are structural isomers. In fructose, the double-bondedoxygen is attached to an internal carbon rather than to aterminal one. Your taste buds can tell the difference, asfructose tastes much sweeter than glucose, despite the factthat both sugars have the same chemical composition. Thisstructural difference also has an important chemical conse-quence: the two sugars form different polymers.

Unlike fructose, galactose has the same bond structure asglucose; the only difference between galactose and glucoseis the orientation of one hydroxyl group. Because the hy-droxyl group positions are mirror images of each other,

galactose and glucose are called stereoisomers. Again, thisseemingly slight difference has important consequences, asthis hydroxyl group is often involved in creating polymerswith distinct functions, such as starch (energy storage) andcellulose (structural support).

Sugars are among the most important energy-storagemolecules in organisms, containing many energy-storingC—H bonds. The structural differences among sugarisomers can confer substantial functional differencesupon the molecules.


Sucrose

CH2OH

CH2OH

OH

HO

OCH2OH

HO

OH

OH

O

O

Lactose

OH

OH

HO

CH2OH

H

H H

H

H

H

H

H

H

H

HH

H

OH

OH

OH

O

H

H

O

CH2OH

HH

HOH

O

Galactose

Glucose

Glucose Fructose

FIGURE 3.23Disaccharides. Sugars like sucrose and lactose are disaccharides,composed of two monosaccharides linked by a covalent bond.

C

———

OC ———O

——

—

H — C — OH

OH

—

H — C — OH

—

H

HO — C — H

C ——O

—

H — C — OH

—

H

Fructose

H — C — OH

——

—

H — C — OH

—

H — C — OH

—

H

HO — C — H

—

H — C — OH

—

H

Glucose

HO — C — H

——

—

H — C — OH

—

H — C — OH

—

H

HO — C — H

—

H — C — OH

—H

Galactose

Structuralisomer Stereoisomer

H — C —

FIGURE 3.24Isomers and stereoisomers. Glucose,fructose, and galactose are isomers with theempirical formula C6H12O6. A structuralisomer of glucose, such as fructose, hasidentical chemical groups bonded to differentcarbon atoms, while a stereoisomer of glucose,such as galactose, has identical chemical groupsbonded to the same carbon atoms but indifferent orientations.

Linking Sugars TogetherTransport Disaccharides

Most organisms transport sugars within their bodies. Inhumans, the glucose that circulates in the blood does so asa simple monosaccharide. In plants and many other or-ganisms, however, glucose is converted into a transportform before it is moved from place to place within the or-ganism. In such a form it is less readily metabolized (usedfor energy) during transport. Transport forms of sugarsare commonly made by linking two monosaccharides to-gether to form a disaccharide (Greek di, “two”). Disaccha-rides serve as effective reservoirs of glucose because thenormal glucose-utilizing enzymes of the organism cannotbreak the bond linking the two monosaccharide subunits.Enzymes that can do so are typically present only in thetissue where the glucose is to be used.

Transport forms differ depending on which monosac-charides link to form the disaccharide. Glucose formstransport disaccharides with itself and many other mono-saccharides, including fructose and galactose. When glu-cose forms a disaccharide with its structural isomer, fruc-tose, the resulting disaccharide is sucrose, or table sugar(figure 3.25a). Sucrose is the form in which most plantstransport glucose and the sugar that most humans (andother animals) eat. Sugarcane is rich in sucrose, and so aresugar beets.

When glucose is linked to its stereoisomer, galactose,the resulting disaccharide is lactose, or milk sugar. Manymammals supply energy to their young in the form of lac-tose. Adults have greatly reduced levels of lactase, the en-zyme required to cleave lactose into its two monosaccha-ride components, and thus cannot metabolize lactose asefficiently. Most of the energy that is channeled into lac-tose production is therefore reserved for their offspring.

Storage Polysaccharides

Organisms store the metabolic energy contained inmonosaccharides by converting them into disaccharides,such as maltose (figure 3.25b), which are then linked togeth-er into insoluble forms that are deposited in specific storageareas in their bodies. These insoluble polysaccharides arelong polymers of monosaccharides formed by dehydrationsynthesis. Plant polysaccharides formed from glucose arecalled starches. Plants store starch as granules within chlo-roplasts and other organelles. Because glucose is a key met-abolic fuel, the stored starch provides a reservoir of energyavailable for future needs. Energy for cellular work can beretrieved by hydrolyzing the links that bind the glucosesubunits together.

The starch with the simplest structure is amylose, whichis composed of many hundreds of glucose molecules linkedtogether in long, unbranched chains. Each linkage occursbetween the number 1 carbon of one glucose molecule andthe number 4 carbon of another, so that amylose is, in ef-fect, a longer form of maltose. The long chains of amylosetend to coil up in water (figure 3.26a), a property that ren-ders amylose insoluble. Potato starch is about 20% amy-lose. When amylose is digested by a sprouting potato plant(or by an animal that eats a potato), enzymes first break itinto fragments of random length, which are more solublebecause they are shorter. Baking or boiling potatoes has thesame effect, breaking the chains into fragments. Anotherenzyme then cuts these fragments into molecules of mal-tose. Finally, the maltose is cleaved into two glucose mole-cules, which cells are able to metabolize.

Most plant starch, including the remaining 80% of po-tato starch, is a somewhat more complicated variant ofamylose called amylopectin (figure 3.26b). Pectins arebranched polysaccharides. Amylopectin has short, linearamylose branches consisting of 20 to 30 glucose subunits.


CH2OH

Glucose

HO

OH

OH

OCH2OH

H2O

+

MaltoseGlucose

HO

OH

OHOH

OCH2OH

HO

OH

OH

OCH2OH

O

OH

OHOH

O

CH2OH

Glucose

HO

OH

OH

OH

OH

O

CH2OH

CH2OHH2O

+

SucroseFructose

HO

OH

HO

O

CH2OH

CH2OH

OH

HO

OCH2OH

HO

OH

OH

O

O

(a)

(b)

FIGURE 3.25How disaccharides form.Some disaccharides are usedto transport glucose from onepart of an organism’s body toanother; one example issucrose (a), which is found insugarcane. Otherdisaccharides, such as maltosein grain (b), are used forstorage.

In some plants these chains are cross-linked. The cross-links create an insol-uble mesh of glucose, which can be de-graded only by another kind ofenzyme. The size of the mesh differsfrom plant to plant; in rice about 100amylose chains, each with one or twocross-links, forms the mesh.

The animal version of starch is gly-cogen. Like amylopectin, glycogen is aninsoluble polysaccharide containingbranched amylose chains. In glycogen,the average chain length is muchgreater and there are more branchesthan in plant starch (figure 3.26c). Hu-mans and other vertebrates store ex-cess food energy as glycogen in the liv-er and in muscle cells; when thedemand for energy in a tissue increas-es, glycogen is hydrolyzed to releaseglucose.

Nonfattening Sweets

Imagine a kind of table sugar thatlooks, tastes, and cooks like the realthing, but has no calories or harmfulside effects. You could eat mountainsof candy made from such sweetenerswithout gaining weight. As Louis Pas-teur discovered in the late 1800s, mostsugars are “right-handed” molecules,in that the hydroxyl group that binds acritical carbon atom is on the rightside. However, “left-handed” sugars,in which the hydroxyl group is on theleft side, can be made readily in thelaboratory. These synthetic sugars aremirror-image chemical twins of thenatural form, but the enzymes thatbreak down sugars in the human di-gestive system can tell the difference.To digest a sugar molecule, an enzymemust first grasp it, much like a shoefitting onto a foot, and all of thebody’s enzymes are right-handed! Aleft-handed sugar doesn’t fit, any morethan a shoe for the right foot fits ontoa left foot.

The Latin word for “left” is levo, and left-handed sugarsare called levo-, or 1-sugars. They do not occur in natureexcept for trace amounts in red algae, snail eggs, and sea-weed. Because they pass through the body without beingused, they can let diet-conscious sweet-lovers have theircake and eat it, too. Nor will they contribute to toothdecay because bacteria cannot metabolize them, either.

Starches are glucose polymers. Most starches arebranched and some are cross-linked. The branchingand cross-linking render the polymer insoluble andprotect it from degradation.


(a) Amylose (b) Amylopectin

(c) Glycogen

FIGURE 3.26Storage polysaccharides. Starches are long glucose polymers that store energy in plants.(a) The simplest starches are long chains of maltose called amylose, which tend to coil upin water. (b) Most plants contain more complex starches called amylopectins, which arebranched. (c) Animals store glucose in glycogen, which is more extensively branched thanamylopectin and contains longer chains of amylose.

StructuralCarbohydratesWhile some chains of sugars store en-ergy, others serve as structural materialfor cells.

Cellulose

For two glucose molecules to link to-gether, the glucose subunits must bethe same form. Glucose can form aring in two ways, with the hydroxylgroup attached to the carbon where thering closes being locked into place ei-ther below or above the plane of thering. If below, it is called the alphaform, and if above, the beta form. Allof the glucose subunits of the starchchain are alpha-glucose. When a chainof glucose molecules consists of allbeta-glucose subunits, a polysaccharidewith very different properties results.This structural polysaccharide is cel-lulose, the chief component of plant cellwalls (figure 3.27). Cellulose is chemi-cally similar to amylose, with one im-portant difference: the starch-degradingenzymes that occur in most organismscannot break the bond between twobeta-glucose sugars. This is not becausethe bond is stronger, but rather be-cause its cleavage requires an enzymemost organisms lack. Because cellulosecannot be broken down readily, it works well as a biologicalstructural material and occurs widely in this role in plants.Those few animals able to break down cellulose find it arich source of energy. Certain vertebrates, such as cows, candigest cellulose by means of bacteria and protists they har-bor in their intestines which provide the necessary enzymes.

Chitin

The structural building material in insects, many fungi, andcertain other organisms is called chitin (figure 3.28). Chitinis a modified form of cellulose with a nitrogen group addedto the glucose units. When cross-linked by proteins, itforms a tough, resistant surface material that serves as thehard exoskeleton of arthropods such as insects and crusta-ceans (see chapter 46). Few organisms are able to digestchitin.

Structural carbohydrates are chains of sugars that arenot easily digested. They include cellulose in plants andchitin in arthropods and fungi.


FIGURE 3.27A journey into wood. This jumble of cellulosefibers (a) is from a yellow pine (Pinus ponderosa)(20×). (b) While starch chains consist of alpha-glucose subunits, (c) cellulose chains consist ofbeta-glucose subunits. Cellulose fibers can bevery strong and are quite resistant to metabolicbreakdown, which is one reason why wood is sucha good building material.

OH

CH2OH

α form of glucose Starch: chain of α-glucose subunits

HO

OH

OH HH

H H

H

OH

O

O O

O O

4 1 1

1

O

O O4

4

CH2OH

(b)

(c)

β form of glucose Cellulose: chain of β-glucose subunits

HO

OH

OH HH

H

H

H

O

OO

OO

OO

O

4 1

(a)

FIGURE 3.28Chitin. Chitin, which might be considered to be a modifiedform of cellulose, is the principal structural element in theexternal skeletons of many invertebrates, such as this lobster.

Chapter 3Summary Questions Media Resources


• The chemistry of living systems is the chemistry ofcarbon-containing compounds.

• Carbon’s unique chemical properties allow it to poly-merize into chains by dehydration synthesis, formingthe four key biological macromolecules: carbohy-drates, lipids, proteins, and nucleic acids.


1. What types of molecules areformed by dehydration reac-tions? What types of moleculesare formed by hydrolysis?

• Organic Chemistry

• Explorations: HowProteins Function

• Proteins

• Student Research: Anew Protein in Inserts

• Nucleic Acids

• Lipids

• Experiment:Anfinsen: Amino AcidSequence DeterminesProtein Shape

• Carbohydrates

2. How are amino acids linked toform proteins?3. Explain what is meant by theprimary, secondary, tertiary, andquaternary structure of a protein.

• Proteins are polymers of amino acids.• Because the 20 amino acids that occur in proteins

have side groups with different chemical properties,the function and shape of a protein are critically af-fected by its particular sequence of amino acids.


4. What are the three compo-nents of a nucleotide? How arenucleotides linked to form nucle-ic acids?5. Which of the purines and py-rimidines are capable of formingbase-pairs with each other?

• Hereditary information is stored as a sequence of nu-cleotides in a linear polymer called DNA, which ex-ists in cells as a double helix.

• Cells use the information in DNA by producing acomplementary single strand of RNA which directsthe synthesis of a protein whose amino acid sequencecorresponds to the nucleotide sequence of the DNAfrom which the RNA was transcribed.


6. What are the two kinds ofsubunits that make up a fat mole-cule, and how are they arrangedin the molecule?7. Describe the differences be-tween a saturated and an unsat-urated fat.

• Fats are one type of water-insoluble molecules calledlipids.

• Fats are molecules that contain many energy-richC—H bonds and, thus, provide an efficient form oflong-term energy storage.

• Types of lipids include phospholipids, fats, terpenes,steroids, and prostaglandins.


3.5 Carbohydrates store energy and provide building materials.

• Carbohydrates store considerable energy in theircarbon-hydrogen (C—H) bonds.

• The most metabolically important carbohydrate isglucose, a six-carbon sugar.

• Excess energy resources may be stored in complexsugar polymers called starches (in plants) and glyco-gen (in animals and fungi).

8. What does it mean to say thatglucose, fructose, and galactoseare isomers? Which two arestructural isomers, and how dothey differ from each other?Which two are stereoisomers,and how do they differ from eachother?

http://www.mhhe.com/raven6e http://www.biocourse.com

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