Oxidative Phosphorylation - Wikipedia, The Free Encyclopedia PDF

6/17/2016
OxidativephosphorylationWikipedia,thefreeencyclopedia
Oxidativephosphorylation
FromWikipedia,thefreeencyclopedia
Oxidativephosphorylation(orOXPHOSin
short)isthemetabolicpathwayinwhichcells
useenzymestooxidizenutrients,thereby
releasingenergywhichisusedtoreformATP.
Inmosteukaryotes,thistakesplaceinside
mitochondria.Almostallaerobicorganisms
carryoutoxidativephosphorylation.This
pathwayisprobablysopervasivebecauseitisa
highlyefficientwayofreleasingenergy,
comparedtoalternativefermentationprocesses
suchasanaerobicglycolysis.
Duringoxidativephosphorylation,electronsare
transferredfromelectrondonorstoelectron
acceptorssuchasoxygen,inredoxreactions.
Theseredoxreactionsreleaseenergy,whichis
usedtoformATP.Ineukaryotes,theseredox
reactionsarecarriedoutbyaseriesofprotein
complexeswithintheinnermembraneofthe
cell'smitochondria,whereas,inprokaryotes,
theseproteinsarelocatedinthecells'
intermembranespace.Theselinkedsetsof
proteinsarecalledelectrontransportchains.In
eukaryotes,fivemainproteincomplexesare
involved,whereasinprokaryotesmany
differentenzymesarepresent,usingavariety
ofelectrondonorsandacceptors.
Theelectrontransportchaininthecellisthesiteofoxidative
phosphorylationinprokaryotes.TheNADHandsuccinategenerated
inthecitricacidcycleareoxidized,releasingenergytopowerthe
ATPsynthase.
Theenergyreleasedbyelectronsflowingthroughthiselectrontransportchainisusedtotransportprotonsacross
theinnermitochondrialmembrane,inaprocesscalledelectrontransport.Thisgeneratespotentialenergyinthe
formofapHgradientandanelectricalpotentialacrossthismembrane.Thisstoreofenergyistappedbyallowing
protonstoflowbackacrossthemembraneanddownthisgradient,throughalargeenzymecalledATPsynthase
thisprocessisknownaschemiosmosis.ThisenzymeusesthisenergytogenerateATPfromadenosinediphosphate
(ADP),inaphosphorylationreaction.Thisreactionisdrivenbytheprotonflow,whichforcestherotationofapart
oftheenzymetheATPsynthaseisarotarymechanicalmotor.
Althoughoxidativephosphorylationisavitalpartofmetabolism,itproducesreactiveoxygenspeciessuchas
superoxideandhydrogenperoxide,whichleadtopropagationoffreeradicals,damagingcellsandcontributingto
diseaseand,possibly,aging(senescence).Theenzymescarryingoutthismetabolicpathwayarealsothetargetof
manydrugsandpoisonsthatinhibittheiractivities.
Contents
1 Overviewofenergytransferbychemiosmosis
2 Electronandprotontransfermolecules
3 Eukaryoticelectrontransportchains
https://en.wikipedia.org/wiki/Oxidative_phosphorylation
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3 Eukaryoticelectrontransportchains
3.1 NADHcoenzymeQoxidoreductase(complexI)
3.2 SuccinateQoxidoreductase(complexII)
3.3 ElectrontransferflavoproteinQoxidoreductase
3.4 Qcytochromecoxidoreductase(complexIII)
3.5 Cytochromecoxidase(complexIV)
3.6 Alternativereductasesandoxidases
3.7 Organizationofcomplexes
4 Prokaryoticelectrontransportchains
5 ATPsynthase(complexV)
6 Reactiveoxygenspecies
7 Inhibitors
8 History
9 Seealso
10 Notes
11 References
12 Furtherreading
12.1 Introductory
12.2 Advanced
13 Externallinks
13.1 Generalresources
13.2 Structuralresources
Overviewofenergytransferbychemiosmosis
Oxidativephosphorylationworksbyusingenergyreleasingchemicalreactionstodriveenergyrequiringreactions:
Thetwosetsofreactionsaresaidtobecoupled.Thismeansonecannotoccurwithouttheother.Theflowof
electronsthroughtheelectrontransportchain,fromelectrondonorssuchasNADHtoelectronacceptorssuchas
oxygen,isanexergonicprocessitreleasesenergy,whereasthesynthesisofATPisanendergonicprocess,which
requiresaninputofenergy.BoththeelectrontransportchainandtheATPsynthaseareembeddedinamembrane,
andenergyistransferredfromelectrontransportchaintotheATPsynthasebymovementsofprotonsacrossthis
membrane,inaprocesscalledchemiosmosis.[1]Inpractice,thisislikeasimpleelectriccircuit,withacurrentof
protonsbeingdrivenfromthenegativeNsideofthemembranetothepositivePsidebytheprotonpumping
enzymesoftheelectrontransportchain.Theseenzymesarelikeabattery,astheyperformworktodrivecurrent
throughthecircuit.Themovementofprotonscreatesanelectrochemicalgradientacrossthemembrane,whichis
oftencalledtheprotonmotiveforce.Ithastwocomponents:adifferenceinprotonconcentration(aH+gradient,
pH)andadifferenceinelectricpotential,withtheNsidehavinganegativecharge.[2]
ATPsynthasereleasesthisstoredenergybycompletingthecircuitandallowingprotonstoflowdownthe
electrochemicalgradient,backtotheNsideofthemembrane.[3]Thiskineticenergydrivestherotationofpartof
theenzymesstructureandcouplesthismotiontothesynthesisofATP.
Thetwocomponentsoftheprotonmotiveforcearethermodynamicallyequivalent:Inmitochondria,thelargest
partofenergyisprovidedbythepotentialinalkaliphilebacteriatheelectricalenergyevenhastocompensatefora
counteractinginversepHdifference.Inversely,chloroplastsoperatemainlyonpH.However,theyalsorequirea
smallmembranepotentialforthekineticsofATPsynthesis.AtleastinthecaseofthefusobacteriumP.modestum
itdrivesthecounterrotationofsubunitsaandcoftheFOmotorofATPsynthase.[2]
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Theamountofenergyreleasedbyoxidativephosphorylationishigh,comparedwiththeamountproducedby
anaerobicfermentation.Glycolysisproducesonly2ATPmolecules,butsomewherebetween30and36ATPsare
producedbytheoxidativephosphorylationofthe10NADHand2succinatemoleculesmadebyconvertingone
moleculeofglucosetocarbondioxideandwater,[4]whileeachcycleofbetaoxidationofafattyacidyieldsabout
14ATPs.TheseATPyieldsaretheoreticalmaximumvaluesinpractice,someprotonsleakacrossthemembrane,
loweringtheyieldofATP.[5]
Electronandprotontransfermolecules
Theelectrontransportchaincarriesbothprotonsandelectrons,passing
electronsfromdonorstoacceptors,andtransportingprotonsacrossa
membrane.Theseprocessesusebothsolubleandproteinbound
transfermolecules.Inmitochondria,electronsaretransferredwithin
theintermembranespacebythewatersolubleelectrontransferprotein
cytochromec.[6]Thiscarriesonlyelectrons,andthesearetransferred
bythereductionandoxidationofanironatomthattheproteinholds
withinahemegroupinitsstructure.Cytochromecisalsofoundin
somebacteria,whereitislocatedwithintheperiplasmicspace.[7]
Withintheinnermitochondrialmembrane,thelipidsolubleelectron
carriercoenzymeQ10(Q)carriesbothelectronsandprotonsbya
redoxcycle.[8]Thissmallbenzoquinonemoleculeisveryhydrophobic,
soitdiffusesfreelywithinthemembrane.WhenQacceptstwo
electronsandtwoprotons,itbecomesreducedtotheubiquinolform
(QH2)whenQH2releasestwoelectronsandtwoprotons,itbecomesoxidizedbacktotheubiquinone(Q)form.
ReductionofcoenzymeQfromits
ubiquinoneform(Q)tothereduced
ubiquinolform(QH2).
Asaresult,iftwoenzymesarearrangedsothatQisreducedononesideofthemembraneandQH2oxidizedon
theother,ubiquinonewillcouplethesereactionsandshuttleprotonsacrossthemembrane.[9]Somebacterial
electrontransportchainsusedifferentquinones,suchasmenaquinone,inadditiontoubiquinone.[10]
Withinproteins,electronsaretransferredbetweenflavincofactors,[3][11]ironsulfurclusters,andcytochromes.
Thereareseveraltypesofironsulfurcluster.Thesimplestkindfoundintheelectrontransferchainconsistsoftwo
ironatomsjoinedbytwoatomsofinorganicsulfurthesearecalled[2Fe2S]clusters.Thesecondkind,called
[4Fe4S],containsacubeoffourironatomsandfoursulfuratoms.Eachironatomintheseclustersiscoordinated
byanadditionalaminoacid,usuallybythesulfuratomofcysteine.Metalioncofactorsundergoredoxreactions
withoutbindingorreleasingprotons,sointheelectrontransportchaintheyservesolelytotransportelectrons
throughproteins.Electronsmovequitelongdistancesthroughproteinsbyhoppingalongchainsofthese
cofactors.[12]Thisoccursbyquantumtunnelling,whichisrapidoverdistancesoflessthan1.4 109m.[13]
Eukaryoticelectrontransportchains
Manycatabolicbiochemicalprocesses,suchasglycolysis,thecitricacidcycle,andbetaoxidation,producethe
reducedcoenzymeNADH.Thiscoenzymecontainselectronsthathaveahightransferpotentialinotherwords,
theywillreleasealargeamountofenergyuponoxidation.However,thecelldoesnotreleasethisenergyallat
once,asthiswouldbeanuncontrollablereaction.Instead,theelectronsareremovedfromNADHandpassedto
oxygenthroughaseriesofenzymesthateachreleaseasmallamountoftheenergy.Thissetofenzymes,consisting
ofcomplexesIthroughIV,iscalledtheelectrontransportchainandisfoundintheinnermembraneofthe
mitochondrion.Succinateisalsooxidizedbytheelectrontransportchain,butfeedsintothepathwayatadifferent
point.
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Ineukaryotes,theenzymesinthiselectrontransportsystemusetheenergyreleasedfromtheoxidationofNADH
topumpprotonsacrosstheinnermembraneofthemitochondrion.Thiscausesprotonstobuildupinthe
intermembranespace,andgeneratesanelectrochemicalgradientacrossthemembrane.Theenergystoredinthis
potentialisthenusedbyATPsynthasetoproduceATP.Oxidativephosphorylationintheeukaryotic
mitochondrionisthebestunderstoodexampleofthisprocess.Themitochondrionispresentinalmostall
eukaryotes,withtheexceptionofanaerobicprotozoasuchasTrichomonasvaginalisthatinsteadreduceprotonsto
hydrogeninaremnantmitochondrioncalledahydrogenosome.[14]
Typicalrespiratoryenzymesandsubstratesineukaryotes.
Midpointpotential
Respiratoryenzyme
Redoxpair
NADHdehydrogenase
NAD+/NADH
0.32[15]
Succinatedehydrogenase
FMNorFAD/FMNH2orFADH2
0.20[15]
(Volts)
Cytochromebc1complex CoenzymeQ10ox/CoenzymeQ10red
+0.06[15]
Cytochromebc1complex
Cytochromebox/Cytochromebred
+0.12[15]
ComplexIV
Cytochromecox/Cytochromecred
+0.22[15]
ComplexIV
Cytochromeaox/Cytochromeared
+0.29[15]
ComplexIV
O2/HO
+0.82[15]
Conditions:pH=7[15]
NADHcoenzymeQoxidoreductase(complexI)
NADHcoenzymeQoxidoreductase,alsoknownas
NADHdehydrogenaseorcomplexI,isthefirstprotein
intheelectrontransportchain.[16]ComplexIisagiant
enzymewiththemammaliancomplexIhaving46
subunitsandamolecularmassofabout1,000
kilodaltons(kDa).[17]Thestructureisknownindetail
onlyfromabacterium[18][19]inmostorganismsthe
complexresemblesabootwithalarge"ball"poking
outfromthemembraneintothemitochondrion.[20][21]
Thegenesthatencodetheindividualproteinsare
containedinboththecellnucleusandthe
mitochondrialgenome,asisthecaseformany
enzymespresentinthemitochondrion.
Thereactionthatiscatalyzedbythisenzymeisthetwo
electronoxidationofNADHbycoenzymeQ10or
ubiquinone(representedasQintheequationbelow),a
lipidsolublequinonethatisfoundinthe
mitochondrionmembrane:
ComplexIorNADHQoxidoreductase.Theabbreviations
arediscussedinthetext.Inalldiagramsofrespiratory
complexesinthisarticle,thematrixisatthebottom,with
theintermembranespaceabove.
(1)
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Thestartofthereaction,andindeedoftheentireelectronchain,isthebindingofaNADHmoleculetocomplexI
andthedonationoftwoelectrons.TheelectronsentercomplexIviaaprostheticgroupattachedtothecomplex,
flavinmononucleotide(FMN).TheadditionofelectronstoFMNconvertsittoitsreducedform,FMNH2.The
electronsarethentransferredthroughaseriesofironsulfurclusters:thesecondkindofprostheticgrouppresentin
thecomplex.[18]Thereareboth[2Fe2S]and[4Fe4S]ironsulfurclustersincomplexI.
Astheelectronspassthroughthiscomplex,fourprotonsarepumpedfromthematrixintotheintermembrane
space.Exactlyhowthisoccursisunclear,butitseemstoinvolveconformationalchangesincomplexIthatcause
theproteintobindprotonsontheNsideofthemembraneandreleasethemonthePsideofthemembrane.[22]
Finally,theelectronsaretransferredfromthechainofironsulfurclusterstoaubiquinonemoleculeinthe
membrane.[16]Reductionofubiquinonealsocontributestothegenerationofaprotongradient,astwoprotonsare
takenupfromthematrixasitisreducedtoubiquinol(QH2).
SuccinateQoxidoreductase(complexII)
SuccinateQoxidoreductase,alsoknownascomplexIIorsuccinate
dehydrogenase,isasecondentrypointtotheelectrontransport
chain.[23]Itisunusualbecauseitistheonlyenzymethatispartofboth
thecitricacidcycleandtheelectrontransportchain.ComplexII
consistsoffourproteinsubunitsandcontainsaboundflavinadenine
dinucleotide(FAD)cofactor,ironsulfurclusters,andahemegroup
thatdoesnotparticipateinelectrontransfertocoenzymeQ,butis
believedtobeimportantindecreasingproductionofreactiveoxygen
species.[24][25]Itoxidizessuccinatetofumarateandreduces
ubiquinone.Asthisreactionreleaseslessenergythantheoxidationof
NADH,complexIIdoesnottransportprotonsacrossthemembrane
anddoesnotcontributetotheprotongradient.
(2)
ComplexII:SuccinateQoxidoreductase.
Insomeeukaryotes,suchastheparasiticwormAscarissuum,an
enzymesimilartocomplexII,fumaratereductase(menaquinol:fumarateoxidoreductase,orQFR),operatesin
reversetooxidizeubiquinolandreducefumarate.Thisallowsthewormtosurviveintheanaerobicenvironmentof
thelargeintestine,carryingoutanaerobicoxidativephosphorylationwithfumarateastheelectronacceptor.[26]
AnotherunconventionalfunctionofcomplexIIisseeninthemalariaparasitePlasmodiumfalciparum.Here,the
reversedactionofcomplexIIasanoxidaseisimportantinregeneratingubiquinol,whichtheparasiteusesinan
unusualformofpyrimidinebiosynthesis.[27]
ElectrontransferflavoproteinQoxidoreductase
Electrontransferflavoproteinubiquinoneoxidoreductase(ETFQoxidoreductase),alsoknownaselectron
transferringflavoproteindehydrogenase,isathirdentrypointtotheelectrontransportchain.Itisanenzymethat
acceptselectronsfromelectrontransferringflavoproteininthemitochondrialmatrix,andusestheseelectronsto
reduceubiquinone.[28]Thisenzymecontainsaflavinanda[4Fe4S]cluster,but,unliketheotherrespiratory
complexes,itattachestothesurfaceofthemembraneanddoesnotcrossthelipidbilayer.[29]
(3)
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Inmammals,thismetabolicpathwayisimportantinbetaoxidationoffattyacidsandcatabolismofaminoacids
andcholine,asitacceptselectronsfrommultipleacetylCoAdehydrogenases.[30][31]Inplants,ETFQ
oxidoreductaseisalsoimportantinthemetabolicresponsesthatallowsurvivalinextendedperiodsofdarkness.[32]
Qcytochromecoxidoreductase(complexIII)
Qcytochromecoxidoreductaseisalso
knownascytochromecreductase,
cytochromebc1complex,orsimplycomplex
III.[33][34]Inmammals,thisenzymeisa
dimer,witheachsubunitcomplex
containing11proteinsubunits,an[2Fe2S]
ironsulfurclusterandthreecytochromes:
onecytochromec1andtwob
cytochromes.[35]Acytochromeisakindof
electrontransferringproteinthatcontainsat
leastonehemegroup.Theironatomsinside
complexIIIshemegroupsalternate
betweenareducedferrous(+2)andoxidized
ferric(+3)stateastheelectronsare
transferredthroughtheprotein.
ThetwoelectrontransferstepsincomplexIII:Qcytochromec
oxidoreductase.Aftereachstep,Q(intheupperpartofthefigure)leaves
theenzyme.
ThereactioncatalyzedbycomplexIIIistheoxidationofonemoleculeofubiquinolandthereductionoftwo
moleculesofcytochromec,ahemeproteinlooselyassociatedwiththemitochondrion.UnlikecoenzymeQ,which
carriestwoelectrons,cytochromeccarriesonlyoneelectron.
(4)
AsonlyoneoftheelectronscanbetransferredfromtheQH2donortoacytochromecacceptoratatime,the
reactionmechanismofcomplexIIIismoreelaboratethanthoseoftheotherrespiratorycomplexes,andoccursin
twostepscalledtheQcycle.[36]Inthefirststep,theenzymebindsthreesubstrates,first,QH2,whichisthen
oxidized,withoneelectronbeingpassedtothesecondsubstrate,cytochromec.Thetwoprotonsreleasedfrom
QH2passintotheintermembranespace.ThethirdsubstrateisQ,whichacceptsthesecondelectronfromtheQH2
andisreducedtoQ.,whichistheubisemiquinonefreeradical.Thefirsttwosubstratesarereleased,butthis
ubisemiquinoneintermediateremainsbound.Inthesecondstep,asecondmoleculeofQH2isboundandagain
passesitsfirstelectrontoacytochromecacceptor.Thesecondelectronispassedtotheboundubisemiquinone,
reducingittoQH2asitgainstwoprotonsfromthemitochondrialmatrix.ThisQH2isthenreleasedfromthe
enzyme.[37]
AscoenzymeQisreducedtoubiquinolontheinnersideofthemembraneandoxidizedtoubiquinoneontheother,
anettransferofprotonsacrossthemembraneoccurs,addingtotheprotongradient.[3]Therathercomplextwostep
mechanismbywhichthisoccursisimportant,asitincreasestheefficiencyofprotontransfer.If,insteadoftheQ
cycle,onemoleculeofQH2wereusedtodirectlyreducetwomoleculesofcytochromec,theefficiencywouldbe
halved,withonlyoneprotontransferredpercytochromecreduced.[3]
Cytochromecoxidase(complexIV)
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Cytochromecoxidase,alsoknownascomplexIV,isthefinalprotein
complexintheelectrontransportchain.[38]Themammalianenzymehasan
extremelycomplicatedstructureandcontains13subunits,twoheme
groups,aswellasmultiplemetalioncofactorsinall,threeatomsof
copper,oneofmagnesiumandoneofzinc.[39]
Thisenzymemediatesthefinalreactionintheelectrontransportchainand
transferselectronstooxygen,whilepumpingprotonsacrossthe
membrane.[40]Thefinalelectronacceptoroxygen,whichisalsocalledthe
terminalelectronacceptor,isreducedtowaterinthisstep.Boththedirect
pumpingofprotonsandtheconsumptionofmatrixprotonsinthereduction
ofoxygencontributetotheprotongradient.Thereactioncatalyzedisthe
oxidationofcytochromecandthereductionofoxygen:
ComplexIV:cytochromecoxidase.
(5)
Alternativereductasesandoxidases
Manyeukaryoticorganismshaveelectrontransportchainsthatdifferfromthemuchstudiedmammalianenzymes
describedabove.Forexample,plantshavealternativeNADHoxidases,whichoxidizeNADHinthecytosolrather
thaninthemitochondrialmatrix,andpasstheseelectronstotheubiquinonepool.[41]Theseenzymesdonot
transportprotons,and,therefore,reduceubiquinonewithoutalteringtheelectrochemicalgradientacrosstheinner
membrane.[42]
Anotherexampleofadivergentelectrontransportchainisthealternativeoxidase,whichisfoundinplants,aswell
assomefungi,protists,andpossiblysomeanimals.[43][44]Thisenzymetransferselectronsdirectlyfromubiquinol
tooxygen.[45]
TheelectrontransportpathwaysproducedbythesealternativeNADHandubiquinoneoxidaseshavelowerATP
yieldsthanthefullpathway.Theadvantagesproducedbyashortenedpathwayarenotentirelyclear.However,the
alternativeoxidaseisproducedinresponsetostressessuchascold,reactiveoxygenspecies,andinfectionby
pathogens,aswellasotherfactorsthatinhibitthefullelectrontransportchain.[46][47]Alternativepathwaysmight,
therefore,enhanceanorganisms'resistancetoinjury,byreducingoxidativestress.[48]
Organizationofcomplexes
Theoriginalmodelforhowtherespiratorychaincomplexesareorganizedwasthattheydiffusefreelyand
independentlyinthemitochondrialmembrane.[49]However,recentdatasuggestthatthecomplexesmightform
higherorderstructurescalledsupercomplexesor"respirasomes."[50]Inthismodel,thevariouscomplexesexistas
organizedsetsofinteractingenzymes.[51]Theseassociationsmightallowchannelingofsubstratesbetweenthe
variousenzymecomplexes,increasingtherateandefficiencyofelectrontransfer.[52]Withinsuchmammalian
supercomplexes,somecomponentswouldbepresentinhigheramountsthanothers,withsomedatasuggestinga
ratiobetweencomplexesI/II/III/IVandtheATPsynthaseofapproximately1:1:3:7:4.[53]However,thedebateover
thissupercomplexhypothesisisnotcompletelyresolved,assomedatadonotappeartofitwiththismodel.[17][54]
Prokaryoticelectrontransportchains
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Incontrasttothegeneralsimilarityinstructureandfunctionoftheelectrontransportchainsineukaryotes,bacteria
andarchaeapossessalargevarietyofelectrontransferenzymes.Theseuseanequallywidesetofchemicalsas
substrates.[55]Incommonwitheukaryotes,prokaryoticelectrontransportusestheenergyreleasedfromthe
oxidationofasubstratetopumpionsacrossamembraneandgenerateanelectrochemicalgradient.Inthebacteria,
oxidativephosphorylationinEscherichiacoliisunderstoodinmostdetail,whilearchaealsystemsareatpresent
poorlyunderstood.[56]
Themaindifferencebetweeneukaryoticandprokaryoticoxidativephosphorylationisthatbacteriaandarchaeause
manydifferentsubstancestodonateoracceptelectrons.Thisallowsprokaryotestogrowunderawidevarietyof
environmentalconditions.[57]InE.coli,forexample,oxidativephosphorylationcanbedrivenbyalargenumberof
pairsofreducingagentsandoxidizingagents,whicharelistedbelow.Themidpointpotentialofachemical
measureshowmuchenergyisreleasedwhenitisoxidizedorreduced,withreducingagentshavingnegative
potentialsandoxidizingagentspositivepotentials.
RespiratoryenzymesandsubstratesinE.coli.[58]
Midpointpotential
Respiratoryenzyme
Redoxpair
(Volts)
Formatedehydrogenase
Bicarbonate/Formate
0.43
Hydrogenase
Proton/Hydrogen
0.42
NADHdehydrogenase
NAD+/NADH
0.32
Glycerol3phosphatedehydrogenase DHAP/Gly3P
0.19
Pyruvateoxidase
Acetate+Carbondioxide/Pyruvate
Lactatedehydrogenase
Pyruvate/Lactate
Daminoaciddehydrogenase
2oxoacid+ammonia/Daminoacid
Glucosedehydrogenase
Gluconate/Glucose
0.14
Succinatedehydrogenase
Fumarate/Succinate
+0.03
Ubiquinoloxidase
Oxygen/Water
+0.82
Nitratereductase
Nitrate/Nitrite
+0.42
Nitritereductase
Nitrite/Ammonia
+0.36
Dimethylsulfoxidereductase
DMSO/DMS
+0.16
TrimethylamineNoxidereductase
TMAO/TMA
+0.13
Fumaratereductase
Fumarate/Succinate
+0.03
0.19
?
Asshownabove,E.colicangrowwithreducingagentssuchasformate,hydrogen,orlactateaselectrondonors,
andnitrate,DMSO,oroxygenasacceptors.[57]Thelargerthedifferenceinmidpointpotentialbetweenan
oxidizingandreducingagent,themoreenergyisreleasedwhentheyreact.Outofthesecompounds,the
succinate/fumaratepairisunusual,asitsmidpointpotentialisclosetozero.Succinatecanthereforebeoxidizedto
fumarateifastrongoxidizingagentsuchasoxygenisavailable,orfumaratecanbereducedtosuccinateusinga
strongreducingagentsuchasformate.Thesealternativereactionsarecatalyzedbysuccinatedehydrogenaseand
fumaratereductase,respectively.[59]
Someprokaryotesuseredoxpairsthathaveonlyasmalldifferenceinmidpointpotential.Forexample,nitrifying
bacteriasuchasNitrobacteroxidizenitritetonitrate,donatingtheelectronstooxygen.Thesmallamountof
energyreleasedinthisreactionisenoughtopumpprotonsandgenerateATP,butnotenoughtoproduceNADHor
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NADPHdirectlyforuseinanabolism.[60]Thisproblemissolvedbyusinganitriteoxidoreductasetoproduce
enoughprotonmotiveforcetorunpartoftheelectrontransportchaininreverse,causingcomplexItogenerate
NADH.[61][62]
Prokaryotescontroltheiruseoftheseelectrondonorsandacceptorsbyvaryingwhichenzymesareproduced,in
responsetoenvironmentalconditions.[63]Thisflexibilityispossiblebecausedifferentoxidasesandreductasesuse
thesameubiquinonepool.Thisallowsmanycombinationsofenzymestofunctiontogether,linkedbythecommon
ubiquinolintermediate.[58]Theserespiratorychainsthereforehaveamodulardesign,witheasilyinterchangeable
setsofenzymesystems.
Inadditiontothismetabolicdiversity,prokaryotesalsopossessarangeofisozymesdifferentenzymesthat
catalyzethesamereaction.Forexample,inE.coli,therearetwodifferenttypesofubiquinoloxidaseusingoxygen
asanelectronacceptor.Underhighlyaerobicconditions,thecellusesanoxidasewithalowaffinityforoxygen
thatcantransporttwoprotonsperelectron.However,iflevelsofoxygenfall,theyswitchtoanoxidasethat
transfersonlyoneprotonperelectron,buthasahighaffinityforoxygen.[64]
ATPsynthase(complexV)
ATPsynthase,alsocalledcomplexV,isthefinalenzymeintheoxidativephosphorylationpathway.Thisenzyme
isfoundinallformsoflifeandfunctionsinthesamewayinbothprokaryotesandeukaryotes.[65]Theenzymeuses
theenergystoredinaprotongradientacrossamembranetodrivethesynthesisofATPfromADPandphosphate
(Pi).EstimatesofthenumberofprotonsrequiredtosynthesizeoneATPhaverangedfromthreetofour,[66][67]with
somesuggestingcellscanvarythisratio,tosuitdifferentconditions.[68]
(7)
Thisphosphorylationreactionisanequilibrium,whichcanbeshiftedbyalteringtheprotonmotiveforce.Inthe
absenceofaprotonmotiveforce,theATPsynthasereactionwillrunfromrighttoleft,hydrolyzingATPand
pumpingprotonsoutofthematrixacrossthemembrane.However,whentheprotonmotiveforceishigh,the
reactionisforcedtorunintheoppositedirectionitproceedsfromlefttoright,allowingprotonstoflowdown
theirconcentrationgradientandturningADPintoATP.[65]Indeed,inthecloselyrelatedvacuolartypeH+
ATPases,thehydrolysisreactionisusedtoacidifycellularcompartments,bypumpingprotonsandhydrolysing
ATP.[69]
ATPsynthaseisamassiveproteincomplexwithamushroomlikeshape.Themammalianenzymecomplex
contains16subunitsandhasamassofapproximately600kilodaltons.[70]Theportionembeddedwithinthe
membraneiscalledFOandcontainsaringofcsubunitsandtheprotonchannel.Thestalkandtheballshaped
headpieceiscalledF1andisthesiteofATPsynthesis.TheballshapedcomplexattheendoftheF1portion
containssixproteinsoftwodifferentkinds(threesubunitsandthreesubunits),whereasthe"stalk"consistsof
oneprotein:thesubunit,withthetipofthestalkextendingintotheballofandsubunits.[71]Boththeand
subunitsbindnucleotides,butonlythesubunitscatalyzetheATPsynthesisreaction.Reachingalongthesideof
theF1portionandbackintothemembraneisalongrodlikesubunitthatanchorstheandsubunitsintothebase
oftheenzyme.
AsprotonscrossthemembranethroughthechannelinthebaseofATPsynthase,theFOprotondrivenmotor
rotates.[72]Rotationmightbecausedbychangesintheionizationofaminoacidsintheringofcsubunitscausing
electrostaticinteractionsthatpropeltheringofcsubunitspasttheprotonchannel.[73]Thisrotatingringinturn
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drivestherotationofthecentralaxle(thesubunitstalk)withintheandsubunits.Theandsubunitsare
preventedfromrotatingthemselvesbythesidearm,whichactsasastator.Thismovementofthetipofthe
subunitwithintheballofandsubunitsprovidestheenergyfortheactivesitesinthesubunitstoundergoa
cycleofmovementsthatproducesandthenreleasesATP.[74]
ThisATPsynthesisreactioniscalledthebindingchangemechanismand
involvestheactivesiteofasubunitcyclingbetweenthreestates.[75]In
the"open"state,ADPandphosphateentertheactivesite(showninbrown
inthediagram).Theproteinthenclosesuparoundthemoleculesandbinds
themlooselythe"loose"state(showninred).Theenzymethenchanges
shapeagainandforcesthesemoleculestogether,withtheactivesiteinthe
resulting"tight"state(showninpink)bindingthenewlyproducedATP
moleculewithveryhighaffinity.Finally,theactivesitecyclesbacktothe
openstate,releasingATPandbindingmoreADPandphosphate,readyfor
thenextcycle.
Insomebacteriaandarchaea,ATPsynthesisisdrivenbythemovementof
sodiumionsthroughthecellmembrane,ratherthanthemovementof
protons.[76][77]ArchaeasuchasMethanococcusalsocontaintheA1Ao
MechanismofATPsynthase.ATPis
showninred,ADPandphosphatein
pinkandtherotatingsubunitin
black.
synthase,aformoftheenzymethatcontainsadditionalproteinswithlittle
similarityinsequencetootherbacterialandeukaryoticATPsynthase
subunits.Itispossiblethat,insomespecies,theA1AoformoftheenzymeisaspecializedsodiumdrivenATP
synthase,[78]butthismightnotbetrueinallcases.[77]
Reactiveoxygenspecies
Molecularoxygenisanidealterminalelectronacceptorbecauseitisastrongoxidizingagent.Thereductionof
oxygendoesinvolvepotentiallyharmfulintermediates.[79]Althoughthetransferoffourelectronsandfourprotons
reducesoxygentowater,whichisharmless,transferofoneortwoelectronsproducessuperoxideorperoxide
anions,whicharedangerouslyreactive.
(7)
Thesereactiveoxygenspeciesandtheirreactionproducts,suchasthehydroxylradical,areveryharmfultocells,
astheyoxidizeproteinsandcausemutationsinDNA.Thiscellulardamagemightcontributetodiseaseandis
proposedasonecauseofaging.[80][81]
Thecytochromecoxidasecomplexishighlyefficientatreducingoxygentowater,anditreleasesveryfewpartly
reducedintermediateshoweversmallamountsofsuperoxideanionandperoxideareproducedbytheelectron
transportchain.[82]ParticularlyimportantisthereductionofcoenzymeQincomplexIII,asahighlyreactive
ubisemiquinonefreeradicalisformedasanintermediateintheQcycle.Thisunstablespeciescanleadtoelectron
"leakage"whenelectronstransferdirectlytooxygen,formingsuperoxide.[83]Astheproductionofreactiveoxygen
speciesbytheseprotonpumpingcomplexesisgreatestathighmembranepotentials,ithasbeenproposedthat
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mitochondriaregulatetheiractivitytomaintainthemembranepotentialwithinanarrowrangethatbalancesATP
productionagainstoxidantgeneration.[84]Forinstance,oxidantscanactivateuncouplingproteinsthatreduce
membranepotential.[85]
Tocounteractthesereactiveoxygenspecies,cellscontainnumerousantioxidantsystems,includingantioxidant
vitaminssuchasvitaminCandvitaminE,andantioxidantenzymessuchassuperoxidedismutase,catalase,and
peroxidases,[79]whichdetoxifythereactivespecies,limitingdamagetothecell.
Inhibitors
Thereareseveralwellknowndrugsandtoxinsthatinhibitoxidativephosphorylation.Althoughanyoneofthese
toxinsinhibitsonlyoneenzymeintheelectrontransportchain,inhibitionofanystepinthisprocesswillhaltthe
restoftheprocess.Forexample,ifoligomycininhibitsATPsynthase,protonscannotpassbackintothe
mitochondrion.[86]Asaresult,theprotonpumpsareunabletooperate,asthegradientbecomestoostrongforthem
toovercome.NADHisthennolongeroxidizedandthecitricacidcycleceasestooperatebecausethe
concentrationofNAD+fallsbelowtheconcentrationthattheseenzymescanuse.
Compounds
Use
Siteof
action
Cyanide
Carbonmonoxide
Complex
Poisons
Azide
IV
Hydrogensulfide
Oligomycin
Antibiotic
Complex
V
Effectonoxidativephosphorylation
Inhibittheelectrontransportchainbybindingmorestronglythan
oxygentotheFeCucenterincytochromecoxidase,preventingthe
reductionofoxygen.[87]
InhibitsATPsynthasebyblockingtheflowofprotonsthroughtheFo
subunit.[86]
Ionophoresthatdisrupttheprotongradientbycarryingprotonsacrossa
Poisons,
membrane.ThisionophoreuncouplesprotonpumpingfromATP
CCCP
Inner
weight
2,4Dinitrophenol
membrane synthesisbecauseitcarriesprotonsacrosstheinnermitochondrial
loss[N1]
membrane.[88]
PreventsthetransferofelectronsfromcomplexItoubiquinoneby
blockingtheubiquinonebindingsite.[89]
Rotenone
Pesticide ComplexI
Malonateand
oxaloacetate
Poisons
Complex
II
Competitiveinhibitorsofsuccinatedehydrogenase(complexII).[90]
AntimycinA
Piscicide
Complex
III
BindstotheQisiteofcytochromecreductase,therebyinhibitingthe
oxidationofubiquinol.
Notallinhibitorsofoxidativephosphorylationaretoxins.Inbrownadiposetissue,regulatedprotonchannels
calleduncouplingproteinscanuncouplerespirationfromATPsynthesis.[91]Thisrapidrespirationproducesheat,
andisparticularlyimportantasawayofmaintainingbodytemperatureforhibernatinganimals,althoughthese
proteinsmayalsohaveamoregeneralfunctionincells'responsestostress.[92]
History
Thefieldofoxidativephosphorylationbeganwiththereportin1906byArthurHardenofavitalroleforphosphate
incellularfermentation,butinitiallyonlysugarphosphateswereknowntobeinvolved.[93]However,intheearly
1940s,thelinkbetweentheoxidationofsugarsandthegenerationofATPwasfirmlyestablishedbyHerman
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Kalckar,[94]confirmingthecentralroleofATPinenergytransferthathadbeenproposedbyFritzAlbertLipmann
in1941.[95]Later,in1949,MorrisFriedkinandAlbertL.LehningerprovedthatthecoenzymeNADHlinked
metabolicpathwayssuchasthecitricacidcycleandthesynthesisofATP.[96]Thetermoxidativephosphorylation
wascoinedbyVolodymyrBelitserin1939.[97][98]
Foranothertwentyyears,themechanismbywhichATPisgeneratedremainedmysterious,withscientists
searchingforanelusive"highenergyintermediate"thatwouldlinkoxidationandphosphorylationreactions.[99]
ThispuzzlewassolvedbyPeterD.Mitchellwiththepublicationofthechemiosmotictheoryin1961.[100]Atfirst,
thisproposalwashighlycontroversial,butitwasslowlyacceptedandMitchellwasawardedaNobelprizein
1978.[101][102]Subsequentresearchconcentratedonpurifyingandcharacterizingtheenzymesinvolved,withmajor
contributionsbeingmadebyDavidE.Greenonthecomplexesoftheelectrontransportchain,aswellasEfraim
RackerontheATPsynthase.[103]AcriticalsteptowardssolvingthemechanismoftheATPsynthasewasprovided
byPaulD.Boyer,byhisdevelopmentin1973ofthe"bindingchange"mechanism,followedbyhisradical
proposalofrotationalcatalysisin1982.[75][104]Morerecentworkhasincludedstructuralstudiesontheenzymes
involvedinoxidativephosphorylationbyJohnE.Walker,withWalkerandBoyerbeingawardedaNobelPrizein
1997.[105]
Seealso
Respirometry
TIM/TOMComplex
Notes
1.DNPwasextensivelyusedasanantiobesitymedicationinthe1930sbutwasultimatelydiscontinuedduetoits
dangeroussideeffects.However,illicituseofthedrugforthispurposecontinuestoday.See2,4Dinitrophenol#Dieting
aidformoreinformation.
References
1.MitchellP,MoyleJ(1967)."Chemiosmotichypothesisofoxidativephosphorylation".Nature213(5072):1379.
Bibcode:1967Natur.213..137M.doi:10.1038/213137a0.PMID4291593.
2.DimrothP,KaimG,MattheyU(1January2000)."CrucialroleofthemembranepotentialforATPsynthesisbyF(1)F(o)
ATPsynthases".J.Exp.Biol.203(Pt1):519.PMID10600673.
3.SchultzBE,ChanSI(2001)."Structuresandprotonpumpingstrategiesofmitochondrialrespiratoryenzymes".AnnuRev
BiophysBiomolStruct30:2365.doi:10.1146/annurev.biophys.30.1.23.PMID11340051.
4.RichPR(2003)."ThemolecularmachineryofKeilin'srespiratorychain"(PDF).Biochem.Soc.Trans.31(Pt6):1095
105.doi:10.1042/bst0311095.PMID14641005.
5.PorterRK,BrandMD(1995)."MitochondrialprotonconductanceandH+/Oratioareindependentofelectrontransport
rateinisolatedhepatocytes".Biochem.J.310(Pt2)((Pt2)):37982.doi:10.1042/bj3100379.PMC1135905.
PMID7654171.
6.MathewsFS(1985)."Thestructure,functionandevolutionofcytochromes".Prog.Biophys.Mol.Biol.45(1):156.
doi:10.1016/00796107(85)900045.PMID3881803.
7.WoodPM(1983)."Whydoctypecytochromesexist?".FEBSLett.164(2):2236.doi:10.1016/00145793(83)802890.
PMID6317447.
8.CraneFL(1December2001)."BiochemicalfunctionsofcoenzymeQ10".JAmCollNutr20(6):5918.
doi:10.1080/07315724.2001.10719063.PMID11771674.
9.MitchellP(1979)."Keilin'srespiratorychainconceptanditschemiosmoticconsequences".Science206(4423):114859.
Bibcode:1979Sci...206.1148M.doi:10.1126/science.388618.PMID388618.
10.SballeB,PooleRK(1999)."Microbialubiquinones:multiplerolesinrespiration,generegulationandoxidativestress
management"(PDF).Microbiology(Reading,Engl.)145(8):181730.doi:10.1099/1350087214581817.
12/18
6/17/2016
management"(PDF).Microbiology(Reading,Engl.)145(8):181730.doi:10.1099/1350087214581817.
PMID10463148.
11.JohnsonDC,DeanDR,SmithAD,JohnsonMK(2005)."Structure,function,andformationofbiologicalironsulfur
clusters".Annu.Rev.Biochem.74:24781.doi:10.1146/annurev.biochem.74.082803.133518.PMID15952888.
12.PageCC,MoserCC,ChenX,DuttonPL(1999)."Naturalengineeringprinciplesofelectrontunnellinginbiological
oxidationreduction".Nature402(6757):4752.Bibcode:1999Natur.402...47P.doi:10.1038/46972.PMID10573417.
13.LeysD,ScruttonNS(2004)."Electricalcircuitryinbiology:emergingprinciplesfromproteinstructure".Curr.Opin.
Struct.Biol.14(6):6427.doi:10.1016/j.sbi.2004.10.002.PMID15582386.
14.BoxmaB,deGraafRM,vanderStaayGW,vanAlenTA,RicardG,GabaldnT,vanHoekAH,MoonvanderStaay
SY,KoopmanWJ,vanHellemondJJ,TielensAG,FriedrichT,VeenhuisM,HuynenMA,HacksteinJH(2005)."An
anaerobicmitochondrionthatproduceshydrogen".Nature434(7029):749.Bibcode:2005Natur.434...74B.
doi:10.1038/nature03343.PMID15744302.
15.MedicalCHEMISTRYCompendium.ByAndersOvergaardPedersenandHenningNielsen.AarhusUniversity.2008
16.HirstJ(2005)."EnergytransductionbyrespiratorycomplexIanevaluationofcurrentknowledge"(PDF).Biochem.Soc.
Trans.33(Pt3):5259.doi:10.1042/BST0330525.PMID15916556.
17.LenazG,FatoR,GenovaML,BergaminiC,BianchiC,BiondiA(2006)."MitochondrialComplexI:structuraland
functionalaspects".Biochim.Biophys.Acta1757(910):140620.doi:10.1016/j.bbabio.2006.05.007.PMID16828051.
18.SazanovLA,HinchliffeP(2006)."StructureofthehydrophilicdomainofrespiratorycomplexIfromThermus
thermophilus".Science311(5766):14306.Bibcode:2006Sci...311.1430S.doi:10.1126/science.1123809.
PMID16469879.
19.EfremovR.G.,BaradaranR.,&SazanovL.A.,(2010)ThearcdhitectureofrespiratorycomplexI,Nature465,441445
20.BaranovaEA,HoltPJ,SazanovLA(2007)."ProjectionstructureofthemembranedomainofEscherichiacolirespiratory
complexIat8Aresolution".J.Mol.Biol.366(1):14054.doi:10.1016/j.jmb.2006.11.026.PMID17157874.
21.FriedrichT,BttcherB(2004)."ThegrossstructureoftherespiratorycomplexI:aLegoSystem".Biochim.Biophys.
Acta1608(1):19.doi:10.1016/j.bbabio.2003.10.002.PMID14741580.
22.HirstJ(January2010)."TowardsthemolecularmechanismofrespiratorycomplexI".Biochem.J.425(2):32739.
doi:10.1042/BJ20091382.PMID20025615.
23.CecchiniG(2003)."FunctionandstructureofcomplexIIoftherespiratorychain".Annu.Rev.Biochem.72:77109.
doi:10.1146/annurev.biochem.72.121801.161700.PMID14527321.
24.YankovskayaV,HorsefieldR,TrnrothS,LunaChavezC,MiyoshiH,LgerC,ByrneB,CecchiniG,IwataS,etal.
(2003)."Architectureofsuccinatedehydrogenaseandreactiveoxygenspeciesgeneration".Science299(5607):7004.
Bibcode:2003Sci...299..700Y.doi:10.1126/science.1079605.PMID12560550.
25.HorsefieldR,IwataS,ByrneB(2004)."ComplexIIfromastructuralperspective".Curr.ProteinPept.Sci.5(2):107
18.doi:10.2174/1389203043486847.PMID15078221.
26.KitaK,HirawakeH,MiyaderaH,AminoH,TakeoS(2002)."RoleofcomplexIIinanaerobicrespirationoftheparasite
mitochondriafromAscarissuumandPlasmodiumfalciparum".Biochim.Biophys.Acta1553(12):12339.
doi:10.1016/S00052728(01)002377.PMID11803022.
27.PainterHJ,MorriseyJM,MatherMW,VaidyaAB(2007)."Specificroleofmitochondrialelectrontransportinblood
stagePlasmodiumfalciparum".Nature446(7131):8891.Bibcode:2007Natur.446...88P.doi:10.1038/nature05572.
PMID17330044.
28.RamsayRR,SteenkampDJ,HusainM(1987)."Reactionsofelectrontransferflavoproteinandelectrontransfer
flavoprotein:ubiquinoneoxidoreductase".Biochem.J.241(3):88392.doi:10.1042/bj2410883.PMC1147643.
PMID3593226.
29.ZhangJ,FrermanFE,KimJJ(2006)."Structureofelectrontransferflavoproteinubiquinoneoxidoreductaseandelectron
transfertothemitochondrialubiquinonepool".Proc.Natl.Acad.Sci.U.S.A.103(44):162127.
Bibcode:2006PNAS..10316212Z.doi:10.1073/pnas.0604567103.PMC1637562.PMID17050691.
30.IkedaY,DabrowskiC,TanakaK(25January1983)."SeparationandpropertiesoffivedistinctacylCoA
dehydrogenasesfromratlivermitochondria.Identificationofanew2methylbranchedchainacylCoAdehydrogenase".
J.Biol.Chem.258(2):106676.PMID6401712.
31.RuzickaFJ,BeinertH(1977)."Anewironsulfurflavoproteinoftherespiratorychain.Acomponentofthefattyacid
betaoxidationpathway"(PDF).J.Biol.Chem.252(23):84405.PMID925004.
32.IshizakiK,LarsonTR,SchauerN,FernieAR,GrahamIA,LeaverCJ(2005)."ThecriticalroleofArabidopsiselectron
transferflavoprotein:ubiquinoneoxidoreductaseduringdarkinducedstarvation".PlantCell17(9):2587600.
doi:10.1105/tpc.105.035162.PMC1197437.PMID16055629.
33.BerryEA,GuergovaKurasM,HuangLS,CroftsAR(2000)."Structureandfunctionofcytochromebccomplexes".
Annu.Rev.Biochem.69:100575.doi:10.1146/annurev.biochem.69.1.1005.PMID10966481.
34.CroftsAR(2004)."Thecytochromebc1complex:functioninthecontextofstructure".Annu.Rev.Physiol.66:689733.
doi:10.1146/annurev.physiol.66.032102.150251.PMID14977419.
35.IwataS,LeeJW,OkadaK,LeeJK,IwataM,RasmussenB,LinkTA,RamaswamyS,JapBK(1998)."Complete
13/18
6/17/2016
35.IwataS,LeeJW,OkadaK,LeeJK,IwataM,RasmussenB,LinkTA,RamaswamyS,JapBK(1998)."Complete
structureofthe11subunitbovinemitochondrialcytochromebc1complex".Science281(5373):6471.
Bibcode:1998Sci...281...64I.doi:10.1126/science.281.5373.64.PMID9651245.
36.TrumpowerBL(1990)."TheprotonmotiveQcycle.Energytransductionbycouplingofprotontranslocationtoelectron
transferbythecytochromebc1complex"(PDF).J.Biol.Chem.265(20):1140912.PMID2164001.
37.HunteC,PalsdottirH,TrumpowerBL(2003)."Protonmotivepathwaysandmechanismsinthecytochromebc1
complex".FEBSLett.545(1):3946.doi:10.1016/S00145793(03)003910.PMID12788490.
38.CalhounMW,ThomasJW,GennisRB(1994)."Thecytochromeoxidasesuperfamilyofredoxdrivenprotonpumps".
TrendsBiochem.Sci.19(8):32530.doi:10.1016/09680004(94)90071X.PMID7940677.
39.TsukiharaT,AoyamaH,YamashitaE,TomizakiT,YamaguchiH,ShinzawaItohK,NakashimaR,YaonoR,
YoshikawaS(1996)."Thewholestructureofthe13subunitoxidizedcytochromecoxidaseat2.8A".Science272
(5265):113644.Bibcode:1996Sci...272.1136T.doi:10.1126/science.272.5265.1136.PMID8638158.
40.YoshikawaS,MuramotoK,ShinzawaItohK,AoyamaH,TsukiharaT,ShimokataK,KatayamaY,ShimadaH(2006).
"Protonpumpingmechanismofbovineheartcytochromecoxidase".Biochim.Biophys.Acta1757(910):11106.
doi:10.1016/j.bbabio.2006.06.004.PMID16904626.
41.RasmussonAG,SooleKL,ElthonTE(2004)."AlternativeNAD(P)Hdehydrogenasesofplantmitochondria".AnnuRev
PlantBiol55:2339.doi:10.1146/annurev.arplant.55.031903.141720.PMID15725055.
42.MenzRI,DayDA(1996)."Purificationandcharacterizationofa43kDarotenoneinsensitiveNADHdehydrogenase
fromplantmitochondria".J.Biol.Chem.271(38):2311720.doi:10.1074/jbc.271.38.23117.PMID8798503.
43.McDonaldA,VanlerbergheG(2004)."BranchedmitochondrialelectrontransportintheAnimalia:presenceofalternative
oxidaseinseveralanimalphyla".IUBMBLife56(6):33341.doi:10.1080/15216540400000876.PMID15370881.
44.SluseFE,JarmuszkiewiczW(1998)."Alternativeoxidaseinthebranchedmitochondrialrespiratorynetwork:an
overviewonstructure,function,regulation,androle".Braz.J.Med.Biol.Res.31(6):73347.doi:10.1590/S0100
879X1998000600003.PMID9698817.
45.MooreAL,SiedowJN(1991)."Theregulationandnatureofthecyanideresistantalternativeoxidaseofplant
mitochondria".Biochim.Biophys.Acta1059(2):12140.doi:10.1016/S00052728(05)801975.PMID1883834.
46.VanlerbergheGC,McIntoshL(1997)."ALTERNATIVEOXIDASE:FromGenetoFunction".Annu.Rev.Plant
Physiol.PlantMol.Biol.48:703734.doi:10.1146/annurev.arplant.48.1.703.PMID15012279.
47.ItoY,SaishoD,NakazonoM,TsutsumiN,HiraiA(1997)."Transcriptlevelsoftandemarrangedalternativeoxidase
genesinriceareincreasedbylowtemperature".Gene203(2):1219.doi:10.1016/S03781119(97)005027.
PMID9426242.
48.MaxwellDP,WangY,McIntoshL(1999)."Thealternativeoxidaselowersmitochondrialreactiveoxygenproductionin
plantcells".Proc.Natl.Acad.Sci.U.S.A.96(14):82716.Bibcode:1999PNAS...96.8271M.
doi:10.1073/pnas.96.14.8271.PMC22224.PMID10393984.
49.LenazG(2001)."AcriticalappraisalofthemitochondrialcoenzymeQpool".FEBSLett.509(2):1515.
doi:10.1016/S00145793(01)031726.PMID11741580.
50.HeinemeyerJ,BraunHP,BoekemaEJ,KourilR(2007)."AstructuralmodelofthecytochromeCreductase/oxidase
supercomplexfromyeastmitochondria".J.Biol.Chem.282(16):122408.doi:10.1074/jbc.M610545200.
PMID17322303.
51.SchggerH,PfeifferK(2000)."Supercomplexesintherespiratorychainsofyeastandmammalianmitochondria".EMBO
J.19(8):177783.doi:10.1093/emboj/19.8.1777.PMC302020.PMID10775262.
52.SchggerH(2002)."Respiratorychainsupercomplexesofmitochondriaandbacteria".Biochim.Biophys.Acta1555(1
3):1549.doi:10.1016/S00052728(02)002712.PMID12206908.
53.SchggerH,PfeifferK(2001)."TheratioofoxidativephosphorylationcomplexesIVinbovineheartmitochondriaand
thecompositionofrespiratorychainsupercomplexes".J.Biol.Chem.276(41):378617.doi:10.1074/jbc.M106474200.
PMID11483615.
54.GupteS,WuES,HoechliL,HoechliM,JacobsonK,SowersAE,HackenbrockCR(1984)."Relationshipbetween
lateraldiffusion,collisionfrequency,andelectrontransferofmitochondrialinnermembraneoxidationreduction
components".Proc.Natl.Acad.Sci.U.S.A.81(9):260610.Bibcode:1984PNAS...81.2606G.
doi:10.1073/pnas.81.9.2606.PMC345118.PMID6326133.
55.NealsonKH(1999)."PostVikingmicrobiology:newapproaches,newdata,newinsights".OrigLifeEvolBiosph29(1):
7393.doi:10.1023/A:1006515817767.PMID11536899.
56.SchferG,EngelhardM,MllerV(1999)."BioenergeticsoftheArchaea".Microbiol.Mol.Biol.Rev.63(3):570620.
PMC103747.PMID10477309.
57.IngledewWJ,PooleRK(1984)."TherespiratorychainsofEscherichiacoli".Microbiol.Rev.48(3):22271.
PMC373010.PMID6387427.
58.UndenG,BongaertsJ(1997)."AlternativerespiratorypathwaysofEscherichiacoli:energeticsandtranscriptional
regulationinresponsetoelectronacceptors".Biochim.Biophys.Acta1320(3):21734.doi:10.1016/S0005
14/18
6/17/2016
regulationinresponsetoelectronacceptors".Biochim.Biophys.Acta1320(3):21734.doi:10.1016/S0005
2728(97)000340.PMID9230919.
59.CecchiniG,SchrderI,GunsalusRP,MaklashinaE(2002)."Succinatedehydrogenaseandfumaratereductasefrom
Escherichiacoli".Biochim.Biophys.Acta1553(12):14057.doi:10.1016/S00052728(01)002389.PMID11803023.
60.FreitagA,BockEBock(1990)."EnergyconservationinNitrobacter".FEMSMicrobiologyLetters66(13):15762.
doi:10.1111/j.15746968.1990.tb03989.x.
61.StarkenburgSR,ChainPS,SayavedraSotoLA,HauserL,LandML,LarimerFW,MalfattiSA,KlotzMG,Bottomley
PJ,ArpDJ,HickeyWJ(2006)."GenomesequenceofthechemolithoautotrophicnitriteoxidizingbacteriumNitrobacter
winogradskyiNb255".Appl.Environ.Microbiol.72(3):205063.doi:10.1128/AEM.72.3.20502063.2006.
PMC1393235.PMID16517654.
62.YamanakaT,FukumoriY(1988)."ThenitriteoxidizingsystemofNitrobacterwinogradskyi".FEMSMicrobiol.Rev.4
(4):25970.doi:10.1111/j.15746968.1988.tb02746.x.PMID2856189.
63.IuchiS,LinEC(1993)."AdaptationofEscherichiacolitoredoxenvironmentsbygeneexpression".Mol.Microbiol.9
(1):915.doi:10.1111/j.13652958.1993.tb01664.x.PMID8412675.
64.CalhounMW,OdenKL,GennisRB,deMattosMJ,NeijsselOM(1993)."EnergeticefficiencyofEscherichiacoli:
effectsofmutationsincomponentsoftheaerobicrespiratorychain"(PDF).J.Bacteriol.175(10):30205.PMC204621.
PMID8491720.
65.BoyerPD(1997)."TheATPsynthaseasplendidmolecularmachine".Annu.Rev.Biochem.66:71749.
doi:10.1146/annurev.biochem.66.1.717.PMID9242922.
66.VanWalravenHS,StrotmannH,SchwarzO,RumbergB(1996)."TheH+/ATPcouplingratiooftheATPsynthasefrom
thiolmodulatedchloroplastsandtwocyanobacterialstrainsisfour".FEBSLett.379(3):30913.doi:10.1016/0014
5793(95)015361.PMID8603713.
67.YoshidaM,MuneyukiE,HisaboriT(2001)."ATPsynthaseamarvellousrotaryengineofthecell".Nat.Rev.Mol.Cell
Biol.2(9):66977.doi:10.1038/35089509.PMID11533724.
68.SchemidtRA,QuJ,WilliamsJR,BrusilowWS(1998)."EffectsofcarbonsourceonexpressionofF0genesandonthe
stoichiometryofthecsubunitintheF1F0ATPaseofEscherichiacoli".J.Bacteriol.180(12):32058.PMC107823.
PMID9620972.
69.NelsonN,PerzovN,CohenA,HagaiK,PadlerV,NelsonH(1January2000)."Thecellularbiologyofprotonmotive
forcegenerationbyVATPases".J.Exp.Biol.203(Pt1):8995.PMID10600677.
70.RubinsteinJL,WalkerJE,HendersonR(2003)."StructureofthemitochondrialATPsynthasebyelectron
cryomicroscopy".EMBOJ.22(23):618292.doi:10.1093/emboj/cdg608.PMC291849.PMID14633978.
71.LeslieAG,WalkerJE(2000)."StructuralmodelofF1ATPaseandtheimplicationsforrotarycatalysis".Philos.Trans.
R.Soc.Lond.,B,Biol.Sci.355(1396):46571.doi:10.1098/rstb.2000.0588.PMC1692760.PMID10836500.
72.NojiH,YoshidaM(2001)."Therotarymachineinthecell,ATPsynthase".J.Biol.Chem.276(3):16658.
doi:10.1074/jbc.R000021200.PMID11080505.
73.CapaldiRA,AggelerR(2002)."MechanismoftheF(1)F(0)typeATPsynthase,abiologicalrotarymotor".Trends
Biochem.Sci.27(3):15460.doi:10.1016/S09680004(01)020515.PMID11893513.
74.DimrothP,vonBallmoosC,MeierT(2006)."CatalyticandmechanicalcyclesinFATPsynthases.FourthintheCycles
ReviewSeries".EMBORep.7(3):27682.doi:10.1038/sj.embor.7400646.PMC1456893.PMID16607397.
75.GresserMJ,MyersJA,BoyerPD(25October1982)."CatalyticsitecooperativityofbeefheartmitochondrialF1
adenosinetriphosphatase.Correlationsofinitialvelocity,boundintermediate,andoxygenexchangemeasurementswith
analternatingthreesitemodel".J.Biol.Chem.257(20):120308.PMID6214554.
76.DimrothP(1994)."Bacterialsodiumioncoupledenergetics".AntonieVanLeeuwenhoek65(4):38195.
doi:10.1007/BF00872221.PMID7832594.
77.BecherB,MllerV(1994)."DeltamuNa+drivesthesynthesisofATPviaandeltamuNa(+)translocatingF1F0ATP
synthaseinmembranevesiclesofthearchaeonMethanosarcinamazeiG1".J.Bacteriol.176(9):254350.
PMC205391.PMID8169202.
78.MllerV(2004)."AnexceptionalvariabilityinthemotorofarchaelA1A0ATPases:frommultimerictomonomeric
rotorscomprising613ionbindingsites".J.Bioenerg.Biomembr.36(1):11525.
doi:10.1023/B:JOBB.0000019603.68282.04.PMID15168615.
79.DaviesKJ(1995)."Oxidativestress:theparadoxofaerobiclife".Biochem.Soc.Symp.61:131.
doi:10.1042/bss0610001.PMID8660387.
80.RattanSI(2006)."Theoriesofbiologicalaging:genes,proteins,andfreeradicals".FreeRadic.Res.40(12):12308.
doi:10.1080/10715760600911303.PMID17090411.
81.ValkoM,LeibfritzD,MoncolJ,CroninMT,MazurM,TelserJ(2007)."Freeradicalsandantioxidantsinnormal
physiologicalfunctionsandhumandisease".Int.J.Biochem.CellBiol.39(1):4484.doi:10.1016/j.biocel.2006.07.001.
PMID16978905.
82.RahaS,RobinsonBH(2000)."Mitochondria,oxygenfreeradicals,diseaseandageing".TrendsBiochem.Sci.25(10):
5028.doi:10.1016/S09680004(00)016741.PMID11050436.
15/18
6/17/2016
5028.doi:10.1016/S09680004(00)016741.PMID11050436.
83.FinkelT,HolbrookNJ(2000)."Oxidants,oxidativestressandthebiologyofageing".Nature408(6809):23947.
doi:10.1038/35041687.PMID11089981.
84.KadenbachB,RamzanR,WenL,VogtS(March2010)."NewextensionoftheMitchellTheoryforoxidative
phosphorylationinmitochondriaoflivingorganisms".Biochim.Biophys.Acta1800(3):20512.
doi:10.1016/j.bbagen.2009.04.019.PMID19409964.
85.EchtayKS,RousselD,StPierreJ,JekabsonsMB,CadenasS,StuartJA,HarperJA,RoebuckSJ,MorrisonA,
PickeringS,ClaphamJC,BrandMD(January2002)."Superoxideactivatesmitochondrialuncouplingproteins".Nature
415(6867):969.Bibcode:2002Natur.415...96E.doi:10.1038/415096a.PMID11780125.
86.JoshiS,HuangYG(1991)."ATPsynthasecomplexfrombovineheartmitochondria:theoligomycinsensitivity
conferringproteinisessentialfordicyclohexylcarbodiimidesensitiveATPase".Biochim.Biophys.Acta1067(2):2558.
doi:10.1016/00052736(91)900519.PMID1831660.
87.TsubakiM(1993)."FouriertransforminfraredstudyofcyanidebindingtotheFea3CuBbinuclearsiteofbovineheart
cytochromecoxidase:implicationoftheredoxlinkedconformationalchangeatthebinuclearsite".Biochemistry32(1):
16473.doi:10.1021/bi00052a022.PMID8380331.
88.HeytlerPG(1979)."Uncouplersofoxidativephosphorylation".Meth.Enzymol.MethodsinEnzymology55:46242.
doi:10.1016/00766879(79)550605.ISBN9780121819552.PMID156853.
89.LambertAJ,BrandMD(2004)."Inhibitorsofthequinonebindingsiteallowrapidsuperoxideproductionfrom
mitochondrialNADH:ubiquinoneoxidoreductase(complexI)".J.Biol.Chem.279(38):3941420.
doi:10.1074/jbc.M406576200.PMID15262965.
90.DervartanianDV,VeegerC(November1964)."STUDIESONSUCCINATEDEHYDROGENASE.I.SPECTRAL
PROPERTIESOFTHEPURIFIEDENZYMEANDFORMATIONOFENZYMECOMPETITIVEINHIBITOR
COMPLEXES".Biochim.Biophys.Acta92(2):23347.doi:10.1016/09266569(64)901828.PMID14249115.
91.RicquierD,BouillaudF(2000)."Theuncouplingproteinhomologues:UCP1,UCP2,UCP3,StUCPandAtUCP".
Biochem.J.345(2):16179.doi:10.1042/02646021:3450161.PMC1220743.PMID10620491.
92.BoreckJ,VercesiAE(2005)."Plantuncouplingmitochondrialproteinandalternativeoxidase:energymetabolismand
stress".Biosci.Rep.25(34):27186.doi:10.1007/s1054000528892.PMID16283557.
93.HardenA,YoungWJ.Young(1906)."Thealcoholicfermentofyeastjuice".ProceedingsoftheRoyalSocietyB(77):
40520.doi:10.1098/rspb.1906.0029.
94.KalckarHM(1974)."Originsoftheconceptoxidativephosphorylation".Mol.Cell.Biochem.5(12):5563.
doi:10.1007/BF01874172.PMID4279328.
95.LipmannF(1941)."Metabolicgenerationandutilizationofphosphatebondenergy".AdvEnzymol1:99162.
doi:10.4159/harvard.9780674366701.c141.
96.FriedkinM,LehningerAL(1April1949)."Esterificationofinorganicphosphatecoupledtoelectrontransportbetween
dihydrodiphosphopyridinenucleotideandoxygen".J.Biol.Chem.178(2):61144.PMID18116985.
97.H.M.Kalckar(1991)."50yearsofbiologicalresearchfromoxidativephosphorylationtoenergyrequiringtransport
regulation".AnnualReviewofBiochemistry60:137.doi:10.1146/annurev.bi.60.070191.000245.PMID1883194.
98.Belitser,V.A.,Tsibakova,E.T.(1939)."Aboutphosphorilationmechanismcoupledwithrespiration".Biokhimya4:
516534.
99.SlaterEC(1953)."Mechanismofphosphorylationintherespiratorychain".Nature172(4387):9758.
Bibcode:1953Natur.172..975S.doi:10.1038/172975a0.PMID13111237.
100.MitchellP(1961)."Couplingofphosphorylationtoelectronandhydrogentransferbyachemiosmotictypeof
mechanism".Nature191(4784):1448.Bibcode:1961Natur.191..144M.doi:10.1038/191144a0.PMID13771349.
101.MiltonH.SaierJr."PeterMitchellandtheVitalForce".Retrieved20140525.
102.Mitchell,Peter(1978)."DavidKeilin'sRespiratoryChainConceptandItsChemiosmoticConsequences"(Pdf).Nobel
lecture.NobelFoundation.Retrieved20070721.
103.PullmanME,PenefskyHS,DattaA,RackerE(1November1960)."Partialresolutionoftheenzymescatalyzing
oxidativephosphorylation.I.Purificationandpropertiesofsolubledinitrophenolstimulatedadenosinetriphosphatase".J.
Biol.Chem.235(11):33229.PMID13738472.
104.BoyerPD,CrossRL,MomsenW(1973)."Anewconceptforenergycouplinginoxidativephosphorylationbasedona
molecularexplanationoftheoxygenexchangereactions".Proc.Natl.Acad.Sci.U.S.A.70(10):28379.
Bibcode:1973PNAS...70.2837B.doi:10.1073/pnas.70.10.2837.PMC427120.PMID4517936.
105."TheNobelPrizeinChemistry1997".NobelFoundation.Retrieved20070721.
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6/17/2016
Furtherreading
Introductory
NelsonDLCoxMM(2004).LehningerPrinciplesofBiochemistry(4thed.).W.H.Freeman.ISBN07167
43396.
SchneiderEDSaganD(2006).IntotheCool:EnergyFlow,ThermodynamicsandLife(1sted.).University
ofChicagoPress.ISBN0226739376.
LaneN(2006).Power,Sex,Suicide:MitochondriaandtheMeaningofLife(1sted.).OxfordUniversity
Press,USA.ISBN0199205647.
Advanced
NichollsDGFergusonSJ(2002).Bioenergetics3(1sted.).AcademicPress.ISBN0125181213.
HaynieD(2001).BiologicalThermodynamics(1sted.).CambridgeUniversityPress.ISBN0521795494.
RajanSS(2003).IntroductiontoBioenergetics(1sted.).Anmol.ISBN8126113642.
WikstromM(Ed)(2005).BiophysicalandStructuralAspectsofBioenergetics(1sted.).RoyalSocietyof
Chemistry.ISBN0854043462.
Externallinks
Generalresources
Animateddiagramsillustratingoxidativephosphorylation(http://www.wiley.com/legacy/college/boyer/0470
003790/animations/electron_transport/electron_transport.htm)WileyandCoConceptsinBiochemistry
Onlinebiophysicslectures(http://www.life.uiuc.edu/crofts/bioph354/)AntonyCrofts,UniversityofIllinois
atUrbanaChampaign
ATPSynthase(http://www.youtube.com/watch?v=PjdPTY1wHdQ)GrahamJohnson
Structuralresources
PDBmoleculeofthemonth:
ATPsynthase(http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pd
b72_1.html)
Cytochromec(http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_month/pd
b36_1.html)
Cytochromecoxidase(http://www.rcsb.org/pdb/static.do?p=education_discussion/molecule_of_the_
month/pdb5_1.html)
InteractivemolecularmodelsatUniversidadeFernandoPessoa:
NADHdehydrogenase(http://www2.ufp.pt/~pedros/anim/2frameien.htm)
succinatedehydrogenase(http://www2.ufp.pt/~pedros/anim/2frameiien.htm)
CoenzymeQcytochromecreductase(http://www2.ufp.pt/~pedros/anim/2frameiiien.htm)
cytochromecoxidase(http://www2.ufp.pt/~pedros/anim/2frameiven.htm)
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