Regulation of CHO Metabolism.ppt

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1、1,Regulationofglycolysis,1.WhenATPlevelsaresufficient,glycolysisactivitydecreasesHexokinaseinhibitedbyexcessglucose6-phosphatePFK-1isinhibitedbyATPandcitratePyruvatekinaseisinhibitedbyATP2.WhenATPisneeded,glycolysisisactivatedAMP(theproductofATPconsumption)relievetheinhibitionofPFK-1byATPFructose2,6

2、-bisphosphate(F2,6BP)relievetheinhibitionofPFK-1byATPPyruvatekinaseisactivatedbyF1,6BP,Step1,Step3,Step10,2,RegulationofHexokinase,HexokinasereactionismetabolicallyirreversibleG6P(product)levelsincreasewhenglycolysisisinhibitedatsitesfurtheralonginthepathwayG6PinhibitshexokinaseisozymesI,IIandIIItha

3、tareactiveatnormalglucoseconcentrations(Kmvalues10-6to10-4M)Glucokinase(hexokinaseIV,Km10-2M)formsG6Pintheliver(forglycogensynthesis)whenglucoseisabundant(activityismodulatedbyfructosephosphatesandaregulatoryprotein),3,RegulationofPFK-1,ATPisasubstrateandanallostericinhibitorofPFK-1AMPallosterically

4、activatesPFK-1byrelievingtheATPinhibition(ADPisalsoanactivatorinmammaliansystems)ChangesinAMPandADPconcentrationscancontrolthefluxthroughPFK-1Elevatedlevelsofcitrate(indicateamplesubstratesforcitricacidcycle)alsoinhibitPFK-1,4,RegulationofPFK-1byFructose2,6-bisphosphate(F2,6BP),F2,6-BPisapotentactiv

5、atorofPFK-1F2,6-BPisformedfromF6Pbyphosphofructokinase-2(PFK-2),whichisabi-functionalenzyme,b-D-Fructose2,6-bisphosphate,5,Hormoneglucagonisreleasedfromthepancreaswhenbloodglucoselevelsarelow,PFK-2isbi-functional,GlucagonslowsglycolysisGlucagoninducesglucosesynthesisandconversiontoglucosefromglycoge

6、n,Effectofglucagononliverglycolysis,6,RegulationofPyruvateKinase,FourPKisozymesexistinmammaliantissuesPKisallostericallyactivatedbyF1,6BP,inhibitedbyATPGlucagonstimulatesproteinkinaseAwhichphosphorylatesPKconvertingittoalessactiveform(liverandintestinalcells),ActivatorF1,6BP(red)boundwithPK,7,ThePas

7、teurEffect,Underanaerobicconditionstheconversionofglucosetopyruvateismuchhigherthanunderaerobicconditions(yeastcellsproducemoreethanolandmusclecellsaccumulatelactate)ThePasteurEffectistheslowingofglycolysisinthepresenceofoxygenMoreATPisproducedunderaerobicconditionsthanunderanaerobicconditions,there

8、forelessglucoseisconsumedaerobically,8,RegulationofGluconeogenesis,9,RegulationoftheTCAcycle,10,RegulationofGlycogenbreakdown,11,Conformationalchangesinglycogenphosphorylase,Tstate:activesiteblockedbyloop;Arg569lessavailableforsubstratebindingRstate:rotationofsubunitstoachievemorefavorablepacking;loopdisorderedsoactivesiteaccessible;Arg569rotatedsothataffinityforsubstrateincreased,12,Controlofglycogenmetabolisminmuscle,