課件-生物化學(xué)3-oxidative氧化磷酸化

OxidativeZhang: :1

MitochondrialStructureandEnergyElectronOxidativeShuttlingElectronCarriersintotherespiratory2TCAcycleiscoupledtoelectrontransportandoxidativephosphorylation3Oxidative（氧化磷酸化）isthemostcommonenergy-yieldingmetabolisminaerobic（好氧）organisms，inwhichtheenergyofoxidationdrivestheof4Wheredoesthisprocess Mitochondrialoutermembrane：porous（透性innermembrane：muchhighlyfoldedintocristae（嵴intermembranespace（膜間隙Mostvertebrate（脊椎動物6containseveralhundredoutermitochondrialmembrane permeabletosmallmoleculesMr5,000andions（離子）movefreelythroughporins（孔蛋白）.innermembrane impermeabletomostsmallmoleculesandions,includingprotons(H)------onlythroughspecifictransporterscomponentsoftherespiratorychainandtheATP7respiratoryproteinsareboundtotheinnerthedensityofcristaecorrespondstotherespiratoryactivityofacellQ：Whichonehasmorecristae，livercellsorheartcells？899Twoelectronproteinelectroncarriers--embeddedwithintheinnerfourcomplexesI,II,III,Processesoccurringinsidethemitochondrialpyruvateoxidation( fattyacidoxidation（脂肪酸氧化）aminoacidmetabolism（尿素循環(huán)）citricacidcycle（三 Energycellmotility,musclecontraction,thespecifictransportsubstancesacrossATPisproducedinthecellfromADPasaresultofthreetypesofphosphorylations–substrate-levelphosphorylations（底物水平磷酸化）occurwhena"high-energyphosphatemoleculetransfersphosphatetoADPtoformATPoxidativephosphorylation（氧化磷酸化，線粒體photosyntheticphosphorylation（光合磷酸化）(inplantsorsomebacteria)substrate-level酸激oxidativephotosyntheticphosphorylation（plant）ElectronBiologicaloxidationsgeneratereducedelectronNADH,?Reducedelectroncarriersdonatetheirelectronsacceptormolecules ereoxidizedintheTheacceptormoleculesare-Theplaceinthecellwhereelectronsgeneratedbyoxidationaretransferred.PassageoftheelectronsthroughthesystemgeneratespotentialenergythatisusedtomakeATPinoxidativesomeelectroncarriersinComplexI(orNADHNADHisgeneratedbynumerousNADHisreoxidizedtoNAD+bycomplexNADHdehydrogenasecontainsflavinmononucleotideNADH+H++FMN<=>NAD++ComplexIcontainsabout42differentpolypeptideThefirstproton4H+/2epassedfromNADHtoComplexI(orNADHAcceptse-from NADHcanonlyin2e-transfer2 16-7Fe-S

4protonsComplexII(succinate-CoenzymeQ isnotinthepathtraveledbyelectronsfromComplexBothcomplexesIandIIdonatetheirelectronstothesameacceptor,coenzymeQcontainsiron-sulfurproteins,participateinelectronComplexIII(orCoQ-cytochromec containsadiversityofelectroncarryingincludecytochromeb,ironsulfurcenters,andcytochromeC1. ThesecondprotonpumpCytochromes—areproteins,absorptionofvisiblelight（可見光Eachtypeofcytochromeinitsreduced(Fe2+)statehasthreeabsorptionbandsinthevisiblerange.Cytochromesareagroupofredorbrown亞鐵血紅cyclicstructure,consistsoffourfive-membered,nitrogen-containingoesmalloeTheamiTheothercytochromesareintegralmembraneexceedinglydifficulttodissociatefromthemembrane-------lessisknownabouttheirComplexIVorcytochromecoxidase細(xì)胞色素氧化酶ccontainscytochromesaandcittakeselectronsfromThethirdprotonDeterminingtheSequenceofRespiratoryElectronCarriersstandardreductionpotential,E0’標(biāo)準(zhǔn)還InhibitorsofelectronOxidativeisaprocesswheretheenergyofbiologicaloxidationis yconvertedtothechemicalenergyofATP.ThecouplingofelectrontransportandATP ATP合成部ComplexV(ATPsynthase,FoF1complex).locatedoninnermitochondrialatopknob---F1(projectsintothemitochondrialmatrix,containsthreethebase---Fo(intheinnermitochondrialmembrane)astalk---joinstheknobtotheChemiosmoticChemicalcoupling (化學(xué)偶聯(lián)假說1953,EdwardConformationalcouplinghypothesis（結(jié)構(gòu)偶聯(lián)假說 PaulChemiosmotichypothesis（化學(xué)滲透假說）1978,Nobel1961,PeterMitc ,explainshowATPissynthesizedbymitochondriaasaresultofprotonspumpedduringETS.ChemiosmotichypothesismovementofelectronsthroughETS(theelectrontransportsystem)protonstobepumpedfromthemitochondrialmatrixtotheintermembranespacethedifferenceinprovidestheenergysourceformakingATPinthemitochondrionEvidencesupportingthechemiosmoticcouplingMitochondriapumpprotonsandestablishapHacrosstheirinnerOxidativephosphorylationrequiresanintactAgentsthatuncoupleETSfromoxidativephosphorylationdissipatetheprotongradient Binding-change

Paul1997Rotationalcatalysis（旋轉(zhuǎn)催化機制MovementoftheprotonsthroughFocomplexcausesittoF1ATPsynthaseasarotaryenginedrivingthesynthesisofATP.(p357)F1βsubunitcontainsthreebindingsitesforATPorADP+Tsite(Tight):bindtoStightly,havecatalyticLsite(Loose):bindtoSloosely，havenocatalyticOsite(Open)：bindtoSwithlowTheprotonmotivation------energyreleasedbyFO------γsubunitrotationP/OTheefficiencyofoxidativetheamountofATPmadeversustheamountofoxygenconsumed—x(P/Oratio)themoleculesofATPmadeperpairofelectronscarriedtheelectrontransport(P/2e-ratio)thebalancedequationforthemitochondrialoxidationofNADH:complexIfromNADH:about(10/4=2.5)complexII(FAD'selectrons):about 10(NADH)/6(succinate) 3 thesurplusonemaybeusedfortransportingATP,ADP,

2.5Adeninenucleotideandphosphatetranslocases嘌呤核苷酸 磷酸轉(zhuǎn)運ShuttlingElectronCarriersintothetheinnermembraneisnotpermeabletoHowcantheNADHgeneratedbyglycolysisinthecytosolbereoxidizedtoNAD+byO2viatherespiratorychain?Glycerol-3-Pshuttlesystem(甘油-3-磷酸穿梭途徑）malate/aspartateshuttlesystem（蘋果酸-天冬氨酸穿梭途徑）骨骼肌和IntheskeletalmuscleandbrainNote:theshuttletransferselectronsfromNADHultima makeFADH2TransferselectronstoCoQbypassingcomplex 胞甘油-3-磷酸脫氫甘油-3-

磷酸二線粒甘油-3-磷酸脫氫心、肝malate/aspartateshuttlesystem（蘋果酸-天冬氨酸穿梭途徑）particularlyactiveinliver,kidneyandheart2.5ATPsperpairofelectronsfrom 草酰乙草酰乙谷草轉(zhuǎn)氨 谷草轉(zhuǎn)氨Substrates：ADP,Pi,O2,oxidizableRespirationistightlycoupledtothesynthesisofATPsynthesis ydependentoncontinuedelectronflowfromtoATPisconsumedathighaccumulationofstimulatesBiologicalensuresthatsubstrateswillnotbeoxidizedtheirutilizationiscontrolledbythephysiologicalneedforRespirationdependsonADPasasubstrateforenergy-generating

energy Additionofanoxidizablesubstratehasasmalleffectontherespirationrate.ADPisadded,however,oxygenuptakeproceedsatanenhancedrateuntilalloftheaddedADPhasbeenconvertedtoATP,andthenoxygenuptakereturnstothebasalADPis氧化磷酸化影響 Chemicaluncouplers:dissipatetheprotonDNP（2，4- 酚 （IntermembraneLow

HighHigh

DNP（2，4- 酚permeabilizetheinnermitochondrialmembranetodestroytheprotonuncoupletheETSfromtheoxidativephosphorylationChemicalelectronselectronscontinuetopassthroughETSreduceoxygenwater,butATPisnotActionofThermogenin（產(chǎn)熱素BrownfatAspecializedtypeofadiposeRichinOxidizeFAsforheatproductionratherthaninhibitorsofoxidativephosphorylation（氧化磷酸化抑制劑ionophores（離子載體抑制劑）：脂溶性物 纈氨霉素 短桿菌

轉(zhuǎn)運陽離子到基質(zhì)中時消耗了自由能，降低了質(zhì)子動力，抑制ATP的形InhibitorsofelectronATP–glycolysisorTCA--substrate-level ElectronsstoredinNADHandFADH2,are