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1 Chapter8.Energyandenergytransformations Thechapter8outlineconsistsofthematerialthatwetalkedaboutduringthelecturesand thematerialthatwasleftout.Thematerialthatwasleftoutispresentedheresoyouhad thoroughcomprehensionofthematerialthatwedidtalkabout.Thematerialthatwasleft outwillnotbeexplicitlytested.Therewego. - Energyisabilityofthesystemtodowork.Theunitforenergyisthesameasthe unitofwork–thejoule(J),oracalorie(Cal). - Potentialandkineticenergy - Conceptofaclosedandanopensystem: o Athermodynamicallyclosedsystemisonethatcanexchangeheatandwork withitssurroundings,butnotmatter. o Athermodynamicallyopensystemcanexchangebothenergyandmatter. o Spaceshipisaclosesystem o Organismsareopensystems o Livingcellsareopensystems - Twolawsofthermodynamics o Energyofuniverseisaconstant=aprincipleofconservationofenergy; energycanbetransformedortransferredbutitcannotbecreatedor destroyed. o Energytransformationsareimperfect,someenergyisalwayslostduring transformations; o Thislossofenergyduringtransformationsexhibitsintheincreaseof entropyandenthalpy. o Entropyisanenergystoredinvariousmotionsofatomsandmoleculesin thesystem.ThetermforEntropyisS.TheunitforentropyisJoulesper temperatureinKelvin(J/K). o Enthalpyisheatevolvedorabsorbedduringenergytransformation. o Entropyoftheuniverseincreasesasaresultofenergytransformations.The termforEnthalpyisH.TheunitforEnthalpyisjoule(J). o Spontaneousprocessoccurswithoutanyinputofenergy(howeverlongit takes);thusitisaprocess,orareaction,thatincreasestheentropyofthe universe. o Spontaneousprocessesareexothermicmeaningthattheenergyisreleased inthecourseoftheiroccurrence. o Foranon-spontaneousprocesstooccursomeenergyneedstobe expended. o Non-spontaneousprocessesareendothermicmeaningthattheenergy needstobespentfortheseprocessestooccur. - Gibbsfreeenergyisafunctionthatdescribesastateofasystemandrelatesto itsabilitytodowork. o Gibbsfreeenergyfunctionunitesentropyandenthalpy. o Itisallenergythatisavailabletodowork,thus“freeenergy” equals“availableenergy.” o ThetermforGibbsfreeenergyisG. o TheformulaforGibbsenergyisG=H-T*SwhereTistemperatureinKelvin. 2 - - o Youcanseefromthisformulathatalossoftheenergyintheformofhear meansareductionintheabilityofthesystemtodowork. o TheprocessesinthesystemthataredescribedbytheGibbsfreeenergyare reversible.Thedirectionoftheprocess(forwardorreverse)isdetermined bythechangeintheGibbsfreeenergyofthereaction. o TheGibbsenergyisminimizedwhenasystemreacheschemicalequilibrium atconstantpressureandtemperature. Biologicalsystemsarehighlyorganized;cellscreateorderedstructuresfromthe lessorderedmaterials;energyisspenttodothat. o Complexlivingsystemsincreasetheirownorderbydecreasingentropyof thesurrounding/universe. o Inclosedsystems,reactionseventuallyreachequilibrium,noworkwhenis possible,thusadeathwilloccur. o Cellsareopensystemsthatarenotinequilibrium,buttheyareexperiencing aconstantflowofmaterialsinandout. o Adefiningfeatureoflifeisthatcellsconstantlyconductmetabolismthatis neverinequilibrium. o Metabolismcanbedefinedasaperpetualdisequilibrium. AmetabolicreactionrepresentsasystemthatcanbedescribedintermsofGibbs freeenergy.Changesintheenergyofasystemaredescribedintermsofchanges inGibbsenergy.ThechangeinGibbsenergyofthesystemcanbepositiveor negative.Forachemicalreaction,includingmetabolicreactions,thesignofthe changeinGibbsfreeenergydetermineswhetherareactionisspontaneousornonspontaneous. o ChangesinGibbsfreeenergyofthesystemaredescribedintermsof correspondingchangesinentropyandenthalpy. o AtermforachangeinGibbsfreeenergyisΔG.TheunitofΔGisCal/Mol o AtermforchangeinenthalpyisΔS. o AtermforchangeinentropyisΔH. o AformulaforachangeinGibbsfreeenergyis ΔG=ΔH-T*ΔS o ThechangeoftheGibbsfreeenergyofthereactionisanultimate determinantofthedirectionofthereaction. o IfΔGforreactioniszero,thesystemisinequilibrium. o IfΔGforreactionisnegative,thereactionwillgoforwardspontaneously. Suchreactionissaidtobeexergonic. o IfΔGforreactionispositive,thereactionwillgobackwards.Forsuch reactiontogoforwardsomeenergywillneedtobespent.Thereactionfor whichΔGispositiveissaidtobeendergonic. o AnexergonicreactionevenifithasverynegativeΔGstillrequiresan activationenergytobespentforthereactiontogetstarted. o Inlivingcells,activationenergyisprovidedbytheenzymes. o Anendergonicreactionrequiresnotonlytheactivationenergytobespent, butalsotheadditionalenergyexpendituretoenablecreatingproduct chemicalspeciespossessingtheGibbsfreeenergythatishigherthanthatof theoriginalreactants. 3 o Thus,todeterminethecourseofreaction,oneneedstobeabletocalculatea changeinGibbsfreeenergy. o Cellsperformbothexergonicandendergonicreactionsusingenzymes.You canseefromtwodiagramsabovethatenergyrequiredtopowerendergonic reactionismuchhighercomparedtotheenergythatisrequiredtopoweran exergonicreaction. o Becausethecourseofreactionisalsodeterminedbytheells o OnlytheprocesseswithnegativeΔGarespontaneous. o Spontaneousprocessescanbeharnessedtoperformwork. - Metabolicreactionsinlivingsystemsareperformedbytheenzymes. o Enzymesfunctionascatalyststhatfacilitatetransformationsofreactants intotheproducts. o IfGibbsfreeenergyfortheproductsislowerthanitisforthereactants,then ΔGisnegativeandthereactionisspontaneous.However,itmighttake millionsofyearsfortheproductstoform.Sothecellsuseenzymestospeed upthereactions. o Enzymesspeedupthereactionsbycreatingintermediateproducts,socalled transitionstateintermediates. 4 - o TransitionstateintermediatespossessGibbsfreeenergythatishigherthan thatofthereactants,thereforesomeenergyneedstobespentforthe catalyzedreactiontogoforward. o Enzymescoupleexergonic o Incellsthisadditionalenergyusually,butnotalways,comesinformofATP. o TotalΔGforanenzymaticreactionisasumofΔG0thatisaconstant determinedforthestandardenzymaticconditions(astandardtemperature, pH,pressure,andconcentrationofproductsandreactants),andasecond termthatdependsonanaturallogarithmoftheconcentrationsof productsandreactants.Thatrelationshipimpliesthatcellcanperform highlythermodynamicallyunfavorablereactionsnotonlybyinvestingsome energybutalsobyincreasingtheconcentrationofthereactants. Metabolismincludecatabolismandanabolism. o Aseriesofmetabolicreactionsconstituteametabolicpathway. o Metabolicpathwayscanbecatabolicoranabolic. o Acatabolicpathwayincellreleasesfreeenergyinaseriesofreactions.This energyisharvestedandthenusedtodoworkinacell. o Acatabolicpathwayisexothermic. o Ananabolicpathwayinacelltransformsexistingmoleculesandcreatesnew molecules.Itusesenergyreleasedduringcatabolicreactionstodothis work. o Ananabolicpathwayisendothermic. o Aworkdonebyacellincludes: § MakingmacromoleculessuchasDNAandproteins. § Movingmoleculesaround. § Conductingactionpotentialsinnervoussystem. § Celldivision. § Cellgrowth. § Secretionofproductsmadeincell. o Enzymescouplecatabolicandmetabolicreactionstodowork. Chapter9.Bioenergetics-theenergeticsoflivingsystems. - Theenergeticsoflivingsystemsincludestransformationofoutside-systemenergy (suchassunlight,chemicalreactions,orheat)intotheenergyofchemicalbondsby theautotrophs,followedbytheutilizationofthisenergyofchemicalbondsbythe heterotrophs. o Autotrophsincludephotoautotrophsandchemoautotrophs. o Photoautotrophsaregreenplantsandalgaethatutilizesunlight. o Chemoautotrophsareprokaryotesbacteriaandarchaeathatobtaintheir energybyoxidationofinorganiccompounds. o Heterotrophsobtainenergybyoxidationoforganic(carbon-containing) compoundscreatedbyautotrophs. - Oxidationislossofelectron(s)byachemicalspecies(suchasanatomoranion). Againofelectron(s)byachemicalspeciesiscalledareduction. o Oxidationandreductionreactionsarealwayscoupledtogether.Theyare twosidesofthesamecoin:thereisnooxidationwithoutreduction,andvise versa.ThisiswhythesekindofchemicaltransformationsarecalledRedOx reactions. 5 o Aspeciesthatwasoxidizedservedasanelectrondonor. o Aspeciesthatwasreducedservedasanelectronacceptor. o Theconceptofelectrondonor andelectronacceptordoesnot requireawholeelectrontobe transferred.Rather,itisa differenceinrelative electronegativitythatdefines whetheramemberofapairisa donororanacceptor. o Electronegativityisameasure ofthetendencyofanatomto attractabondingpairof electrons. o Electronegativityispossiblebecausetheelectronpairssharedbetween twoatomsarenotnecessarilysharedequally,forexampleinCl2the sharedelectronpairsissharedequallywhileinNaClthe3selectronis strippedfromtheNaatomandisincorporatedintotheelectronicstructure oftheClatom. o Aspeciesthatwasoxidizedoftencanbeoxidizedfurther. o Aspeciesthatwasreducedoftencanbereducedfurther. o Substancesvaryintheirtendencytobecomeoxidizedorreducedi.e.to donateoracceptelectrons. o Ameasureofatendencyofachemicalspeciestoacquireelectronsand therebybereducedisthereduction(orredox)potentialofasubstance. Theunitofredoxpotentialismillivolts(mV).Oxygenhasveryhighredox potential. o Thehighertheelectronegativitythehighertheredoxpotentialofchemical species. o Manyspeciescanactasbothelectrondonorsorelectronacceptors dependingontheenvironmentandothersubstancestheyreactwith. o Electronsflowfromdonorswithlow(ormorenegative)redoxpotentialto acceptorswithhigh(ormorepositive)redoxpotential. o Becauseonlyareductionhalfofaredoxreactionisconsideredinaredox potentialconcept,onlyaredoxhalfofacompleteredoxreactionistaken intoaccountwhencomparingredoxpotentialofchemicalspecies. o Aredoxhalf-reactionisonewhichshowseitherreductionORoxidation,but notboth. o Considerareaction2Mg(s)+O2(g)→2MgO(s) Sincethereare2Mgonleftside,atotalof4electronsarelostaccordingto thefollowingoxidationhalfreaction: 2Mg(s)→2Mg2++4e− Ontheotherhand,O2wasreduced:itsoxidationstategoesfrom0to-2. Thus,areductionhalf-reactioncanbewrittenfortheO2asitgains4 electrons: O2(g)+4e−→2O2− Theoverallreactionisthesumofbothhalf-reactions: 2Mg(s)+O2(g)+4e−→2Mg2++2O2−+4e− 6 However,onlythereductionhalfreactionO2(g)+4e−→2O2− isconsideredwhencomparingoxygenredoxpotentialwiththatofanother chemicalspecies.Thehalf-reactionapproachallowstorankchemical speciesbytheirredoxpotential.Youcanseeinthetablebelowthatoxygen isoxidizedinthereactionthatleadstothereductionofCrO2toCrmetal. o Chemoautotrophsuseelectroncarrierstotransferelectronsfroma reductanttoanacceptorwithamorepositive(higher)reductionpotential, andtheytherebyallowthereleaseoffreeenergy,whichisoftenusedinthe formationofATP. o TheElectrontowerorganizedthereduction potentialsofhalfreactionsinawaythatallows visualizingasequenceofmetabolicreactions leadingtosequentialreleaseoftheenergy storedinthechemicalbondsofglucose. o Considerburningglucoseinoxygen–this processisveryfastandreleasesalotofheat. Inlivingcells,thesameprocessishappening veryslowlyutilizingametabolicpathway calledcellularrespiration. o Theenergeticsoflivingsystemsisbasedona step-wiseoxidation(akindofthestaircasetowalkdownthetower)of organiccompounds,mainlyglucose. o AconceptofElectronTowerhelpstovisualizethatthegreaterthefallof electronsthemorepotentialenergythatcanbeharvestedinthebalanced reaction. 7 Electron donors Electron acceptors -Thereactionformulaforglucosecombustionreactionis C6H12O6+6O2--->6CO2+6H2O+energy-thesameasaforthecellular respirationreaction.Duringthecellularrespiration,thefuel(glucose)isoxidized, andtheoxygenisreduced. o GlucoseoxidationishighlyexergonicreactionwithΔG-686Kcal/Mol. o Whyitisthatbeingsuchanexergonicreaction,glucosecombustiondoes happenspontaneouslyinthepresenceofoxygen? o Asmentionedabove,theactivationenergyisneeded. - Whyitisthatthelivingcellsarecapableofreleasingenergyslowlyinmultiple smallsteps? 8 o Becauselivingcellshaveavarietyofelectroncarriers,andeachisusedin particulartypesofredoxreactions;theparticularcarrierusedinanygiven reactionwilldependonthenatureandlocationofthereaction. o Electroncarriersaremoleculesthatarejustbelowtheglucoseinthe electrontowerandincludeNAD+,NADP+,andFAD. o Duringvariousstepsofglucoseoxidation,NAD+,NADP+,andFADare reducedtoNADH,NADPH,andFADH2. o Theenergystoredinelectroncarriersisstoredtobeharnessedlaterinthe formofATPthatservesasanenergycurrencyinlivingcells.ATPpossesses high-energyphosphatebondsthatreleaseenergypertheirhydrolysis. - Cellularrespirationincludesthreesteps: o Glycolysis o Krebscycle o Oxidativephosphorylation 9 - Glycolysisisthefirststepinglucosecatabolism. o Glycolysisisauniversalpathway;itpresentinallorganisms:fromyeastto mammals. o Ineukaryotes,glycolysistakesplaceinthecytosol. o Glycolysisisanaerobic;itdoesnotrequireoxygen. o Netreactionofglycolysisis: Glucose+2NAD++2Pi+2ADP=2pyruvate+2ATP+2NADH+2H2O -ATPIsInitiallyRequired(Investmentstage,ATPisconsumedinsteps1and3): o Reaction1:Phosphorylationofglucosetoglucose-6phosphate. o Thisreactionrequiresenergyandsoitiscoupledtothe hydrolysisofATPtoADPandPi. o Enzymehexokinasephosphorylatestheglucoseandthusglucosebecomes highlycharged.Chargedglucoseisunabletocrossthecellmembrane anymore.Thus,onceglucoseentersthecell,itgetsphosphorylated andtrapped. o Thisstepisirreversible.Glucosetransporterstransportonlyfreeglucose, notphosphorylatedglucose. o Reaction2:Isomerizationofglucose-6-phosphatetofructose6-phosphate. o Thisisareversiblereaction.Thefructose-6-phosphateisquickly consumedandtheforwardreactionisfavored. o Reaction3:isanotherkinasereaction.Phosphorylationofthehydroxyl grouponC1formingfructose-1,6-bisphosphate. o Enzyme:phosphofructokinase.Thisallostericenzymeregulatesthepace ofglycolysis. o ReactioniscoupledtothehydrolysisofanATPtoADPandPi. o Thisisthesecondirreversiblereactionoftheglycolyticpathway. o Reaction4:fructose-1,6-bisphosphateissplitinto23-carbonmolecules, DHAPandGAP. o Reaction5:DHAPandGAPareisomersofeachotherandcanreadilyinterconvertbytheactionoftheenzymetriose-phosphateisomerase. o GAPisasubstrateforthenextstepinglycolysissoalloftheDHAPis eventuallydepleted.So,2moleculesofGAPareformedfromeach moleculeofglucose o Uptothisstep,2moleculesofATPwererequiredforeachmoleculeof glucosebeingoxidized - ATPisProducedinthepayoffstageofglycolysis(steps7and10) o Theremainingstepsreleaseenoughenergytoshiftthebalancesheettothe positiveside.Thispartoftheglycolyticpathwayiscalledasthepayoffor harveststage. o Sincethereare2GAPmoleculesgeneratedfromeachglucose,eachofthe remainingreactionsoccurtwiceforeachglucosemoleculebeingoxidized. o Reaction6:GAPisdehydrogenatedbytheenzymeGAPDH.Intheprocess, NAD+isreducedtoNADH+H+fromNAD.TheproductisBPG. o Reaction7:BPGhasahigh-energybondatC1.Thishigh-energybondis hydrolyzedandtheenergyreleasedisusedtogenerateATPfromADP. Product:3-phosphoglycerate. o Reaction8:ThephosphategroupisshiftedfromC3toC2toform2- phosphoglycerate.Enzyme:phosphoglyceratemutase. o Reaction9:Dehydration;awatermoleculeisremovedtoform phosphoenolpyruvate. 10 o Inglycolysis,theATPisproducedbythesubstratelevelphosphorylation thatisaccomplishedbythetransferofaphosphategroupfromasubstrate totheADP.MechanismofATPproductionisdifferentduringtheoxidative phosphorylationwhereitisproducedbytheactionofenzymeATP synthase. o Reaction10:Enolphosphatehasahighenergybond.Itishydrolyzedto formpyruvatewiththesynthesisofATP.Thisirreversiblereactionis catalyzedbytheenzymepyruvatekinase. -Fateofpyruvatedependsontheavailabilityofoxygen. o Duringtheglycolysis,glucoseissplitintotwo3-carbonmoleculesof pyruvate. o NADHisformedfromNAD+duringglycolysis. o Theredoxbalanceofthecellhastobemaintainedforfurthercyclesof glycolysistocontinue. o Therefore,NAD+shouldberegenerated. o NAD+canberegeneratedbyoneofthefollowingreactions/pathways: § Pyruvateisconvertedtolactate § Pyruvateisconvertedtoethanol § InthepresenceofO2,NAD+isregeneratedbyETC.Pyruvateis convertedtoacetylCoAwhichentersTCAcycleandgetscompletely oxidizedtoCO2. - LactateFermentationinmuscles o LactateisformedintheactivemuscletoregenerateNAD+fromNADHso thatglycolysiscancontinue. o Inhighlyactivemuscle,thereisanaerobicglycolysisbecausethesupplyof O2cannotkeepupwiththedemandforATP,lactatebuildsupcausinga dropinpHwhichinactivatesglycolyticenzymes;thesymptomsbeingpain andfatigueofthemuscle. o ThemusclecannotspareNAD+forre-conversionoflactatebackto pyruvate. o Lactateistransportedtotheliverwhereitcanbereconvertedtopyruvate bythereversereactionandpyruvatethenconvertedtoglucosethroughthe gluconeogenesis. o Theglucoseissuppliedbythelivertovarioustissuesincludingmuscle. o Thisinter-organcooperationduringhighmuscularactivityiscalledasthe Coricycle. -SubstratecycleorFutilecycle o Inasubstratecycle,thereisexpenseofATPwithoutacoupledbiosynthetic reaction,thus,itisalsocalledasafutilecycle o Exampleincludestep2ofglycolysis • F-6-P+ATP(PFK)F-1,6-BP+ADPF-1,6-BP+H2OFBPaseF-6-P+Pi • Net:ATP+H2OADP+Pi+energy(heat) o Thisreactionsisutilizedinbrownfatofmammalstomaintainbody temperature. -Citricacidcycle;AKAKrebscycle;AKATCAcycle. - Ifoxygenisavailable,thenextstep(aftertheglycolysisiscompleted)isthe formationofacetylcoenzymeA(acetylCoA)whichistheinitiatorofthecitricacid cycleandlinkscitricacidcycletotheglycolysis. 11 - - InthepresenceofO2thepyruvateCH3COCOO−istransportedintothe mitochondrionaidedbyaspecialtransportprotein.Pyruvateisacharged moleculeandcannotfreelycrossthemembrane. OneenzymePDHcatalyzes3steps:(1)theCO2isremoved,(2)NAD+isreducedto NADH,and(3)theremainingacetateislinkedwithCoenzymeAtoformAcetylCoA CoAisaderivativeofavitaminB5whosedeficiencycausesBeriberidisease. TheAcetylCoApossessesaveryhighenergybond(indicatedbyawavyline)that poisestheAcetylCoAatthetopoftheenergyhillandreadytogodownhillinthe subsequentreactionsofgradualstep-wiseoxidationthattheKrebscycleis. Itisacyclicpathwaythattakesplaceinsidethemitochondrialmatrix.All intermediatesarederivativesofcitricacid,atricarboxylicacid. Totalof8steps.Allexcept3arereversibl.e AcetylCoA,a2carbonmoleculeentersthecyclebycondensationwiththe4- carbonoxaloacetate.EachofthetwocarbonsofacetylCoAareoxidizedand removedasCO2intwoseparatereactions.Oxaloacetateisregenerated. 3moleculesofNAD+arereducedto3moleculesofNADH+H+ onemoleculeofFADisreducedtoFADH2 onemoleculeofGDPisphosphorylatedtoGTP.Thisiscalledsubstratelevel phosphorylation(asopposedtooxidativephosphorylation). o OxidationofpyruvatetoacetylCoAiscatalyzedbythepyruvate dehydrogenasecomplexinthemitochondria o Mitochondriaconsistofinnerandoutermembranesandthematrix o EnzymesofthePDHcomplexandtheTCAcycle(exceptsuccinate dehydrogenase)areinthematrix o Aspecialtransporterpresentintheinnermitochondrialmembraneallows entryofamoleculeofpyruvateinexchangeforahydroxideion o ThefirstreactionisanactivationofpyruvatebytheactionofthePyruvate Dehydrogenase(PDH)complex. o InPDHreactiononecarbonofpyruvateisoxidizedtoCO2andoneNADHis formed. 12 - o ThePDHstepisirreversible;asaresult,animalsarenotabletosynthesize glucosefromacetylCoA(fat) Overallreaction:AcetylCoA+3NAD++FAD+GDP+Pi+2H2O2CO2+CoASH+ 3NADH+2H++FADH2+GTP TheTCAcycleisregulatedatthe3irreversiblestepsconductedbytheenzymes citratesynthase,isocitratedehydrogenaseandα-ketoglutaratedehydrogenase. -AnabolicroleofTCAcycle. - IntermediatesoftheTCAcycleserveasprecursorsforbiosynthesisofvarious biomolecules - Manyaminoacidsaresynthesizedstartingwithtransaminationofα-ketoglutarate oroxaloacetate - PorphyrinsandhemearesynthesizedfromsuccinylCoA - Oxaloacetateisalsotheprecursorofpurinesandpyrimidines - Fattyacidsandsterolsaresynthesizedfromcitrate -Oxidativephosphorylation. - TheNADHandFADH2,formedduringglycolysis,β-oxidationandtheTCAcycle, giveuptheirelectronstoreducemolecularO2toH2O. - Electrontransferoccursthroughaseriesofproteinelectroncarriers,thefinal acceptorbeingO2;thepathwayiscalledastheelectrontransportchain,ETC. - ETCtakesplaceininnermitochondrialmembranewherealloftheelectroncarriers arepresent. 13 - ThefunctionofETCistofacilitatethecontrolledreleaseoffreeenergythatwas storedinreducedcofactorsduringcatabolism. Energyisreleasedwhenelectronsaretransportedfromhigherenergy NADH/FADH2tolowerenergyO2 ThisenergyisusedtophosphorylateADP. ThiscouplingofATPsynthesistoNADH/FADH2oxidationiscalledoxidative phosphorylation. Oxidativephosphorylationisresponsiblefor90%oftotalATPsynthesisinthecell. -TheChemiosmoticTheory - Explainsthemechanismofoxidativephosphorylation. - WhenelectronsaretransportedalongthecomponentsoftheETC,the accompanyingprotonsarereleased. - PartofthefreeenergyharvestedduringtheETCisusedtopumpprotonsoutofthe mitochondrialmatrix. - TheresultingunevendistributionofprotonsgeneratesapHgradientandacharge gradientacrosstheinnermitochondrialmembrane. - Theelectrochemicalpotentialenergygeneratedbythesegradientsiscalledas ProtonMotiveForce. - ThereturnofprotonstothemitochondrialmatrixiscoupledtoATPsynthesis. - ProtonsreturnthroughtheanintegralmembraneproteinATPsynthasethat harnessestheenergyoftheprotonstosynthesizeATPfromtheADTandinorganic phosphate. - ATPsynthaseisamultiplesubunitcomplexthatbindsADPandinorganic phosphateandconvertsthemtoATP - AsignificantamountofenergyisuseduptopumpH+outofthemitochondria.Only athirdisusedforATPsynthesis. -MitochondriaareBiochemicalHubs - ThemitochondrialmatrixcontainsenzymesofPDH,TCAcycle,β-oxidationand aminoacidoxidation. - Mitochondrialmatrixisenclosedbytwomembranes. - ComponentsoftheETCarelocatedontheinnermembrane;thefoldedcristae providealargesurfacearea. - Theinnermembraneishighlyimpermeableandrequiresspecifictransporters. - Transportersspecificforpyruvate,fattyacids,aminoacids,ATP/ADP,phosphate andprotonsarefoundintheinnermembrane. - Theoutermembraneispermeabletosmallmoleculesandionsduetothespecial transmembraneproteinsthatformchannelsintheoutermembrane. - Thereareproteinsspecializedtoinhibitoxidativephosphorylationbyuncoupling ETCfromoxidativephosphorylation.Uncouplerscarryprotonsacrossthe mitochondrialmembranemakingit‘leaky’forH+.ThepHandelectricalgradientis notgeneratedandATPisnotsynthesized. - Inthepresenceofanuncouplingagent,energyreleasedviatheETCisconverted intoheat. - Thismechanismisusedbyhibernatinganimalstostaywarminthewinter,since theydon’tneedATPforanabolicprocesseswhiletheyareresting. - Weusethismechanismtogenerateheatinourbrownfat. 14 -TransportofNADHintomitochondria - GlycolyticpathwayresultsinthereductionofNAD+toNADHinthecytosol - NADHisoxidizedtoNAD+bytheETCinthemitochondria - ThemitochondrialmembraneisimpermeabletoNADH,thus,atransportsystem wouldberequiredtoallowentrytoNADHintothemitochondrialmatrix - InsteadofNADHmoleculedirectlyenteringthemitochondria,thereareelectron shuttlesystemsthatacceptelectronsfromcytosolicNADH,entermitochondria, andgiveuptheelectronstoelectronacceptorsinthemitochondrialmatrix -CompleteOxidationofglucose - Completeoxidationofglucoseinvolvesthefollowingpathwaysandnetreactions: - Glycolysis:glucose+2ADP+2Pi+2NAD+2pyruvate+2ATP+2NADH+2H++ 2H2O - PDHcomplex:2pyruvate+2CoA+2NAD+2acetylCoA+2CO2+2NADH - TCAcycle:2acetylCoA+6NAD++2FAD+2GDP+2Pi+4H2O4CO2+6NADH+ 4H++2FADH2+2GTP+2CoA - Overalloxidation:glucose+2ADP+2GDP+4Pi+8NAD++2FAD+2H2O6CO2+ 2ATP+2GTP+8NADH+6H++2FADH2