Download Lecture 11 (Parker) - Department of Chemistry ::: CALTECH

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Transcript
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