Часть 1 (1120999), страница 33
Текст из файла (страница 33)
. ()ENZYMEp y r u v a t ec a r b o x y l a s e(.r(1oxa loacetateCARBOXYL GROUP TRANSFER,: 85CATALYSISANDTHEUSEOFENERGYBYCELLSH,OItA-H+HO-BCONDENSATIONA-B-B+HYDROLYSISFigure2-64 Condensationandhydrolysisas opposite reactions.Theof the cellarepolymersmacromoleculesthat areformedfrom subunits(orreactionmonomers)by a condensationTheand arebrokendown by hydrolysis.reactionsareallcondensationunfavorable.energeticallyenergeticallyf a v o r ab l eenergeticallyunfavorablemolecules are made from subunits (or monomers) that are linked together in acondensation reaction, in which the constituents of a water molecule (OH plusH) are removed from the two reactants. Consequently, the reverse reactionthe breakdown of all three tlpes of polymers-occurs by the enzyme-catalyzed.addition of water (hydrolysis).This hydrolysis reaction is energetically favorable, whereas the biosynthetic reactions require an energy input (Figure 2-64) .The nucleic acids (DNA and RNA), proteins, and polysaccharides are allpolymers that are produced by the repeated addition of a monomer onto oneend of a growing chain.
The synthesis reactions for these three types of macromolecules are outlined in Figure 2-65. As indicated, the condensation step ineach case depends on energy from nucleoside triphosphate hydrolysis. And yet,except for the nucleic acids, there are no phosphate groups left in the finalproduct molecules. How are the reactions that releasethe energy of ATP hydrolysis coupled to polymer synthesis?'NTUCLEIC:lAefg5r,POLYSACCHARIDESglucosegrycogenoIoCHzOHe n e r g yo r i g i n a l l yd e r i v e df r o mn u c l e o s i d ter i p h o s p h a t eh y d r o l y s i sooHooHIIO:O:P-OIIoIOHOHproteinamino acidHORttt\oo\l//N-C-C,/l\HROHOHRHHoIP-OIIO: P-OIHYoo- - - - - cl -l lcl-zNz- c - cooHItenergy from nucleosidetriphosphate hydrolysisHO:HzoOHgrycogenPROTEINSIP-O-OHOHRNAOHOHenergyfromnucleosidehydrolysistriphosphateHOttl- _---C -CltlRHHproternROHn-N-CI - C ll-|N- C - Cll'on,zz"proteins,and nucleicFigure2-65 The synthesisof polysaccharides,of eachkind of biologicalpolymerinvolvesthe lossofacids.Synthesisreaction.Not shownis the consumptionofwaterin a condensationthat is requiredto activateeachtriphosphatesnucleosidehigh-energymonomer beforeits addition.In contrast,the reversereaction-thebreakdownof all threetypesof polymers-occursby the simpleadditionof water(hydrolysis).86Chapter2:CellChemistryand BiosynthesisFor each type of macromolecule, an enzyme-catalyzedpathway existswhichresembles that discussed previously for the synthesis of the amino acid glutamine (seeFigure 2-59).
The principle is exactly the same, in that the OH groupthat will be removed in the condensation reaction is first activated by becominginvolved in a high-energy linkage to a second molecule. However, the actualmechanisms used to link ATP hydrolysis to the slmthesis of proteins andpolysaccharidesare more complex than that used for glutamine synthesis,sincea series of high-energy intermediates is required to generate the final highenergy bond that is broken during the condensation step (discussedin Chapter6 for protein synthesis).Each activated carrier has limits in its ability to drive a biosynthetic reaction.The AG for the hydrolysis of ATP to ADP and inorganic phosphate (PJ dependson the concentrations of all of the reactants,but under the usual conditions in acell it is between -11 and -13 kcal/mole (between -46 and -54 kJ/mole). In principle, this hydrolysis reaction could drive an unfavorable reaction with a AG of,perhaps, +10 kcal/mole, provided that a suitable reaction path is available.
Forsome biosynthetic reactions, however, even -13 kcal/mole may not be enough.In these casesthe path of ATP hydrolysis can be altered so that it initially produces AMP and pynophosphate (PPJ,which is itself then hydrolyzed in a subsequent step (Figure 2-66). The whole process makes available a total free-energychange of about -26 kcal/mole. An important type of biosynthetic reaction thatis driven in this way is the synthesis of nucleic acids (polynucleotides) fromnucleoside triphosphates, as illustrated on the right side of Figure 2-62.Note that the repetitive condensation reactions that produce macromolecules can be oriented in one of two ways, giving rise to either the head polymerization or the tail poll'rnerization of monomers.
In so-called head polymerization the reactive bond required for the condensation reaction is carried onthe end of the growing polymer, and it must therefore be regeneratedeach timethat a monomer is added. In this case,each monomer brings with it the reactivebond that will be used in adding the next monomer in the series.ln tail polymerization the reactive bond carried by each monomer is instead used immediately for its or'rmaddition (Figure 2-6S).We shall see in later chapters that both these types of polymerization areused. The synthesisof polynucleotides and some simple polysaccharidesoccursby tail polymerization, for example, whereas the synthesis of proteins occurs bya head polymerization process.(A)(B)ollllo-lP_O_C H 2a d e n o s i n et r i p h o s p h a t e( A T P )Hzo-nro*-.'|Ioo- o - Pi l- lol - P - oP PioopyropnosphateHronl(AMP)a d e n o s i n em o n o p h o s p h a t eIHzoIoo-o-P-oH +Io--o-P-oHIphosphatephosphateoPi+Pi*AMPFigure2-66 An alternativepathway ofATPhydrolysis,in which pyrophosphateis first formed and then hydrolyzed.Thisroutereleasesabouttwiceas muchfreeenergyasthe reactionshownearlierinFigure2-57, and it forms AMP insteadofADP.(A)In the two successivehydrolysisreactions,oxygenatomsfrom theparticipatingwatermoleculesareretainedin the products,as indicated,whereasthe hydrogenatomsdissociateto form free hydrogenions (H+,notshown).(B)Diagramof overallreactioninsummarvform.87ANDTHEUSEOFENERGYCATALYSISBYCELLSh i g h - e n e r g yi n t ediate\P Pr -L.n,o'P -Or\_:_/r f ulseII\i,/p _O_U.\\:'s"75;.ffiI?:ffi:lfl",Figure 2-67 Synthesisof apolynucleotide,RNAor DNA, is amultistep processdriven bY ATPIn the firststep,a nucleosidehydrolysis.is activatedby themonophosphatetransferof the terminalseouentialphosphategroupsfrom two ATPintermediateThe high-energymolecules.triphosphateformed-a nucleosideexistsfreein solutionuntil it reactswiththe growingend of an RNAor a DNAof pyrophosphate.chainwith releaseof the latterto inorganicHydrolysisphosphateis highlyfavorableand helpsto drivethe overallreactionin theForsynthesis.directionof polynucleotidedetails,seeChapter5.OHnucleosidemonophosphateOHSu m m a r yLiuing cellsare highly ordered and need to createorder within themseluesto suruiueand grow.
This is thermodynamically possibteonly becauseof a continual input ofenergy,part of which must be releasedfrom the cellsto their enuironment as heat. Theenergycomesultimatety from the electromagneticradiation of the sun, which driuestheformation of organic moleculesin photosyntheticorganismssuch as greenplants.Animals obtain their energyby eating theseorganic moleculesand oxidizing them ina seriesof enzyme-catalyzedreactions that are coupled to the formation of ATP-acommon currency of energyin all cells.Tbmake possiblethe continual generationof order in cells,the energeticallyfauorable hydrotysisofATP is coupled to energeticallyunfauorable reactions.In the biosynthesisof macromolecules,this is accomplishedby the transfer of phosphategroups toform reactiue phosphorylated intermediates.
Becausethe energetically unfauorablereaction now becomesenergeticallyfauorable,ATP hydrolysisis said to driue the reaction. Polymeric molecules such as proteins, nucleic acids, and polysaccharidesareassembledfrom small actiuated precursor moleculesby repetitiuecondensationreactions thet are driuen in this way. Other reactiuemolecules,called either actiue carriersor coenzymes,transfer other chemical groups in the course of biosynthesis:NADPHtransfershydrogenas a proton plus two electrons(a hydride ion),for example,whereasacetyl CoA transfersan acetylgroup.FATTYACIDS)HEADPOLYMERIZATION (e.9.,PROTEINS,TAILPOLYMERIZATION ( e . g . ,D N A ,R N A ,P O L Y S A C C H A R I D E S )Figure2-68 The orientation of the active intermediatesin the repetitivecondensationreactionsthat formbi-ologicalpolymers.The headgrowth of polymersis comparedwith its alternative,tail growth.As indicated,theseareusedto producedifferenttypesof biologicalmacromolecules.two mechanisms88Chapter2: CellChemistryand BiosynthesisHOWCELLSOBTAINENERGYFROMFOODThe constant supply of energy that cells need to generate and maintain the biological order that keeps them alive comes from the chemical bond energy infood molecules, which thereby serve as fuel for cells.The proteins, lipids, and polysaccharidesthat make up most of the food weeat must be broken down into smaller molecules before our cells can use themeither as a source of energy or as building blocks for other molecules.
EnzFnaticdigestion breaks down the large polymeric molecules in food into theirmonomer subunits-proteins into amino acids, polysaccharides into sugars,and fats into fatty acids and glycerol. After d^igestion, the small orginicmolecules derived from food enter the cltosol of cells, where their gradual oxidation begins.Sugars are particularly important fuel molecules, and they are oxidized insmall controlled steps to carbon dioxide (coz) and water (Figure 2-69). In thissection we trace the major steps in the breakdor.tm,or catabolism, of sugarsandshow how they produce ATB NADH, and other activated carrier molecules inanimal cells.
A very similar pathway also operates in plants, fungi, and manybacteria. As we shall see, the oxidation of fatty acids is equally important forcells. other molecules, such as proteins, can also serve as energy sourceswhenthey are funneled through appropriate enzymatic pathways.Glycolysisls a CentralATP-ProducingPathwayThe major process for oxidizing sugars is the sequence of reactions known asverted into two molecules of pyruuate, each of which contains three carbonatoms.
For each glucose molecule, two molecules of ATp are hydrolyzed to provide energy to drive the early steps, but four molecules of Arp are produced inthe later steps.At the end of glycolysis,there is consequently a nef gain of twomolecules of AIP for each glucose molecule broken down.The glycolltic pathway is outlined in Figure 2-zo and shown in more detailin Panel 2-8 (pp. I?}-IZL). Glycolysis involves a sequence of l0 separate reac_tions, each producing a different sugar intermediate and each caialvzed bv a(A) stepwiseoxidation of sugar in cellsIaqoE( B ) d i r e c tb u r n i n go f s u g a rs m a l la c t i v a t i o ne n e r g i e so v e r c o m ea t b o d yt e m p e r a t u r eo w i n g t o t h epresenceof enzymesS U G A R+ O ,qactivatedc ar n e rmoleculesstoreenergy1wallfreeenergy rsreteaSedas heat;none rsstored&C O ,+ H r OCO, + HrOFigure2-69 Schematicrepresentationof the controlled stepwiseoxidation ofsugarin a cell,comparedwith ordinaryburning,(A)In the cell,enzymescatalyzeoxidationvia a seriesof smallsteosinwhichfreeenergyis transferredinconvenientlysizedpacketsto carriermolecules-mostoftenATPand NADH.At eachstep,an enzymecontrolsthereactionby reducingthe activationenergybarrierthat hasto be surmountedbeforethe specificreactioncan occur.The total free energyreleasedis exactlythe samein (A)and (B).But if the sugarwereinsteadoxidizedto CO2and H2Oina singlestep,as in (B),it would releaseanamountof energymuch largerthancould be capturedfor usefulpurposes.89HOWCELLSOBTAINENERGY.FROMFOODone moleculeof glucoseenergyinvestmentto berecoupeolaterfructose 1,6bisphosphateICHOCHOHCHOHItwo moleculesofglyceraldehyde3-phosphateicH2o PI@Ia|III<COOtwo moleculesof pyruvatesrresICHOC:oICHrsrEPT,',r,esrEPc l e a v a g eo fs i x - c rab o nsugarto twoth ree-carbons u g ar sIIt---*IIIItIenergygenerationsTEP1Ol-cooIICH:different enzyrne.
![](https://s.studizba.com/z.php?f=/templates/si/i/noavatar.png&w=100&h=100&t=1"){kind=avatar}
