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Download Lecture 11 (Parker) - Department of Chemistry ::: CALTECH
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ATP=cellularenergy Howdoesthecellextractenergyandreducingpowerfrom itsenvironment? Howdoesacellsynthesizethebuildingblocksofits macromoleculesandthenbuildthemacromolecules? Metabolism/intermediarymetabolism: Numberofreac@onsislargebutthekindsofreac@onsare small 5Basicprinciplesofmetabolism: 1)Fuelsaredegradedandlargemoleculesareconstructed stepbystepinaseriesoflinkedreac@ons 2)TheenergycurrencycommontoalllifeisATP 3)Theoxida@onofcarbonfuelspowerstheforma@onof ATP 4)Manymetabolicpathwayshowever,thereareonlya limitednumberoftypesofreac@ons 5)Metabolicpathwaysare@ghtlyregulated Phototrophsarephotosynethicorganismsthatobtainenergybytrappingsunlight Chemotrophsobtainenergybyoxida@onoffoodstuffs Metabolicpathways: Someconvertenergyfromfuelstousefulformsothersrequireenergytoproceed 1) CatabolicreacBons: 2) FuelstoCO2+H20+energy 3) AnabolicreacBons: 4) Synthesisoffats,glucoseandDNArequireenergy Athermodynamicallyunfavorablereac@oncanbedrivenbya favorablereac@on: A=B+C+5kcal B=D-8kcal A=C+D-3kcal Bycouplingthereac@ontothefavorableB=Dstepthisdrives theoverallconversionofAtoCandD ATPhasahighphosphoryl-transferpoten@al Resonancestabiliza@onoforthophosphate ATPhasasmallnumberofsuchstructureswhereasADPandorthophosphatehavemany Othercompoundswithhighphosphoryl-transferpotenBal: ATPisintermediateinenergywhichallowsittofunc@onefficientlyasacarrierof phosphorylgroups ATPandcreaBnephosphatearetheiniBalenergysourcesthenmetabolismmustresupplyATP ATP-ADPCycle Theul@mateelectronacceptorintheoxida@onofCisO2;themorereduceda carbonistobeginwiththemorefreeenergyreleasedbyitsoxida@on: Fatsaremoreefficientfuelsourcethancarbohydratesbecausethecarbon infatsismorereduced: G3Pisametaboliteofglucoseandoxida@onofthisaldehydetothe acidreleasesenergy Theforma@onofATPfromG3Poccursintwosteps;thefirstoxida@onstep requiresNAD+andHPO4resul@nginaphosphorylatedintermediate1,3-BPG: ThesecondstepADPisphosphorylatedtoATPwiththe1,3-BGP phosphategroup: ProtonGradientsacrossmembranesarecreatedbytheoxida@onofcarbonfuels pumpingprotonsoutresul@ngintheinfluxofprotonsthroughanATP-synthesizing enzyme(redcomplex)andthesynthesisofATPfromADP Thediges@onoffoodresultsinthegenera@onofafewsimpleunitsthatplay akeyroleinmetabolism NADisamajorelectroncarrierintheoxida@onoffuels NAD+Nico@namideadeninedinucleo@deR=H NADPNico@namideadeninedinucleo@dephosphateR=P Intheoxida@onofasubstrate,thenico@namideringofNAD+acceptsahydrogen ionandtwoelectronsgenera@ngthereducedformasNADH Thisisadehydrogena@onreac@on Theothermajorelectroncarrieristhecoenzymeflavinadeninedinucleo@deFAD andFADH2 FADconsistsofaflavinmononucleo@de(blue)andanAMPunit(black) TheelectronsandprotonsarecarriedbytheisoalloxazineringcomponentofFAD: Reduc@vebiosynthesisusesNADPHastheelectrondonornotNADHwhichisused forATPgenera@on CoenzymeAisacarrierofacetylgroupsthroughathioesterbond Thehydrolysisoftheacetylgroupgenerates-7kcal Itisusedinthecatabolismoffa`yacidsandthesynthesisofmembranelipids NADH,NADPHandFADH2reactslowlywithO2 LikewiseATPandacetylCoAarehydrolyzedslowlywithoutacatalyst Thestabilityofthesemoleculesallowthemtocontroltheflowoffree energyandreducingpower Theexistenceofarecurringsetofac@vatedcarriersinallorganismsisa unifyingthemeinbiochemistry Manyac@vatedcarriersarederivedfromvitamins Vitaminsareorganicmoleculesthatareneededinsmall amountsinthedietsofhigheranimalsashigheranimalshave lostthecapacitytosynthesizethesemoleculesduringthe courseofevoluBon E.Colicanthriveonglucoseandorganicsalts,humansrequire atleast12vitaminsintheirdiet.Thebiosysnthesisofvitamins isoRencomplexrequiringmanysteps;itiseasiertoacquire thesenutrientsinthedietthantosynthesizethemdenovo Notallvitaminsfunc/onascoenzymesthosewithle5erdesigna/onhaveadiverse arrayoffunc/ons Therearethousandsofmetabolicreac@ons,buttheycanbesubdividedintosix types: Oxida@on-reduc@onreac@ons Liga@onreac@ons Isomeriza@onreac@ons Group-transferreac@ons Hydroly@creac@ons Func@onalgroupsmaybeaddedtodoublebondstoformsinglebondsorremoved fromsinglebondstoformdoublebonds Theenzymesthatperformthissteparecalledlyases Acri@calstepinglycolysisadehydra@onreac@on Metabolismiscontrolledby: 1) Theamountofenzymes 2) Theircataly@cac@vi@es 3) Theaccessibilityofsubstrates ADPisanancientmoduleinmetabolism