Chapter 19Oxidative Phosphorylation andPhotophosphorylationPart I) Electron TransportFrom Garrett & GrishamElectrons transferred via NADPHElectrons transferred via NADPHIntermembranespaceOuter Membrane• Contains porin• Allows free diffusion of molecules with molecular weight less than 10,000Inner Membrane• Impermeable to molecules & ions{80% proteins}{30-40% lipids & 60-70% proteins}Provide inner membrane with large surface areaPorins are transmembranechannels for small moleculesMatrix• contains all of TCA cycle enzymes {except, succinatedehydrogenase which is located in the inner membrane}• contains circular DNA, ribosomes and enzymes required to synthesize proteins encoded within the mitochondrial genomeFrom LehningerPrinciples of BiochemistrySeparation of functional complexes of the respiratory chainComponents of the electron transport chain can be purified from the mitochondrial inner membraneFrom LehningerPrinciples of BiochemistryElectron TransportLink between glycolysis, TCA cycle, fatty acid oxidation and electron transport chainDirect link between TCA cycle and electron transport chain•e-carried by reduced coenzymes are passed through a chain of proteins and coenzymes to drive the generation of a proton gradient across the inner mitochondrial membrane2 other ways to feed electrons into ubiquinoneFrom LehningerPrinciples of BiochemistryElectron transfer from NADH to O2involves multi-subunit inner membrane complexes I, III, & IV, plus coenzyme Q and cytochrome c. Within each complex, electrons pass sequentially through a series of electron carriers.NADHFMNFe.SQCyt bFe.SCyt c1Cyt cCyt aCyt a3FADH2Fe.SO2Free Energy Relative to O2 (kcal / mol)The electron transport chainNADH (reductant) + H++ ½ O2 (oxidant) NAD++ H2OElectrons generally fall in energy through the chain - from complexes I and II to complex IVRedox reactions are among a cell's most important enzyme-catalyzed reactions. Oxidation and reduction refer to the transfer of one or more electrons from a donor to an acceptor, generally of another chemical species.The donor is oxidized, the acceptor reduced.Oxidative PhosphorylationThe proton gradient runs downhill to drive the synthesis of ATPElectron Carriers:NAD+/NADH and FAD/FADH2 were introduced earlier 9 FMN (Flavin Mono Nucleotide) is a prosthetic group of some flavoproteins{It is similar in structure to FAD, but lacks the adenine nucleotide}9 In solution FMN (like FAD) can accept 2 e-+ 2 H+to yield FMNH29 When bound at the active site of some enzymes, FMN can accept 1 e-, converting it to the half-reduced semiquinone radical. The semiquinone can accept a second e-to yield FMNH2Prosthetic groups of cytochromesThe heme iron atom can undergo a 1 electron transition between ferric and ferrous states:Fe3++ e-<--> Fe2+ Heme is a prosthetic group of cytochromes Mitochondria has 3 classes of cytochromes, designated a, b, and cFound in HbFrom LehningerPrinciples of BiochemistryStructure of mitochondrial cytochrome cHeme is covalently linked to the protein via S atomsFrom Garrett & Grisham- electron transfer proteins may contain multiple iron-sulfur centers. - transfer only one electron even if they contain two or more iron atoms, because of the close proximity of the iron atoms.a 4-Fe center might cycle between the redox states: Fe3+3, Fe2+1(oxidized) + 1 e-<-->Fe3+2, Fe2+2( reduced)Iron-sulfur centers (Fe-S)Iron-sulfur centersFrom LehningerPrinciples of BiochemistryFerredoxin of the cyanobacterium Anabaena 71202Fe-2S center SFeFrom LehningerPrinciples of BiochemistryProtein bound copper, a one-electron transfer site, which converts between Cu+and Cu2+Ubiquinone (Q or coenzyme Q)From LehningerPrinciples of BiochemistryMobile electron carrierHydrophobic tail allows it to diffuse freely in the hydrophobic core of the inner mitochiondrialmembraneA lipid soluble coenzyme (UQ) shuttle between protein complexesComplex INADH dehydrogenase akaNADH-Coenzyme Q reductaseNADH 2e-donorFMN 1 or 2 e-donorFe-S clusters 1 e-donoro¾ Estimated mass of this complex 850 kD¾ Involves more than 30 polypeptide chains¾ One molecule of FMN¾ As many as 7 Fe-S clusters (2Fe-2S & 4Fe-4S)¾ Precise mechanism of this complex is unknownFrom LehningerPrinciples of BiochemistryComplex IroororoInhibitors of complex I◊ Rotenone is a common insecticide that inhibits complex I◊ Rotenone is obtained from the roots of several species of plants◊ Rats exposed to rotenone over a period of weeks develop symptoms of Parkinson’s disease◊ Appear to inhibits reduction of Q and the oxidation of Fe-S clusters of complex I {Painkiller Demerol also exert inhibitory actions on this complex}Inhibitors of Complex IComplex II¾ Mass of 100 – 140 kD¾ Composed of 4 subunits, including 2 Fe-S proteins ¾ Three types of Fe-S cluster: 4Fe-4S, 3Fe-4S, 2Fe-2S Path: Succinate FADH22Fe2+UQH2Succinate-CoQ Reductaseaka Succinate dehydrogenase(from TCA cycle!)Complex IISuccinate FumarateFADFADH2SuccinatedehydrogenaseH+transport does not occur in this complexorororInhibitors of complex II2-Thenoyltrifluoroacetone & carboxin block complex IIInhibitors of complex IIElectron TransportFrom LehningerPrinciples of
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