The Foundations of BiochemistryLevel 3:Level 4:Level 2:Level 1:SupramolecularThe cellMacromoleculesMonomericunitscomplexesand its organellesNucleotidesDNAChromatinAmino acidsProteinWPlasmamembraneCelluloseSugarsCellwallFIGURE1-11 Structural hierarchy in the molecular organization ofconsists of two types of macromolecules,DNA and many differentcells.The nucleus of this plant cell is an organelle containing severalproteins,eachmadeupof simplesubunits.types of supramolecular complexes, including chromatin.Chromatintypically1,000nmindiameter.Itisalong jumpfromsim-is dissolved or suspended in a gel-like cytosol with thou-ple biomolecules to cellular structures that can be seensands of otherproteins,some ofwhichbind tothat enl-with the light microscope.Figure l-ll illustrates thezyme and influence its activity. Some enzymes arestructural hierarchy in cellular organization.components of multienzyme complexes in which reac-The monomeric subunits ofproteins,nucleic acidstants arechanneled from one enzyme to another,neverand polysaccharides are joined by covalent bonds. Inentering the bulk solvent.Diffusion is hindered in thesupramolecularcomplexes,however,macromoleculesgel-like cytosol,and the cytosolic composition variesareheld togetherby noncovalentinteractions-muchthroughout the cell. In short, a given molecule may be-weaker, individually, than covalent bonds. Among thesehave quitedifferently in the cell and in vitro.Acentralnoncovalent interactions arehydrogen bonds (betweenchallenge of biochemistry is to understand the influencespolar groups), ionic interactions (between chargedof cellularorganizationandmacromolecularassociationsgroups),hydrophobic interactions (among nonpolaron thefunction of individual enzymes and otherbiomol-groups in aqueous solution),and van der Waals interac-ecules-to understandfunction in vivoas well as invitrotions(Londonforces)--all ofwhichhaveenergiesmuchsmaller than those of covalent bonds.These noncova-SUMMARY1.1CellularFoundationslent interactions are described in Chapter 2. The largeAll cells areboundedbyaplasmamembrane;numbersofweakinteractionsbetweenmacromoleculesin supramolecular complexes stabilizetheseassemblies,have acytosol containing metabolites, coenzymes,inorganic ions,and enzymes;and have a set ofproducingtheirunique structures.genes containedwithin a nucleoid (bacteriaandarchaea)ornucleus(eukaryotes)In Vitro Studies May Overlook Important Interactionsamong MoleculesPhototrophs use sunlight to do work; chemotrophsoxidizefuels,passingelectronstogood electronOne approach to understanding a biological process is toacceptors:inorganiccompounds,organicstudypurifiedmolecules invitro ("inglass"--inthetestcompounds,ormolecularoxygen.tube),without interference from other molecules pres-Bacterial and archaeal cells contain cytosol, aent in the intact cell-that is, in vivo ("in the living"). Al-nucleoid, andplasmids.Eukaryotic cells haveathough this approach has been remarkably revealing,wenucleus andaremulticompartmented,with certainmustkeep in mind that the inside of a cellis quite differprocesses segregated in specific organelles;ent from the inside of a test tube.The"interfering"com-organelles canbeseparatedand studiedinisolation.ponents eliminated by purification may be critical to thebiological functionorregulation of themoleculepurified.CytoskeletalproteinsassembleintolongfilamentsForexample,in vitro studies of pure enzymes are com-that give cells shape and rigidity and serve as railsmonly done at very low enzyme concentrations in thor-along which cellular organelles move throughoutOughly stirred aqueous solutions.Inthe cell,an enzymethe cell
Level 4: The cell and ite organelles FIGURE 1-11 Structural hierarchy in the molecular organization of cells. The nucleus of this plant cell is an organelle containing several types of supramolecular complexes, including chromatin. Chromatin typically 1,000 nm in diameter. It is a long jump from simple biomolecules to cellular structures that can be seen with the light microscope. Figure 1-11 illustrates the structural hierarchy in cellular organization. The monomeric subunits of proteins, nucleic acids, and polysaccharides are joined by covalent bonds. In supramolecular complexes, however, macromolecules are held together by noncovalent interactions-much weaker, individually, than covalent bonds. Among these noncovalent interactions are hydrogen bonds (between polar groups), ionic interactions (between charged groups), hydrophobic interactions (among nonpolar groups in aqueous solution), and van der Waals interactions (London forces)-all of which have energies much smaller than those of covalent bonds. These noncovalent interactions are described in Chapter 2. The large numbers of weak interactions between macromolecules in supramolecular complexes stabilize these assemblies, producing their unique structures. In Vitro Studies May Overlook lmportant Interactions among Molecules One approach to understandlng a biological process is to study puri-fled molecules in vitro ("in glass"-in the test tube), without interference from other molecules present in the intact cell-that is, in vivo ("in the living'). A1- though this approach has been remarkably revealing, we must keep in mind that the inside of a cell is quite different from the inside of a test tube. The "interfering" components eliminated by puriflcation may be critical to the biological function or regulation of the molecule purified. For example, in vitro studies of pure erzyrnes are commonly done at very low enzyme concentrations in thoroughly stirred aqueous solutions. In the cell, an enz).Tne Level 3: Level 2: Level 1: Supranolecular Macromoleculee Monomericunits complexes sugars *W+ consists of two types of macromolecules, DNA and many different proteins, each made up of simple subunits. is dissolved or suspended in a gel-like cytosol with thousands of other proteins, some of which bind to that enz5rme and influence its activity. Some enz}nnes are components of multienzyme complexes in which reactants are channeled from one enzyrne to another, never entering the bulk solvent. Diffusion is hindered in the gel-like cytosol, and the cytosolic composition varies throughout the cell. In short, a $ven molecule may behave quite differently in the cell and in vitro. A central challenge of biochemistry is to understand the ffiuences of cellular organization and macromolecular associations on the function of individual enzymes and other biomolecules-to understand function in vivo as well as in vitro. SUMMARY 1.1 Cellular Foundations r All cells are bounded by a plasma membrane; have a cytosol containing metabolites, coenzymes, inorganic ions, and enzymes; and have a set of genes contained within a nucleoid (bacteria and archaea) or nucleus (eukaryotes). r Phototrophs use sunlight to do work; chemotrophs oxidize fuels, passing electrons to good electron acceptors: inorganic compounds, organic compounds, or molecular oxygen. r Bacterial and archaeal cells contain cltosol, a nucleoid, and plasmids. Eukaryotic cells have a nucleus and are multicompartmented, with certain processes segregated in specific organelles; organelles can be separated and studied in isolation. r Cytoskeletal proteins assemble into long filaments that give cells shape and rigidity and serve as rails along which cellular organelles move throughout the cell
1.2 Chemical FoundationsFIGURE1-12 Elements essential to animal lifeHHand health.Bulk elements (shaded orange)areBulkelementsstructural components ofcellsandtissuesandareLiTraceelementsBrequired in the diet in gram quantities daily.Fortrace elements (shaded bright yellow), the re-1quirements are much smaller: for humans, a few1RmilligramsperdayofFe,Cu,andZn,evenlessofAthe others.The elemental requirementsforplantsOMRKMPand microorganisms are similar to those shownhere; the ways in which they acquirethese ele-2eteR1ments vary.OtnandeRActinidesSupramolecular complexes are held together byevolutionary origin is based in part on this observed uni-noncovalent interactions and form a hierarchy ofversalityofchemicalinternediatesandtransformations,structures,somevisiblewith thelight microscope.often termed"biochemicalunity."Whenindividual moleculesareremovedfrom theseFewer than 30of the more than 90naturallyoccur-ring chemical elements are essential to organisms.Mostcomplexesto be studied in vitro,interactionsofthe elements inlivingmatter have relativelylowatomicimportant in the living cell may be lost.numbers; onlytwohaveatomic numbersabovethat of se-lenium, 34 (Fig.1-12).Thefourmost abundant ele-mentsin living organisms,interms of percentage oftotal1.2ChemicalFoundationsnumber of atoms, are hydrogen, oxygen, nitrogen,andBiochemistry aims to explain biological form and functioncarbon,which together make up morethan 99% of theinchemicalterms.Bythelateeighteenthcentury,chemistsmass ofmost cells.Theyare the lightest elements capablehad concluded that the composition of living matter isofefficiently forming one, two,three,andfour bonds,re-strikingly different from that of the inanimate world.An-spectively; in general, the lightest elements form thetoine-Laurent Lavoisier (1743-1794)noted the relativestrongest bonds. The trace elements (Fig. 1-12) repre-chemical simplicity of the"mineral world"and contrastedsentaminisculefraction of theweight of thehuman body,it withthe complexity of the"plant and animal worlds";thebut all are essential to life, usually because they are es-latter,heknew,werecomposedofcompoundsrichintheel-sential to the function of specific proteins, includingenentscarbon,oxygen,nitrogen,andphosphorusmany enzymes.The oxygen-transporting capacity of theDuring thefirst half of thetwentieth century,paralhemoglobin molecule,for example, is absolutely dependlelbiochemical investigations ofglucosebreakdowninenton four iron ions thatmake up only0.3%of its mass.yeast and in animal muscle cells revealed remarkablechemical similarities in thesetwo apparentlyvery differBiomolecules Are Compounds ofCarbon witha Varietyofent cell types; the breakdown of glucose in yeast andFunctional Groupsmuscle cells involved the same 10 chemical intermedi-The chemistry of living organisms is organized aroundates,and the same 10 enzymes.Subsequent studies ofcarbon, which accounts for more than half the drymany otherbiochemical processes in many different or-weight of cells.Carbon can form single bonds with hy-ganisms have confirmed thegenerality of this observa-drogen atoms,and both singleand doublebonds withtion, neatly summarized in 1954 by Jacques Monod:"What is true of E. coli is true of the elephant." The curoxygenandnitrogen atoms(Fig.1-13).Ofgreatest significanceinbiologyistheabilityof carbonatomstoformrent understanding that all organisms share a commonC+HCHHC+NCNC-N-0.+0:0.0.0+00℃.0-FIGURE1-13 Versatilityof carbon.c.+.c...cC+-0:C::0:-0bonding.Carbon canform covalentsingle, double,and triple bonds (allbonds in red), particularly with other0+℃-C.+N:-+CiN:-C-C-00.carbon atoms.Triple bonds are rareinbiomolecules
@ Bulk elements F- Trace elements 3 Li Be 6 B 9 F 10 Ne L2 Mg t3 AI 14 st 'lo I 18 Ar 21 9c 22 Ti 2A v 24 Cr 26 It[D 26 Fe 27 Co 2a Ni 29 Cu 30 Za Ge 32 G€ 33 Ag u ll€ Br 36 Kr g 7 Rb a8 Sr 39 Y 40 Zt 4 1 Nb 42 Mo 43 Tc Ru t6 nh 46 Pd t7 AS 48 cd l9 In t0 Sn sb 52 Te I 64 Xe t6 C e i6 Ba R 72 Hf Ta w Re 76 Oe 71 Ir r E Pt 79 Au t0 Hg l 1 TI ,2 Pb 83 Bi 84 Po 86 At Rn 87 Fr t5 Ra Lanthanides Actinides r Supramolecular complexes are held together by noncovalent interactions and form a hierarchy of structures, some visible with the light microscope. When individual molecules are removed from these complexes to be studied in vitro, interactions important in the living cell may be lost. 1.2 Chemical Foundations Biochemistry aims to explain biological form and function in chemical terms. By the late eighteenth century, chemists had concluded that the composition of living matter is strikrgly djfferent from that of the inanimate world. Antoine-Laurent Lavoisier (1743-1794) noted the relative chemical simplicity of the "mineral world" and contrasted it with the complexity of the "plant and animal worlds"; the Iatter, he lcrew, were composed of compolnds rich in the elements carbon, oxygen, nitrogen, and phosphorus. During the flrst half of the twentieth century paralIel biochemical investigations of glucose breakdown in yeast and in animal muscle cells revealed remarkable chemical similarities in these two apparently very different cell types; the breakdown of glucose in yeast and muscle celis nvolved the same 10 chemical intermediates, and the same 10 enzl'rnes. Subsequent studies of many other biochemical processes in many different organisms have confirmed the generality of this observation, neatly summarized in 1954 by Jacques Monod: "What is true of E. co\i, is true of the elephant." The current understanding that all organisms share a common FIGURE 1-12 Elements essential to animal life and health. Bulk elements (shaded orange) are structural components of cells and tissues and are required in the diet in gram quantities daily. For trace elements (shaded bright yellow), the requirements are much smaller: for humans, a few milligrams per day of Fe, Cu, and Zn, even less of the others. The elemental requirements for plants and microorganisms are similar to those shown here; the ways in which they acquire these elements vary. evolutionary origin is based in part on this observed universality of chemical intermediates and transformations, often termed "biochemical unity." Fewer than 30 of the more than 90 naturally occurring chemical elements are essential to organisms. Most of the elements in living matter have relatively low atomic mrmbers; only two have atomic mrmbers above that of selenium, 34 (FiS. l-12). The four most abundant elements in livrng organisms, in terms of percentage of total number of atoms, are hydrogen, oxygen, nitrogen, and carbon, which together make up more than 99%o of the mass of most cells. They are the lightest elements capable of efflciently forming one, two, three, and four bonds, respectively; in general, the lightest elements form the strongest bonds. The trace elements (FiS. 1-12) represent a miniscule fraction of the weight of the human body, but all are essential to life, usually because they are essential to the function of specific proteins, including many enz)./rnes. The o)rygen-transporting capacity of the hemoglobin molecule, for example, is absolutely dependent on four iron ions that make up only 0.3% of its mass. Biomolecules Are Compounds of (arhon with a Variety of Functional Groups The chemistry of living organisms is organized around carbon, which accounts for more than half the dry weight of cells. Carbon can form single bonds with hydrogen atoms, and both single and double bonds with oxygen and nitrogen atoms (Fig. 1-13). Of greatest significance in biology is the ability of carbon atoms to form FIGURE 1-13 Versatility of carbon bonding. Carbon can form covalent single, double, and triple bonds (all bonds in red), particularly with other carbon atoms. Triple bonds are rare in biomolecules. .C + H -'9,t 'C'+.O: -+'C:O. I +.O: -) C::Q. C + N: +.C:N: I -CH I C:Ntl -C-Ct1 C-C -C:CI -c-ol C:O I -C-N I
12The Foundations of Biochemistry(a)(b)(c)120109.5109.5°BFIGURE1-14Geometryof carbonbonding.(a)Carbon atoms haveafor the compound ethane (CHg--CHs). (c)Double bonds are shortercharacteristic tetrahedral arrangement of their four single bonds.and do not allow free rotation. The two doubly bonded carbons and(b) Carbon-carbon singlebonds have freedomof rotation, as shownthe atoms designated A, B, X, andYall lie in the samerigid plane.HHHR-C-HRO-R?MethylEtherR-N-C-NGuanidiniumHAHHHHR'-C-O-R2EthylR--HEsterR-C-CHImidazole。HNHHHYHPhenylR-R-0-C-HR-S-HHAcetylSulfhydrylOHHHCarbonylR-C-HRI-C-0-C-R2AnhydrideR-SS-R2Disulfide(aldehyde)(twocar0Oboxylic acids)HR'-CR2CarbonylRIC-S-R?R-N-HAminoThioesterJ(ketone)(protonated)8HO"HR-C-0CarboxylAmidoR-CPhosphorylR-O-P-OH0H6OHOOINR-0-HRIC-R2HydroxylImineOR2Phosphoanhydride R'_O-(alcohol)CCO-HHORaEnolR-C=0N-SubstitutedR-CP-OHMixed anhydride-0Nimine (SchiffH(carboxylicacidandH0base)phosphoric acid;R-C-R?also called acylphosphate)FIGURE1-15 Some common functional groups ofbiomolecules.Incarbon-containing group.When two ormore substituents are shown inthis figure and throughout the book,we use R to represent"any sub-a molecule, we designate them R', R2, and so forth.stituent." It may be as simpie as a hydrogen atom, but typically it is a
FIGURE 1 - 14 Geometry of carbon bonding. (a) Carbon atoms have a characteristic tetrahedral arrangement of their four single bonds. (b) Carbon-carbon single bonds have freedom of rotation, as snown for the compound ethane (CH3-CH3). (c) Double bonds are shorter and do not allow free rotation. The two doubly bonded carbons and the atoms designated A, B, X, and Y all lie in the same rigid plane. Guanidinium T .,H R-N-C-N il\ )ft, H H H Methyl Ethyl Phenyl H I R-C-H I H H H 1l R-C-C-H H H H H Ether Ester Amido lmine R1-o-R2 Rl-c-o-R2 o Imidazole R-C:CH / \ ^'r'*' I H Enol N-Substituted imine (Schiff base) Rl FIGURE 1-15 Some common functional groups of biomolecules. In this figure and throughouthe book, we use R to represent ,any substituent." ltmay be as simple as a hydrogen atom, but typically it is a ?-",' R-C:CT\ Sulfhydryl R-S-H Disulfrde R1-S-S_R2 Thioester Rl-C-S-R2 o Phosphoryl Phosphoanhydride R' Mixed anhydride (carboxylic acid and phosphoric acid; also called acyl phosphate) R carbon-containing group. When two or more substituents are shown in a molecule, we designate them R], R2, and so forth. H H Carbonyl R-q-H (aldehyde) d Carbonyl Rt-9-R' (ketone) d Carboxyl Hydroxyl R-O-H (alcohol) T Acetyl R-O-Q-C-H ill O H Anhvdride -tl R1-C-O-C-R2 (two,car- ., d O ooxyllc acros, H I Amino R-N1-H I (protonated) 'l R-C-Oo H ,/ *-?-Nt' dH
1.2Chemical Foundationsverystablesinglebondswithuptofourothercarbonchemical"personality"of a compound isdetermined byatoms.Two carbon atoms also can share two (or three)the chemistry of its functional groups and their disposi-electron pairs,thus forming double (or triple) bonds.tion in three-dimensional space.Thefour singlebonds that canbeformed bya car-bon atom project from the nucleus to thefour apices ofCells Contain a Universal Set of Small Moleculesa tetrahedron (Fig.1-14),withanangleofabout 109.5between any two bonds and an average bond length ofDissolved in the aqueous phase (cytosol) ofall cells is a0.154 nm.Thereis free rotation around each singlecollection of perhaps a thousand different small organicbond, unless very large or highly charged groups are at-molecules(M,~100to~500),thecentralmetabolitestachedtobothcarbonatoms,in whichcaserotationmayin themajorpathways occurring innearlyevery cell-berestricted.Adoublebondis shorter (about 0.134nm)themetabolites and pathways thathavebeenconservedandrigid and allows only limited rotation about its axis.throughout the course of evolution. (See Box 1-1 for anCovalentlylinked carbon atoms inbiomolecules canexplanation ofthevarious ways ofreferring tomolecularform linear chains, branched chains,and cyclic strucweight.)This collection of molecules includes the com-tures. It seems likelythat thebonding versatility of car-mon amino acids,nucleotides, sugars and their phos-bon,with itself and with other elements,was amajorphorylated derivatives,andmono-,di-,and tricarboxylicfactor in the selection of carbon compoundsforthemo-acids.The molecules are polar or charged, water solu-lecular machinery of cells during the origin and evolu-ble,andpresentinmicromolartomillimolarconcentration of living organisms.No other chemical element cantions, They are trapped in the cell because the plasmaform molecules of such widely different sizes, shapes,membraneisimpermeabletothem--althoughspecificandcomposition.membrane transporters can catalyze the novement ofMostbiomolecules can beregarded as derivatives ofsomemoleculesintoandoutofthecellorbetweencomhydrocarbons,withhydrogen atoms replaced byavari-partments in eukaryotic cells.The universal occurrenceety of functional groups that confer specific chemicalof thesaneset ofcompounds in living cellsreflectstheevolutionary conservation of metabolic pathways thatproperties on the molecule, forming various families oforganiccompounds.Typicalofthesearealcohols,whichdeveloped in the earliest cells.There are other small biomolecules, specific tohave oneormorehydroxyl groups;amines,with aminocertain types of cells or organisms. For example, vascu-groups; aldehydes and ketones, with carbonyl groups;lar plants contain, in addition to the universal setand carboxylic acids,with carboxylgroups(Fig.1-15)Manybiomolecules are polyfunctional,containingtwosmall molecules called secondary metabolites,whichplay roles specific to plant life.These metabolites in-ormoretypes of functionalgroups(Fig.1-16),eachclude compounds that give plants their characteristicwith its own chemical characteristics and reactions.TheaminoNHimidazole-likephoaphoanhydride0HCHa0thioesteramidoamidoHOHCHa-C-S-CH-CH-NH-C-CH-CH2-NH-CCH2-HO0oOHCHaOOHOhydroxylOHO-P-0phosphorylOHAcetyl-coenzymeAFIGURE1-16Severalcommonfunctional groups in a single biomolecule.tional groups can exist in protonated or unprotonated forms, dependingAcetyl-coenzyme A (often abbreviated as acetyl-CoA) is a carrier of acetylon the pH. In the space-filling model, N is blue, C is black, Pis orange,Oisred,and H iswhite.Theyellowatomattheleftisthesulfurofthecritgroups in someenzymatic reactions.Thefunctional groups are screened inthe structural formula. As we will see in Chapter 2, several of these func-ical thioester bond between the acetyl moiety and coenzyme A
very stable single bonds with up to four other carbon atoms. Tlvo carbon atoms also can share two (or three) electron pairs, thus forming double (or triple) bonds. The four single bonds that can be formed by a carbon atom project from the nucleus to the four apices of a tetrahedron (Fig. l- I4), with an angle of about 109.5" between any two bonds and an average bond length of 0.154 nm. There is free rotation around each single bond, unless very large or highly charged groups are attached to both carbon atoms, in which case rotation may be restricted. A double bond is shorter (about 0.134 nm) and rigid and allows only limited rotation about its axis. Covalently linked carbon atoms in biomolecules can form Iinear chains, branched chains, and cyclic structures. It seems likely that the bonding versatility of carbon, with itself and with other elements, was a major factor in the selection of carbon compounds for the molecular machinery of cells during the origin and evolution of living organisms. No other chemical element can form molecules of such widely different sizes, shapes, and composition. Most biomolecules can be regarded as derivatives of hydrocarbons, with hydrogen atoms replaced by a variety of functional groups that confer speci_fichemical properties on the molecule, forming various families of organic compounds. Tlrpical of these are alcohols, which have one or more hydroxyl groups; amines, with amino groups; aldehydes and ketones, with carbonyl groups; and carboxylic acids, with carboxyl groups (Fig. 1-f 5). Many biomolecules are polyfunctional, containing two or more types of functional groups (FiS. 1-16), each with its own chemical characteristics and reactions. The FIGURE 1 - 16 Several common functional groups in a single biomolecule. Acetyl-coenzyme A(often abbreviated as acetyl-CoA) is a canier of acetyl groups in some enzymatic reactions. The functional groups are screened in the structural formula. As we will see in Chaoter 2. several of these funcchemical "personality" of a compound is determined by the chemistry of its functional groups and their disposition in three-dimensional space. Cells Contain a Universal Set of Small Molecules Dissolved in the aqueous phase (cytosol) of all cells is a collection of perhaps a thousand different small organic molecules (M, -100 to -500), the central metabolites in the major pathways occurring in nearly every cellthe metabolites and pathways that have been conserved throughout the course of evolution. (See Box 1-1 for an explanation of the various ways of referring to molecular weight.) This collection of molecules includes the common amino acids, nucleotides, sugars and their phosphorylated derivatives, and mono-, di-, and tricarboxylic acids. The molecules are polar or charged, water soluble, and present in micromolar to millimolar concentrations. They are trapped in the cell because the plasma membrane is impermeable to them-although specific membrane transporters can catalyze the movement of some molecules into and out of the cell or between compartments in eukaryotic cells. The universal occurrence of the same set of compounds in living cells reflects the evolutionary conservation of metabolic pathways that developed in the earliest cells. There are other small biomolecules, specific to certain types of cells or organisms. For example, vascular plants contain, in addition to the universal set, small molecules called secondary metabolites, which play roles speci.fic to plant life. These metabolites include compounds that give plants their characteristic Acetyl-coenzyme A tional groups can exist in protonated or unprotonated forms, depending on the pH. In the space-filling model, N is blue, C is black, P is orange, O is red, and H is white. The yellow atom at the left is the sulfur of the critical thioester bond between the acetyl moiety and coenzyme A
14TheFoundations of BiochemistryBox1-1MolecutarWeight,MolecularMass,andTheirCorrectUnitsTherearetwocommon (and equivalent)waystode-Consider, for example, a molecule with a mass 1,000scribe molecular mass: both are used in this text. Thetimes that of water.We can say of this molecule eitherfirst is molecular weight, or relative molecular mass,M,=18,000 or m =18,000 daltons.Wecan also dedenoted Mr.The molecular weight of a substance is describe it as an"18 kDa molecule."However, the expres-fined as the ratio of the mass of a molecule of that sub-sionM,=18,000 daltons isincorrect.stanceto one-twelfth the massofcarbon-12(12C).SinceAnother convenient unit for describing the mass ofMis a ratio, it is dimensionless-it has no associateda single atom or molecule is the atomic mass unit (for-units.The second is molecular mass, denoted m.Thismerly amu, now commonly denoted u).One atomicissimplythemass ofonemolecule,or themolarmassdi-mass unit (l u)isdefined as one-twelfth themass ofanvided by Avogadro's number.The molecularmass,m,isatom of carbon-12.Since the experimentally measuredexpressed in daltons (abbreviated Da).One dalton ismass ofan atom of carbon-12 is 1.9926x 10-23g,1u =equivalent to one-twelfth the mass of carbon-12; a kilo-1.6606 × 10-24 g. The atomic mass unit is convenientdalton (kDa) is 1,000 daltons; a megadalton (MDa) isfor describing the mass of a peak observed by massImilliondaltons.spectrometry (seeBox3-2).such as ribosomes. Table 1-1 shows the major classesscents, and compounds such as morphine,quinine,nico-tine,and caffeine that are valued for their physiolog-ofbiomoleculesinanE.colicell.ical effects on humans but used for other purposesProteins,long polymers of amino acids, constituteby plants.thelargestfraction (besides water)of a cell.Somepro-The entire collection of small molecules in a giventeins have catalytic activity and function as enzymes;cell has been called that cell's metabolome, in parallelothers serveasstructural elements,signalreceptors,orwith the term"genome" (defined earlier and expandedtransporters that carry specific substances into or out ofon in Section 1.5).cells.Proteins are perhaps the most versatile of all bio-molecules; a catalog of their many functions would beMacromolecules Are the Major Constituents of Cellsvery long.The sum of all the proteins functioning in aMany biological molecules aremacromolecules,poly-given cell is the cell's proteome. The nucleic acidsDNAand RNA,are polymers of nucleotides.They storemers with molecular weights above ~5,000 that areas-andtransmitgeneticinformation,and someRNAmole-sembled from relatively simple precursors.Shortercules have structural and catalytic roles in supramolec-polymers are called oligomers (Greek oligos, "few").Proteins,nucleicacids,and polysaccharides aremacro-ular complexes. The polysaccharides,polymers ofmolecules composed of monomers with molecularsimple sugars such as glucose, have three major funcweights of 500 orless.Synthesis of macromolecules isations: as energy-richfuel stores, as rigid structural com-ponents of cell walls (inplants and bacteria),and asmajor energy-consuming activity of cells.Macromole-cules themselves may be further assembled intoextracellular recognition elements that bind to proteinssupramolecular complexes,formingfunctional unitson othercells.Shorter polymers of sugars(oligosaccha-rides) attached to proteins or lipids at the cell surfaceserve as specific cellular signals. The lipids, water-TABLE1-1MolecularComponents ofan E.coli Cellinsoluble hydrocarbon derivatives, serve as structuralcomponents of membranes,energy-rich fuel stores,pig-Approximatenumber ofments,andintracellularsignals.Percentage ofdifferentProteins, polynucleotides, and polysaccharides havetotal weightmolecularlargenumbers of monomeric subunits and thus highof cellspeciesmolecular weights—in the range of 5,000 to more than1 millionforproteins,upto several billionfornucleicWater701acids,and in themillions forpolysaccharides such asProteins153,000starch. Individual lipid molecules are much smaller (M,Nucleic acids750 to 1,500) and are not classified as macromolecules.DNA11-4But they can associate noncovalently into very largeRNA6>3,000structures.Cellularmembranes are built of enormous3Polysaccharides10noncovalent aggregates of lipidand proteinmolecules.2Lipids20Given their characteristic information-rich subunitMonomeric subunitssequences,proteinsand nucleicacidsareoftenreferred2500andintermediatesto as informational macromolecules. Some oligosac-1Inorganic ions20charides, as noted above, also serve as informationalmolecules
There are two common (and equivalent) ways to describe molecular mass; both are used in this text. The first is molecular we'ight, or relatiue rnolecular rrutss, denoted M,. The molecular weight of a substance is defined as the ratio of the mass of a molecule of that substance to one-twelfth the mass of carbon-12 112C1. Since M, is a ratio, it is dimensionless-it has no associated units. The second is molecular ntnss, denoted rn. This is simply the mass of one molecule, or the molar mass divided by Avogadro's number. The molecular mass, rz, is expressed in daltons (abbreviated Da). One dalton is equivalent to one-twelfth the mass of carbon-l2; a kilodalton (kDa) is 1,000 daltons; a megadalton (MDa) is 1 million daltons. Consider, for example, a molecule with a mass 1,000 times that of water. We can say of this molecule either M. = 18,000 or m : 18,000 daltons. We can also describe it as an "18 kDa molecule." However, the expressionM, : 18,000 daltons is incorrect. Another convenient unit for describing the mass of a single atom or molecule is the atomic mass unit (formerly amu, now commonly denoted u). One atomic mass unit (l u) is defined as one-twelfth the mass of an atom of carbon-l2. Since the experimentally measured mass of an atom of carbon-l2 is 1.9926 x 10-23 g, 1 u : 1.6606 x 70-24 g. The atomic mass unit is convenient for describing the mass of a peak observed by mass spectrometry (see Box 3-2). scents, and compounds such as morphine, quinine, nicotine, and caffeine that are valued for their physiological effects on humans but used for other purposes by plants. The entire collection of small molecules in a given cell has been called that cell's metabolome, in parallel with the term "genome" (defined earlier and expanded on in Section 1.5). Macromolecules Are the Major (onstituents of Cells Many biological molecules are maeromolecules, polymers with molecular weights above -5,000 that are assembled from relatively simple precursors. Shorter pol;.'rners are called oligomers (Greek oligos, "few"). Proteins, nucleic acids, and polysaccharides are macromolecules composed of monomers with molecular weights of 500 or less. Synthesis of macromolecules is a major energy-consuming activity of cells. Macromolecules themselves may be further assembled into supramolecular complexes, forming functional units Pereentage of total weight of eell Approximate number of different molecular species such as ribosomes. Table 1-1 shows the major classes of biomolecules in an E'. coLi, cdl. Proteins, long polymers of amino acids, constitute the largest fraction (besides water) of a cell. Some proteins have catalytic activity and function as enzymes; others serve as structural elements, signal receptors, or transporters that carry speci-flc substances into or out of cells. Proteins are perhaps the most versatile of all biomolecules; a catalog of their many functions would be very long. The sum of all the proteins functioning in a given cell is the cell's proteome. The nueleie aeids, DNA and RNA, are polS.nners of nucleotides. They store and transmit genetic information, and some RNA molecules have structural and catalytic roles in supramolecular complexes. The polysaecharides, polymers of simple sugars such as glucose, have three major functions: as energy-rich fuel stores, as rigid structural components of cell walls (in plants and bacteria), and as extracellular recognition elements that bind to proteins on other cells. Shorter pol;rmers of sugars (oligosaccharides) attached to proteins or lipids at the cell surface serve as specific cellular signals. The lipids, waterinsoluble hydrocarbon derivatives, serve as structural components of membranes, energy-rich fuel stores, pigments, and intracellular signals. Proteins, polynucleotides, and polysaccharides have Iarge numbers of monomeric subunits and thus high molecular weights-in the range of 5,000 to more than 1 million for proteins, up to several bi,Ilion for nucleic acids, and in the millions for polysaccharides such as starch. Individual lipid molecules are much smaller (M, 750 to 1,500) and are not classified as macromolecules. But they can associate noncovalently into very large structures. Cellular membranes are built of enormous noncovalent aggregates of lipid and protein molecules. Given their characteristic information-rich subunit sequences, proteins and nucleic acids are often referred to as informational macromolecules. Some oligosaccharides, as noted above, also serve as informational molecules. Water Proteins Nucleic acids DNA RNA Polysaccharides Lipids Monomeric subunits and intermediates Inorganic ions 70 I o 2 2 1 I 3,000 t i >3,000 10 20 500 20