生物代謝授課第1頁(yè)/共308頁(yè)CHAPTER7

METABOLISM

代謝總論P(yáng)artⅠPrinciplesofbioenergeticsPartⅡ

Glycolysis,gluconeogenesis,andthepentosephosphatepathwayPartⅢ

Principlesofmetabolicregulation:glucoseandglycogenPartⅣThecitricacidcyclePartⅤFattyacidcatabolismPartⅥLipidbiosynthesis第2頁(yè)/共308頁(yè)新陳代謝完成的4大功能：Metabolismisahighlycoordinatedcellularactivityinwhichmanymultienzymesystems(metabolicpathways)cooperateto:(1)obtainchemicalenergybycapturingsolarenergyordegradingenergy-richnutrientsfromtheenvironment;捕獲太陽(yáng)能或降解環(huán)境中的含高能的營(yíng)養(yǎng)物來(lái)獲得化學(xué)能

(2)convertnutrientmoleculesintothecell’sowncharacteristicmolecules,includingprecursorsofmacromolecules;使?fàn)I養(yǎng)分子轉(zhuǎn)化為細(xì)胞自己的特征分子

(3)polymerizemonomericprecursorsintomacromolecules:proteins,nucleicacids,andpolysaccharides;使單體分子聚合成大分子

(4)synthesizeanddegradebiomoleculesrequiredforspecializedcellularfunctions,suchasmembranelipids,intracellularmessengers,andpigments.合成和降解細(xì)胞特殊功能所需的生物大分子第3頁(yè)/共308頁(yè)Autotrophs自養(yǎng)生物

(suchasphotosyntheticbacteriaandvascularplants)canusecarbondioxidefromtheatmosphereastheirsolesourceofcarbon,fromwhichtheyconstructalltheircarboncontainingbiomolecules以大氣中的CO2作為惟一碳源，產(chǎn)生所有含碳生物分子Heterotrophs異養(yǎng)生物cannotuseatmosphericcarbondioxideandmustobtaincarbonfromtheirenvironmentintheformofrelativelycomplexorganicmoleculessuchasglucose.必須從環(huán)境中獲取以相對(duì)復(fù)雜形式存在的含碳化合物作為碳源如葡萄糖。生物物種根據(jù)它們從環(huán)境中攝取碳的化學(xué)形式分為兩大類：第4頁(yè)/共308頁(yè)FIGURE1Cyclingofcarbondioxideandoxygenbetweentheautotrophic(photosynthetic)andheterotrophicdomainsinthebiosphere.生物圈中自養(yǎng)界（光合作用）和異養(yǎng)界之間的CO2和O2的循環(huán)Theflowofmassthroughthiscycleisenormous;about4×1011metrictonsofcarbonareturnedoverinthebiosphereannually.循環(huán)中的物質(zhì)流動(dòng)非常大；生物圈中每年大約4×1011噸碳被轉(zhuǎn)化。第5頁(yè)/共308頁(yè)Alllivingorganismsalsorequireasourceofnitrogen,whichisnecessaryforthesynthesisofaminoacids,nucleotides,andothercompounds.所有的生物還需要氮源，是合成氨基酸、核苷酸等化合物所必需的。Plantscangenerallyuseeitherammoniaornitrateastheirsolesourceofnitrogen植物一般使用氨或硝酸鹽作為惟一的氮源Vertebratesmustobtainnitrogenintheformofaminoacidsorotherorganiccompounds.脊椎動(dòng)物必須以氨基酸或其他有機(jī)化合物的形式獲取氮。第6頁(yè)/共308頁(yè)FIGURE2Cyclingofnitrogeninthebiosphere.生物圈中的氮循環(huán)Gaseousnitrogen(N2)makesup80%oftheearth’satmosphere.氮?dú)庹嫉厍虼髿鈱拥?0%固氮細(xì)菌反硝化細(xì)菌硝化細(xì)菌第7頁(yè)/共308頁(yè)Metabolism，metabolicpathways，metabolitesandintermediarymetabolism

代謝、代謝途徑、代謝物和中間代謝

代謝Metabolism,thesumofallthechemicaltransformationstakingplaceinacellororganism,occursthroughaseriesofenzyme-catalyzedreactionsthatconstitutemetabolicpathways.代謝是一個(gè)細(xì)胞或有機(jī)體中發(fā)生的所有反應(yīng)的總和。一系列酶催化反應(yīng)組成代謝途徑。Theprecursorisconvertedintoaproductthroughaseriesofmetabolicintermediatescalledmetabolites.前體通過(guò)一系列代謝中間物，或稱為代謝物，被轉(zhuǎn)化為產(chǎn)物。Thetermintermediarymetabolismisoftenappliedtothecombinedactivitiesofallthemetabolicpathwaysthatinterconvertprecursors,metabolites,andproductsoflowmolecularweight(generally,Mr1,000).中間代謝用以描述所有用于轉(zhuǎn)化低相對(duì)分子質(zhì)量的前體、代謝物和產(chǎn)物的代謝路徑的組合。第8頁(yè)/共308頁(yè)Catabolism分解代謝Catabolismisthedegradativephaseofmetabolisminwhichorganicnutrientmolecules(carbohydrates,fats,andproteins)areconvertedintosmaller,simplerendproducts(suchaslacticacid,CO2,NH3).分解代謝是代謝中的降解階段。Catabolicpathwaysreleaseenergy,someofwhichisconservedintheformationofATPandreducedelectroncarriers(NADH,NADPH,andFADH2);therestislostasheat.分解代謝途徑釋放能量第9頁(yè)/共308頁(yè)Anabolism合成代謝Inanabolism,alsocalledbiosynthesis,small,simpleprecursorsarebuiltupintolargerandmorecomplexmolecules,includinglipids,polysaccharides,proteins,andnucleicacids.在合成代謝中，小而簡(jiǎn)單的前體被構(gòu)造成大而復(fù)雜的分子Anabolicreactionsrequireaninputofenergy,generallyintheformofthephosphorylgroup磷?；鵷ransferpotentialofATPandthereducingpowerofNADH,NADPH,andFADH2.合成代謝反應(yīng)需要能量第10頁(yè)/共308頁(yè)FIGURE3Energyrelationshipsbetweencatabolicandanabolicpathways.分解代謝和合成代謝之間的能量關(guān)系CatabolicpathwaysdeliverchemicalenergyintheformofATP,NADH,NADPH,andFADH2.Theseenergycarriersareusedinanabolicpathwaystoconvertsmallprecursormoleculesintocellmacromolecules.第11頁(yè)/共308頁(yè)Threetypesofnonlinearmetabolicpathways

3種類型的非線性代謝路徑(a)Converging,catabolic聚集型:分解代謝(b)Diverging,anabolic發(fā)散型:合成代謝(c)Cyclic循環(huán)型:

循環(huán)中的某一起始物如草酰乙酸被重復(fù)產(chǎn)生并重新進(jìn)入循環(huán)途徑。Acetate乙酸酯,akeymetabolicintermediate,isthebreakdownproductofavarietyoffuels(a),servesastheprecursorforanarrayofproducts(b),andisconsumedinthecatabolicpathwayknownasthecitricacidcycle檸檬酸循環(huán)(c).第12頁(yè)/共308頁(yè)FIGURE4Threetypesofnonlinearmetabolicpathways.第13頁(yè)/共308頁(yè)Regulationbetweenanabolicandcatabolicreaction合成代謝和分解代謝反應(yīng)的調(diào)節(jié)Mostcellshavetheenzymestocarryoutboththedegradationandthesynthesisoftheimportantcategoriesofbiomolecules.大多數(shù)細(xì)胞都有降解和合成重要類型生物分子的酶Theanabolicandcatabolicreactionsequences:whenonesequenceisactive,theotherissuppressed.合成代謝和分解代謝的反應(yīng)順序是被相互正反調(diào)節(jié)的。第14頁(yè)/共308頁(yè)Catabolicandanabolicpathwaysthatconnectthesametwoendpoints(glucose→→pyruvateandpyruvate→→glucose,forexample)mayemploymanyofthesameenzymes,butinvariablyatleastoneofthestepsiscatalyzedbydifferentenzymesinthecatabolicandanabolicdirections,andtheseenzymesarethesitesofseparateregulation.連接兩個(gè)端點(diǎn)的分解代謝和合成代謝途徑可以使用很多相同的酶，但是總有至少一步反應(yīng)在分解代謝和合成代謝中試分別由不同的酶完成的，而且這些酶是分開調(diào)節(jié)的位點(diǎn)。第15頁(yè)/共308頁(yè)Asafurthercontributiontotheseparateregulationofcatabolicandanabolicreactionsequences,pairedcatabolicandanabolicpathwayscommonlytakeplaceindifferentcellularcompartments:forexample,fattyacidcatabolisminmitochondria,fattyacidsynthesisinthecytosol.成對(duì)的兩條途徑經(jīng)常發(fā)生在細(xì)胞的不同區(qū)域中：如脂肪酸的降解在線粒體中，而脂肪酸的合成在胞漿中。第16頁(yè)/共308頁(yè)Fivemainreactionclasses

5個(gè)主要的反應(yīng)類型Mostofthereactionsinlivingcellsfallintooneoffivegeneralcategories:(1)oxidation-reductions氧化-還原(2)reactionsthatmakeorbreakcarbon–carbonbondsc-c鍵形成和斷裂(3)internalrearrangements,isomerizations,andeliminations內(nèi)部重排、異構(gòu)化和消除(4)grouptransfers基團(tuán)轉(zhuǎn)移(5)freeradicalreactions.自由基反應(yīng)

第17頁(yè)/共308頁(yè)TwobasicchemicalprinciplesFirst,acovalentbondconsistsofasharedpairofelectrons,andthebondcanbebrokenintwogeneralways:homolyticcleavage均裂斷鍵,heterolyticcleavage異裂斷鍵.一個(gè)共價(jià)鍵由共享的成對(duì)電子組成；可以以兩種方式斷裂：均裂斷鍵和異裂斷鍵。Thesecondisthatmanybiochemicalreactionsinvolveinteractionsbetweennucleophiles親核(functionalgroupsrichinelectronsandcapableofdonatingthem)andelectrophiles親電(electrondeficientfunctionalgroupsthatseekelectrons).許多生化反應(yīng)包括了親核和親電相互作用。第18頁(yè)/共308頁(yè)FIGURE5TwomechanismsforcleavageofaC-CorC-Hbond.C-CC-H鍵斷裂的兩種機(jī)理第19頁(yè)/共308頁(yè)Inhomolyticcleavages均裂斷鍵,eachatomkeepsoneofthebondingelectrons,resultingintheformationofcarbonradicals(carbonshavingunpairedelectrons)orunchargedhydrogenatoms.Inheterolyticcleavages異裂斷鍵,oneoftheatomsretainsbothbondingelectrons.Thiscanresultintheformationofcarbanions碳陰離子,carbocations碳陽(yáng)離子,protons質(zhì)子,orhydrideions氫負(fù)離子.第20頁(yè)/共308頁(yè)1.Oxidation-reductionreactions氧化還原反應(yīng)Carbonatomsencounteredinbiochemistrycanexistinfiveoxidationstates,dependingontheelementswithwhichcarbonshareselectrons.Dehydrogenase脫氫酶Oxidases氧化酶Oxygenases加氧酶第21頁(yè)/共308頁(yè)FIGURE6Theoxidationstatesofcarboninbiomolecules.生物分子中C的氧化態(tài)Eachcompoundisformedbyoxidationoftheredcarboninthecompoundlistedaboveit.Carbondioxideisthemosthighlyoxidizedformofcarbonfoundinlivingsystems.第22頁(yè)/共308頁(yè)FIGURE7Anoxidation-reductionreaction.Shownhereistheoxidationoflactate乳酸

topyruvate丙酮酸.Inthisdehydrogenation,twoelectronsandtwohydrogenions(theequivalentoftwohydrogenatoms)areremovedfromC-2oflactate,analcohol,toformpyruvate,aketone.Incellsthereactioniscatalyzedbylactatedehydrogenaseandtheelectronsaretransferredtoacofactorcallednicotinamideadeninedinucleotide煙酰胺腺嘌呤二核苷酸.Thisreactionisfullyreversible;pyruvatecanbereducedbyelectronsfromthecofactor.第23頁(yè)/共308頁(yè)2.Reactionsthatmakeorbreakcarbon–carbonbondsc-c鍵形成和斷裂HeterolyticcleavageofaC-Cbondyieldsacarbanion碳陰離子andacarbocation碳陽(yáng)離子(Fig.5).Conversely,theformationofaC-Cbondinvolvesthecombinationofanucleophiliccarbanion親核負(fù)碳離子andanelectrophiliccarbocation親電碳陽(yáng)離子.Groupswithelectronegativeatomsplaykeyrolesinthesereactions.在這些反應(yīng)中，擁有電負(fù)性原子的基團(tuán)發(fā)揮關(guān)鍵作用。Carbonylgroups羰基

areparticularlyimportantinthechemicaltransformationsofmetabolicpathways.第24頁(yè)/共308頁(yè)FIGURE8Carbon–carbonbondformationreactions.(C)醇醛縮合,Claisen酯縮合,脫羧第25頁(yè)/共308頁(yè)3.Internalrearrangements,isomerizations,andeliminations

內(nèi)部重排、異構(gòu)化和消除Anothercommontypeofcellularreactionisanintramolecularrearrangement,inwhichredistribution重新分配ofelectronsresultsinisomerization異構(gòu)化,transpositionofdoublebonds,orcis-transrearrangementsofdoublebonds.EliminationofwaterintroducesaC=Cbondbetweentwocarbonsthatpreviouslyweresaturated.Similarreactionscanresultintheeliminationofalcoholsandamines.第26頁(yè)/共308頁(yè)FIGURE9Isomerizationandeliminationreactions.(b)Enediolintermediate

烯醇式相互轉(zhuǎn)化第27頁(yè)/共308頁(yè)FIGURE9Isomerizationandeliminationreactions.(a)Theconversionofglucose6-phosphatetofructose6-phosphate,areactionofsugarmetabolismcatalyzedbyphosphohexoseisomerase.(b)Thisreactionproceedsthroughanenediolintermediate.Thecurvedbluearrowsrepresentthemovementofbondingelectronsfromnucleophile(pink)toelectrophile(blue).B1andB2arebasicgroupsontheenzyme;theyarecapableofdonatingandacceptinghydrogenions(protons)asthereactionprogresses.第28頁(yè)/共308頁(yè)4.Grouptransferreactions基團(tuán)轉(zhuǎn)移Thetransferofacyl?；?glycosyl糖基,andphosphoryl磷酰基groupsfromonenucleophile親核試劑

toanotheriscommoninlivingcells.Acylgrouptransfergenerallyinvolvestheadditionofanucleophiletothecarbonylcarbonofanacylgrouptoformatetrahedralintermediate四面體中間物.第29頁(yè)/共308頁(yè)FIGURE10Alternativewaysofshowingthestructureofinorganicorthophosphate正磷酸鹽.第30頁(yè)/共308頁(yè)FIGURE10Alternativewaysofshowingthestructureofinorganicorthophosphate正磷酸鹽.(a)Inone(inadequate)representation,threeoxygensaresingle-bondedtophosphorus,andthefourthisdouble-bonded,allowingthefourdifferentresonancestructuresshown.(b)Thefourresonancestructurescanberepresentedmoreaccuratelybyshowingallfourphosphorus–oxygenbondswithsomedouble-bondcharacter;thehybridorbitalssorepresentedarearrangedinatetrahedron正四面體withPatitscenter.(c)WhenanucleophileZ(inthiscase,the-OHonC-6ofglucose)attacksATP,itdisplacesADP(W).InthisSN2reaction,apentacovalentintermediate五角共價(jià)中間物

(d)formstransiently.第31頁(yè)/共308頁(yè)5.FreeradicalreactionsOncethoughttoberare,thehomolyticcleavageofcovalentbondstogeneratefreeradicalshasnowbeenfoundinarangeofbiochemicalprocesses.Someexamplesarethereactionsofmethylmalonyl-CoAmutase甲基丙二酰輔酶A變位酶,ribonucleotidereductase核苷酸還原酶,andDNAphotolyase光修復(fù)酶.第32頁(yè)/共308頁(yè)P(yáng)artI

PrinciplesofBioenergetics

生物能量學(xué)原理

1.1BioenergeticsandThermodynamics

生物能量學(xué)和熱力學(xué)1.2PhosphorylGroupTransfersandATP

磷?；鶊F(tuán)轉(zhuǎn)移和ATP1.3BiologicalOxidation-ReductionReactions生物氧化-還原反應(yīng)第33頁(yè)/共308頁(yè)生物能量學(xué)是定量研究發(fā)生在活細(xì)胞中的能量轉(zhuǎn)換及這些轉(zhuǎn)換背后化學(xué)過(guò)程的特性和功能的科學(xué)吸收能量和并將其轉(zhuǎn)變成生物功是所有活的有機(jī)體的基本特征。有機(jī)體具有多種能量轉(zhuǎn)換形式。使用燃料中的化學(xué)能將簡(jiǎn)單的前體合成為高度有序的大分子。將燃料中的化學(xué)能轉(zhuǎn)化為濃度梯度和電梯度、運(yùn)動(dòng)和熱，甚至少數(shù)生物如螢火蟲和深海魚能將其轉(zhuǎn)化為光。能進(jìn)行光合作用的生物可將光能轉(zhuǎn)變邊為能量的各種形式。第34頁(yè)/共308頁(yè)1.1BioenergeticsandThermodynamics能量學(xué)和熱力學(xué)1.1.1BiologicalEnergyTransformationsObeytheLawsofThermodynamics生物能量轉(zhuǎn)換遵守?zé)崃W(xué)定律1.1.2CellsRequireSourcesofFreeEnergy細(xì)胞獲得自由能的途徑1.1.3TheStandardFree-EnergyChangeIsDirectlyRelatedtotheEquilibriumConstant標(biāo)準(zhǔn)自由能變化直接和平衡常數(shù)相關(guān)1.1.4ActualFree-EnergyChangesDependonReactantandProductConcentrations實(shí)際自由能變化依賴于反應(yīng)物和產(chǎn)物的濃度1.1.5StandardFree-EnergyChangesAreAdditive標(biāo)準(zhǔn)自由能變化是可以加和的第35頁(yè)/共308頁(yè)1.1.1BiologicalEnergyTransformationsObeytheLawsofThermodynamics生物能量轉(zhuǎn)換遵守?zé)崃W(xué)定律熱力學(xué)2個(gè)基本定律：第一定律：能量守恒定律對(duì)于任何物理及化學(xué)變化，宇宙中能量總量保持不變，能量也許會(huì)變化形式或從一個(gè)區(qū)域運(yùn)輸?shù)搅硪粋€(gè)區(qū)域，但它不可能被創(chuàng)造或者被消滅。熱力學(xué)第二定律：宇宙中總是趨向于增加無(wú)序性，也即在所有自然過(guò)程中，體系中的熵增加。Thesecondlawofthermodynamics,whichcanbestatedinseveralforms,saysthattheuniversealwaystendstowardincreasingdisorder:inallnaturalprocesses,theentropyoftheuniverseincreases.第36頁(yè)/共308頁(yè)在化學(xué)反應(yīng)中描述能量變化的熱力學(xué)3個(gè)變量Gibbsfreeenergy,G,吉布斯自由能表示在恒溫恒壓下反應(yīng)中可做功的能量.

Whenareactionproceedswiththereleaseoffreeenergy(thatis,whenthesystemchangessoastopossesslessfreeenergy),thefree-energychange,△G,hasanegativevalueandthereactionissaidtobeexergonic釋放能量.放能反應(yīng)，自由能變化△G為負(fù)值Inendergonicreactions,thesystemgainsfreeenergyand△Gispositive.在吸收能量的反應(yīng)中，系統(tǒng)獲得了自由能，△G值是正的。第37頁(yè)/共308頁(yè)Enthalpy,H,焓istheheatcontent熱容量ofthereactingsystem.焓是反應(yīng)系統(tǒng)的熱容。Itreflectsthenumberandkindsofchemicalbondsinthereactantsandproducts.反映了反應(yīng)物和產(chǎn)物中化學(xué)鍵的種類和數(shù)量。

Whenachemicalreactionreleasesheat,itissaidtobeexothermic放熱的;theheatcontentoftheproductsislessthanthatofthereactantsand△Hhas,byconvention,anegativevalue.當(dāng)化學(xué)反應(yīng)釋放能量時(shí)，產(chǎn)物的熱容量比反應(yīng)物的熱容量少，△H是負(fù)值Reactingsystemsthattakeupheatfromtheirsurroundingsareendothermic吸熱的andhavepositivevaluesof△H.從環(huán)境中吸收熱量的反應(yīng)系統(tǒng)是吸能的，△H是正值。第38頁(yè)/共308頁(yè)Entropy,S,熵isaquantitativeexpressionfortherandomnessordisorderinasystem.定量描述系統(tǒng)無(wú)序程度的物理量。Whentheproductsofareactionarelesscomplexandmoredisorderedthanthereactants,thereactionissaidtoproceedwithagaininentropy.當(dāng)一個(gè)反應(yīng)的產(chǎn)物比反應(yīng)物簡(jiǎn)單和更加無(wú)序時(shí)，反應(yīng)過(guò)程中熵增加。第39頁(yè)/共308頁(yè)TABLE1–1SomePhysicalConstantsandUnitsUsedinThermodynamics某些在熱力學(xué)中用到的物理常數(shù)和單位第40頁(yè)/共308頁(yè)在適合生物系統(tǒng)存在的條件下，自由能、熵和焓的變化滿足以下公式：Undertheconditionsexistinginbiologicalsystems(includingconstanttemperatureandpressure),changesinfreeenergy,enthalpy,andentropyarerelatedtoeachotherquantitativelybytheequation△Shasapositivesignwhenentropyincreases△Hhasanegativesignwhenheatisreleasedbythesystemtoitssurroundings.△Gofaspontaneouslyreactingsystemisalwaysnegative.自發(fā)反應(yīng)系統(tǒng)的△G總是負(fù)的。第41頁(yè)/共308頁(yè)1.1.2CellsRequireSourcesofFreeEnergy

細(xì)胞獲得自由能的途徑Heterotrophiccellsacquirefreeenergyfromnutrientmolecules異養(yǎng)細(xì)胞從營(yíng)養(yǎng)分子中獲得自由能photosyntheticcellsacquireitfromabsorbedsolarradiation光合細(xì)胞從吸收的太陽(yáng)光中獲得自由能.BothkindsofcellstransformthisfreeenergyintoATPandotherenergy-richcompoundscapableofprovidingenergyforbiologicalworkatconstanttemperature.這幾種細(xì)胞將自由能存入ATP和其他能在常溫下為生物活動(dòng)提供能量的富能化合物中。第42頁(yè)/共308頁(yè)1.1.3TheStandardFree-EnergyChangeIsDirectlyRelatedtotheEquilibriumConstant

標(biāo)準(zhǔn)自由能變化直接和平衡常數(shù)相關(guān)Thestandardfree-energychangeofachemicalreactionissimplyanalternativemathematicalwayofexpressingitsequilibriumconstant.化學(xué)反應(yīng)中標(biāo)準(zhǔn)自由能的變化僅僅是表示其平衡常數(shù)的另一種數(shù)學(xué)方式。第43頁(yè)/共308頁(yè)TABLE1–2RelationshipbetweentheEquilibriumConstantsandStandardFree-EnergyChangesofChemicalReactions第44頁(yè)/共308頁(yè)TABLE1–3RelationshipsamongKeq,△G’°andtheDirectionofChemicalReactionsunderStandardConditions第45頁(yè)/共308頁(yè)1.1.4ActualFree-EnergyChangesDependonReactantandProductConcentrations

實(shí)際自由能變化依賴于反應(yīng)物和產(chǎn)物的濃度About:△G’°

標(biāo)準(zhǔn)自由能變化每一個(gè)化學(xué)反應(yīng)都有一個(gè)特征性的標(biāo)準(zhǔn)自由能變化，其值可能是正、負(fù)或零，這依賴于反應(yīng)的平衡常數(shù)。Eachchemicalreactionhasacharacteristicstandardfree-energychange,whichmaybepositive,negative,orzero,dependingontheequilibriumconstantofthereaction.Thestandardfreeenergychangetellsusinwhichdirectionandhowfaragivenreactionmustgotoreachequilibriumwhentheinitialconcentrationofeachcomponentis1.0M,thepHis7.0,thetemperatureis25℃,andthepressureis101.3kPa.Thus△G’°isaconstant:ithasacharacteristic,unchangingvalueforagivenreaction.△G’°

標(biāo)準(zhǔn)自由能變化：是一個(gè)常數(shù)。對(duì)每一個(gè)反應(yīng)都有一個(gè)特定的不變的值。第46頁(yè)/共308頁(yè)About:△G實(shí)際自由能變化theactualfree-energychange,△G,isafunctionofreactantandproductconcentrationsandofthetemperatureprevailingduringthereaction,whichwillnotnecessarilymatchthestandardconditionsasdefinedabove.一個(gè)關(guān)于反應(yīng)物和產(chǎn)物濃度以及反應(yīng)進(jìn)行時(shí)溫度的函數(shù)。Moreover,the△Gofanyreactionproceedingspontaneouslytowarditsequilibriumisalwaysnegative,becomeslessnegativeasthereactionproceeds,andiszeroatthepointofequilibrium,indicatingthatnomoreworkcanbedonebythereaction.任何能自發(fā)向平衡態(tài)進(jìn)行的反應(yīng)其△G總是負(fù)的，并隨著反應(yīng)進(jìn)行負(fù)值減少，在平衡態(tài)達(dá)到零，這表明反應(yīng)無(wú)法再做更多的功了。第47頁(yè)/共308頁(yè)△G’°and△GforanyreactionA+B≒C+Darerelatedbytheequation：whenareactionisatequilibrium—whenthereisnoforcedrivingthereactionineitherdirectionand△Giszero—Equation13–3reducesto：第48頁(yè)/共308頁(yè)反應(yīng)自由能的變化與反應(yīng)的途徑無(wú)關(guān)Thefree-energychangeforareactionisindependentofthepathwaybywhichthereactionoccurs;反應(yīng)自由能的變化與反應(yīng)的途徑無(wú)關(guān)。

itdependsonlyonthenatureandconcentrationoftheinitialreactantsandthefinalproducts.Enzymescannot,therefore,changeequilibriumconstants;buttheycananddoincreasetherateatwhichareactionproceedsinthedirectiondictatedbythermodynamics.酶不能改變平衡常數(shù)，卻能在熱力學(xué)指定的反應(yīng)方向下改變反應(yīng)速度。第49頁(yè)/共308頁(yè)1.1.5StandardFree-EnergyChangesAreAdditive

標(biāo)準(zhǔn)自由能變化是可以加和的The△G’°valuesofsequentialchemicalreactionsareadditive.第50頁(yè)/共308頁(yè)Forexample,thesynthesisofglucose6-phosphateisthefirststepintheutilizationofglucosebymanyorganisms:第51頁(yè)/共308頁(yè)△G’°isawayofexpressingtheequilibriumconstantforareaction----Equilibriumconstants

aremultiplicative

平衡常數(shù)是相乘關(guān)系第52頁(yè)/共308頁(yè)1.2PhosphorylGroupTransfersandATP

磷?；鶊F(tuán)轉(zhuǎn)移和ATPHeterotrophiccellsobtainfreeenergyinachemicalformbythecatabolismofnutrientmolecules,andtheyusethatenergytomakeATPfromADPandPi.異養(yǎng)細(xì)胞通過(guò)營(yíng)養(yǎng)分子的分解代謝以化學(xué)形式獲得自由能，它們使ADP和Pi合成ATP。ATPthendonatessomeofitschemicalenergytoendergonicprocesses.ThisdonationofenergyfromATPgenerallyinvolvesthecovalentparticipationofATPinthereactionthatistobedriven,withtheeventualresultthatATPisconvertedtoADPandPior,insomereactions,toAMPand2Pi.ATP的能量供給一般涉及到ATP共價(jià)參與所驅(qū)動(dòng)的反應(yīng)，最終結(jié)果是ATP被轉(zhuǎn)變成ADP和Pi，或AMP和2Pi.第53頁(yè)/共308頁(yè)作為聯(lián)系合成代謝和分解代謝的能量貨幣ATP的特殊作用ATP是連接釋放能量和吸收能量的細(xì)胞過(guò)程的共享化學(xué)中間體。第54頁(yè)/共308頁(yè)1.2.1TheFree-EnergyChangeforATPHydrolysisIsLargeandNegative

ATP水解的自由能變化很大且是負(fù)值Figure1–1summarizesthechemicalbasisfortherelativelylarge,negative,standardfreeenergyofhydrolysisofATP.概括了ATP水解的標(biāo)準(zhǔn)自由能變化的化學(xué)基礎(chǔ)AlthoughthehydrolysisofATPishighlyexergonic(△G’°=-30.5kJ/mol),themoleculeiskineticallystableatpH7becausetheactivationenergyforATPhydrolysisisrelativelyhigh.盡管ATP水解是高度放能的，在pH7時(shí)其分子在動(dòng)力學(xué)上是穩(wěn)定的，這是因?yàn)锳TP水解的活化能相當(dāng)高。Rapidcleavageofthephosphoanhydridebonds磷酸酐鍵occursonlywhencatalyzedbyanenzyme.磷酸酐鍵的快速斷裂只有在酶的催化下才能發(fā)生。第55頁(yè)/共308頁(yè)FIGURE1–1Chemicalbasisforthelargefree-energychangeassociatedwithATPhydrolysis水解，電荷排斥減弱通過(guò)引起電荷分離，水解釋放了在ATP的四個(gè)負(fù)電荷間的靜電斥力水解時(shí)釋放的Pi被共振雜化分子的形成所穩(wěn)定水解產(chǎn)生的ADP2-立刻離子化，釋放出一個(gè)質(zhì)子到含有非常低H+的介質(zhì)中產(chǎn)物Pi和ADP具有比ATP更大的溶劑化程度（水合），穩(wěn)定了產(chǎn)物。共振穩(wěn)定作用電離第56頁(yè)/共308頁(yè)FIGURE1–2Mg2+

andATP.FormationofMg2+complexespartiallyshieldsthenegativechargesandinfluencestheconformationofthephosphategroupsinnucleotidessuchasATPandADP.Mg2+復(fù)合物的形成部分屏蔽了負(fù)電荷，并影響了核苷酸（如ATP和ADP）中磷酸基團(tuán)的構(gòu)象大多數(shù)涉及ATP作為磷酸基團(tuán)提供者的酶促反應(yīng)，真正的底物是MgATP2-第57頁(yè)/共308頁(yè)1.2.2OtherPhosphorylatedCompoundsandThioestersAlsoHaveLargeFreeEnergiesofHydrolysis

其他磷酸化合物和硫脂也有很大的水解自由能FIGURE1–3Hydrolysisofphosphoenolpyruvate(PEP).Catalyzedbypyruvatekinase,thisreactionisfollowedbyspontaneoustautomerization互變異構(gòu)

oftheproduct,pyruvate.TautomerizationisnotpossibleinPEP,andthustheproductsofhydrolysisarestabilizedrelativetothereactants.水解的產(chǎn)物比反應(yīng)物更穩(wěn)定。磷酸烯醇式丙酮酸第58頁(yè)/共308頁(yè)FIGURE1–4Hydrolysisof1,3-bisphosphoglycerate.甘油酸-1，3-二磷酸的水解Thedirectproductofhydrolysisis3-phosphoglycericacid,withanundissociatedcarboxylicacidgroup未解離的羧酸基團(tuán),butdissociationoccursimmediately.Thisionizationandtheresonancestructuresitmakespossiblestabilizetheproductrelativetothereactants.離子化合共振穩(wěn)定了產(chǎn)物ResonancestabilizationofPifurthercontributestothenegativefreeenergychange.Pi的共振穩(wěn)定進(jìn)一步對(duì)負(fù)的自由能變化作出貢獻(xiàn)。第59頁(yè)/共308頁(yè)FIGURE1–5Hydrolysisofphosphocreatine磷酸肌酸

.BreakageoftheP-Nbondinphosphocreatineproducescreatine肌酸,whichisstabilizedbyformationofaresonancehybrid.磷酸肌酸中P-N鍵的斷裂產(chǎn)生肌酸，被共振雜化分子的形成所穩(wěn)定。Theotherproduct,Pi,isalsoresonancestabilized.其他產(chǎn)物也是共振穩(wěn)定的。第60頁(yè)/共308頁(yè)硫脂也有很大負(fù)值的水解標(biāo)準(zhǔn)自由能。乙酰輔酶A是代謝中起重要作用的硫脂化合物。乙?；鶊F(tuán)被酰基轉(zhuǎn)移、縮合或氧化還原反應(yīng)激活在反應(yīng)物和被共振穩(wěn)定的水解物間的自由能差異，硫脂比氧脂大。第61頁(yè)/共308頁(yè)FIGURE1–6Hydrolysisofacetyl-coenzymeA.

Acetyl-CoAisathioesterwithalarge,negative,standardfreeenergyofhydrolysis.乙酰輔酶A是一種有很大水解自由能的硫脂。Thioesterscontainasulfuratominthepositionoccupiedbyanoxygenatominoxygenesters.第62頁(yè)/共308頁(yè)Acetyl-coenzymeA,oracetyl-CoA,isoneofmanythioestersimportantinmetabolism.Theacylgroupinthesecompoundsisactivatedfortransacylation?；D(zhuǎn)移,condensation縮合,oroxidation-reductionreactions.第63頁(yè)/共308頁(yè)TABLE1–6StandardFreeEnergiesofHydrolysisofSomePhosphorylatedCompoundsandAcetyl-CoA(aThioester)第64頁(yè)/共308頁(yè)小結(jié)：對(duì)于有很大的負(fù)標(biāo)準(zhǔn)自由能變化的水解反應(yīng)，產(chǎn)物比反應(yīng)物更加穩(wěn)定。原因如下：(1)thebondstraininreactantsduetoelectrostaticrepulsionisrelievedbychargeseparation,asforATP;反應(yīng)物中由于靜電排斥產(chǎn)生的鍵張力因電荷分離而釋放。(2)theproductsarestabilizedbyionization,asforATP,acylphosphates,andthioesters;產(chǎn)物被離子化所穩(wěn)定(3)theproductsarestabilizedbyisomerization(tautomerization),asforphosphoenolpyruvate;產(chǎn)物被異構(gòu)化所穩(wěn)定(4)theproductsarestabilizedbyresonance,asforcreatinereleasedfromphosphocreatine,carboxylateionreleasedfromacylphosphatesandthioesters,andphosphate(Pi)releasedfromanhydrideoresterlinkages.產(chǎn)物被共振作用所穩(wěn)定第65頁(yè)/共308頁(yè)1.2.3ATPProvidesEnergybyGroupTransfers,NotbySimpleHydrolysis

ATP通過(guò)基團(tuán)轉(zhuǎn)移提供能量，而不是僅僅通過(guò)水解提供能量OneistemptedtosaythatanATP-dependentreactionis“drivenbythehydrolysisofATP.”Thisisnotthecase.錯(cuò)誤的說(shuō)法：ATP依賴的反應(yīng)是“ATP水解驅(qū)動(dòng)的”實(shí)際上，大多情況下ATP按兩步水解：ATP分子的磷?；蚪沽柞；蛳佘账岵糠质紫缺晦D(zhuǎn)移到一個(gè)底物分子或轉(zhuǎn)移到一個(gè)酶的單個(gè)氨基酸殘基上，共價(jià)連接到底物或酶上兵提高了自由能含量；第二步，被轉(zhuǎn)移的含磷酸部分被取代，產(chǎn)生了Pi、PPi或AMP。第66頁(yè)/共308頁(yè)FIGURE1–8ATPhydrolysisintwosteps.

(a)ThecontributionofATPtoareactionisoftenshownasasinglestep,butisalmostalwaysatwo-stepprocess.(b)ShownhereisthereactioncatalyzedbyATPdependentglutaminesynthetase.①AphosphorylgroupistransferredfromATPtoglutamate,then②thephosphorylgroupisdisplacedbyNH3andreleasedasPi.磷?；鶊F(tuán)被NH3取代，釋放出Pi.第67頁(yè)/共308頁(yè)ATP或GTP的直接水解SomeprocessesdoinvolvedirecthydrolysisofATP(orGTP),however.Forexample,noncovalentbindingofATP(orofGTP),followedbyitshydrolysistoADP(orGDP)andPi,canprovidetheenergytocyclesomeproteinsbetweentwoconformations,producingmechanicaltriggeredbyhormonesorbyotherextracellularfactors.一些過(guò)程確實(shí)涉及到了ATP或GTP的直接水解。例如，ATP的非共價(jià)結(jié)合，通過(guò)ATP水解成ADP和Pi提供能量，使某些蛋白質(zhì)在兩種構(gòu)象中循環(huán)，產(chǎn)生機(jī)械運(yùn)動(dòng)。這發(fā)生在肌肉收縮、酶沿著DNA運(yùn)動(dòng)和核糖體沿著信使RNA運(yùn)動(dòng)中。第68頁(yè)/共308頁(yè)FIGURE1–9Rankingofbiologicalphosphatecompoundsbystandardfreeenergiesofhydrolysis.

按水解反應(yīng)的標(biāo)準(zhǔn)自由能排列的生物磷酸化合物Thisshowstheflowofphosphorylgroupsfromhigh-energyphosphoryldonorsviaATPtoacceptormolecules(suchasglucoseandglycerol)toformtheirlow-energyphosphatederivatives.顯示了磷?；鶊F(tuán)的流向。通過(guò)ATP從高能磷酸供體到受體分子，以形成它們的低能磷酸衍生物。Thisflowofphosphorylgroups,catalyzedbykinases,proceedswithanoveralllossoffreeenergyunderintracellularconditions.HydrolysisoflowenergyphosphatecompoundsreleasesPi,whichhasanevenlowerphosphorylgrouptransferpotential.這股磷酰基團(tuán)流，受激酶的催化，伴隨著在胞內(nèi)條件下的自由能損失。低能臉?biāo)慊衔锏乃忉尫帕姿?，它有更低的磷?；鶊F(tuán)轉(zhuǎn)移勢(shì)能。第69頁(yè)/共308頁(yè)磷酸肌酸高能化合物低能化合物甘油磷酸第70頁(yè)/共308頁(yè)OnemorechemicalfeatureofATPiscrucialtoitsroleinmetabolism:ATP的另一個(gè)化學(xué)特性對(duì)于它在代謝中的作用是很關(guān)鍵的：ATP在動(dòng)力學(xué)上是穩(wěn)定的，因?yàn)榱姿狒I無(wú)催化斷裂需要巨大的活化能(200-400kJ/mol),ATP無(wú)法自發(fā)地將磷酸基團(tuán)轉(zhuǎn)移到水中或細(xì)胞中數(shù)百種其他潛在受體上。。僅在特定酶降低反應(yīng)活化能后，ATP上的磷?；拍茼樌D(zhuǎn)移。細(xì)胞通過(guò)調(diào)控作用于ATP上的不同的酶來(lái)調(diào)控ATP攜帶的能量在胞內(nèi)的分布。第71頁(yè)/共308頁(yè)1.2.4ATPDonatesPhosphoryl,Pyrophosphoryl,andAdenylylGroups

ATP提供磷酰、焦磷酰和腺苷?；鶊F(tuán)AnyofthethreePatoms(α,,or)mayserveastheelectrophilictargetfornucleophilicattack—inthiscase,bythelabelednucleophileR-18O:.Thenucleophilemaybeanalcohol(ROH),acarboxylgroup(RCOO-),oraphosphoanhydride(anucleosidemono-ordiphosphate,forexample).(a)Whentheoxygenofthenucleophileattacksthe

position,thebridgeoxygenoftheproductislabeled,indicatingthatthegrouptransferredfromATPisaphosphoryl(-PO32－),notaphosphate(-OPO32－).ATP轉(zhuǎn)移的官能團(tuán)是磷?；鶊F(tuán)，不是磷酸基團(tuán)(b)Attackonthe

positiondisplacesAMPandleadstothetransferofapyrophosphoryl(notpyrophosphate)grouptothenucleophile.焦磷?；鶊F(tuán)轉(zhuǎn)移到親核試劑上，不是焦磷酸。(c)AttackonthepositiondisplacesPPiandtransferstheadenylylgrouptothenucleophile.取代了PPi，并將核苷酸基團(tuán)轉(zhuǎn)移到親核試劑上第72頁(yè)/共308頁(yè)FIGURE1–10NucleophilicdisplacementreactionsofATP.ATP的親核取代反應(yīng)第73頁(yè)/共308頁(yè)1.2.5AssemblyofInformationalMacromoleculesRequiresEnergy

信息大分子的裝配需要能量Whensimpleprecursorsareassembledintohighmolecularweightpolymerswithdefinedsequences(DNA,RNA,proteins)，energyisrequiredbothforthecondensationofmonomericunitsandforthecreationoforderedsequences.單體的縮合和有序序列的產(chǎn)生都需要能量。TheprecursorsforDNAandRNAsynthesisarenucleosidetriphosphates,andpolymerizationisaccompaniedbycleavageofthephosphoanhydridelinkage磷酸酐鍵betweentheαand

phosphates,withthereleaseofPPi(Fig.1–11).第74頁(yè)/共308頁(yè)FIGURE1–11NucleosidetriphosphatesinRNAsynthesis.在RNA合成中的核苷三磷酸Witheachnucleosidemonophosphateaddedtothegrowingchain,onePPiisreleasedandhydrolyzedtotwoPi.Thehydrolysisoftwophosphoanhydridebondsforeachnucleotideaddedpro