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Physiology Unit1 CELLULARMETABOLISMOFGLUCOSE: KREB’SCYCLEANDETC InPhysiologyToday Glycolysis FateofPyruvate Aerobic- Anaerobic WhatHappens WhentheCellRuns Outof O2? LacticAcidCycle LacticAcidPathwayinHumans • Sometissuesbetteradapttoanaerobicconditions – RBCsdonotcontainmitochondriaandonly usethelactic acidpathway • Whenratioofoxygensupplytooxygenneedfalls belowcriticallevel • Oxygendebt:Theamountofenergyrequiredtoreturn bloodglucoselevelsbacktonormalandtoreplace glycogenreservesinmuscleandliver – Skeletalmuscle • Normaldailyoccurrence • Doesnotharmmuscletissue – CardiacMuscle Ischemia: restrictionof bloodsupply • Cardiacmusclenormallyrespiresaerobically • Myocardialischemiaoccursunderanaerobicconditions CoriCycle LacticAcidtoGlucoseintheLiver AnaerobicMetabolismSummary • Finale- acceptorinanaerobicmetabolismis pyruvicacid • Lacticacidproductioninanimalmuscleoccurs duringoxygendebt • LacticacidneedstobeproducedsothatNAD+ canberegeneratedtokeepglycolysisgoing NetATPproduced=2ATP IntermediateStep ToKrebsCycle Kreb’sCycle • Two turnsoftheKrebscyclearerequiredfor eachmoleofglucose • Attheendofthetwoturns,all oftheoriginal glucosemoleculehasbeenoxidizedto CO2 +H2O • Energyproducedwhenbondsarebrokenis transferredto – 1ATP – 3NADH+H+ – 1FADH2 Kreb’sCycle ElectronTransportSystem • Cristae containmoleculesthatmakeupthe electrontransportsystemutilizedinaerobic respiration • Electrontransportsystemconsistsof4complexes thatreceivesapairofelectronsthentransfersthe electronstothenextcomplex – Cytochrome complex3and4aremembranebound proteinsthatcontainaheme group – Ironreduced,thenoxidizedaselectronsaretransferred – Fe+2toFe+3 ElectronTransportSystem OxidativePhosphorylation FMN: (flavin mononucleotide) coenzyme Q: (ubiquinon) OxidativePhosphorylation • Electronarebeingshuttledfromglycolysisandthe Kreb’scyclebyNADH+H+ andFADH2 • NADH+H+ donateselectronstoFMN – Theresultisthegenerationof3ATPforeachpairofelectrons • FADH2donateselectronstoCoQ – Theresultisthegenerationof2ATPforeachpairofelectrons • Cytochromea3 transferselectronstomolecularoxygen toproducemetabolicH20 – Cytochromea3 isoxidized – Oxygengetsreduced Oxidized NAD+and FAD regenerated TheFinalElectronAcceptor:Oxygen • Oxygenfunctionsasthe finalelectronacceptor – Oxidizescytochromea3 • Oxygenaccepts2 electrons • O2 +4H+--->2H20 Chemiosmosis • InnermitochondrialmembraneallowstransportofH+ throughrespiratoryassemblies – Respiratoryassembliescontainachannelthatpermitsthe passageofH+ – Groupedinto3protonpumps – PumpsH+ frommatrixintotheintermembranespace – CreatesaconcentrationgradientofH+ • Phosphorylationiscoupledtooxidation – H+ passesthroughATPSynthasewhichisaH+ channel – FreeenergyreleasedisusedtomakeATP – Oxidativephosphorylation • ADPandPi ----> ATP GlucoseOxidation Step ATP Produced e- carrier reduced ATP produced Glycolysis 2ATP 2NADH+H+ 6ATP 2NADH+H+ 6ATP 6NADH+H+ 2FADH2 18ATP 4ATP Substrate-level phosphoylation Intermediate Step Kreb’s Cycle 2ATP TOTAL 4ATP Oxidative phosphoylation 34ATP