生物化學(xué)教學(xué)課件：Chapter 12 Metabolic integration and regulation

Chapter12MetabolicintegrationandregulationSectionⅠ.Thecharactersofmetabolism1.Integration2.Canberegulated3.Eachtissueandorganhasindividualmetaboliccharacter4.Commonmetabolicpool5.ATPisthecommonformforenergystorageandutilization6.NADPHisthereducingequivalentsforbiosynthesismetabolism

CH3COSCoA

2HETC

H2OTACCO2ADP+PiATPGlucoseFatProteinSectionⅡInterconnectionofMetabolismI.EnergymetabolismATP/ADPisastheregulatorysignal.II.Interconnectionofcarbohydrates,lipidsandproteinsmetabolismSectionⅢLiverfunctioninmetabolismAnatomicalandmetabolicfeaturesofliverDualbloodsupply:hepaticarteryandportalvein;Dualoutputsystem:hepaticveinandbileduct;Alargenumberofhepaticsinusoid(肝血竇);Hepaticcellsarerichincellularorganelleandenzymes.FunctionsofliverinmetabolismIncarbohydratemetabolismInlipidsmetabolismInproteinmetabolismInvitaminmetabolismInhormonemetabolismStabilizingbloodglucoselevelsby:GlycogenesisConversionofglucosetofatGlycogenolysisGluconeogenesis(AAs,glycerol,lactate…)Ketonebodies(FAs)

Therolesofliverincarbohydratemetabolism不同營(yíng)養(yǎng)狀態(tài)下肝內(nèi)如何進(jìn)行糖代謝？飽食狀態(tài)：肝糖原合成↑過(guò)多糖則轉(zhuǎn)化為脂肪，以VLDL形式輸出肝糖原分解↑補(bǔ)充血糖以糖異生為主脂肪動(dòng)員↑→酮體合成↑→節(jié)省葡萄糖饑餓狀態(tài)：空腹?fàn)顟B(tài)：Therolesofliverinlipidmetabolism*Digestionandabsorption:cholesterol→bileacids*Anabolism:Liveristhemainplaceforthesynthesisoffat,phospholipidandcholesterol

*Catabolism:Liverhasastrongabilitytotakeandtooxidizefattyacidsandsynthesizeketonebodiesspecifically.*Transportation:Liveristhemainorgantoassemblelipoproteins(VLDLandHDL)andtodisassemblelipoproteins(CMremnant,LDLandHDL).TherolesofliverinproteinmetabolismSynthesisandsecretionofmanykindsofplasmaproteins:albumin,thrombinogen,fibrinogen,apoproteins,globulins...CleanupofmanykindsofplasmaproteinsMetabolismofmanykindsofaminoacidsCleanupofammoniabyureacycleCleanupofamine

AbsorptionoffatsolublevitaminStorevitaminsA,E,KandB12.TransportationofvitaminsA,DTransformationofVitamins(→Coenzymes)VitPP→NAD+andNADP+pantothenicacid→HSCoAcarotene→VitAVitB1→TPPVitD3→25(OH)VitD3TherolesofliverinvitaminmetabolismLiverhaveimportantactionsinthe

Transformation

Degradation

Therolesofliverinhormoneinactivation蜘蛛痣（spidernevus）

肝掌（liverpalm）

SectionⅣ.Metaboliccharactersofdifferenttissuesandorgans1.Heart(aerobicoxidation)Theheartusesavarietyoffuels:fattyacids,ketonebodies,lactate,glucose.2.BrainUndernormalconditionsthebrainonlyusesbloodglucose.Duringfasting

usesketonebodies.3.Muscle

GlycogenesisandstoresPhosphocreatin,Glycogenolysis,FAoxidationtoprovideenergylacksglucose–6-phosphatase,cannotreleasefreeGlc4.Matureredbloodcell

Glycolysisintheerythrocyteisthemostprominentpathway.5.Adiposetissue

MajortissueforresynthesisandstorageofTG.TGlipasebreakdownTGintofattyacidandglycerol.6.Kidney

Gluconeogenesisat

celllevel

(original)athormonelevel

at

entiretylevelSectionⅤ.RegulationofmetabolismMetabolicregulation

atdifferentlevels:SeparateddistributionofenzymesincellⅠ.Regulationatcelllevel

主要代謝途徑酶系的細(xì)胞內(nèi)分布多酶體系分布多酶體系分布DNA及RNA合成蛋白質(zhì)合成糖原合成脂酸合成膽固醇合成磷脂合成血紅素合成尿素合成細(xì)胞核內(nèi)質(zhì)網(wǎng)、胞液胞液胞液內(nèi)質(zhì)網(wǎng)、胞液內(nèi)質(zhì)網(wǎng)胞液、線粒體胞液、線粒體糖酵解磷酸戊糖途徑糖異生脂酸氧化多種水解酶三羧酸循環(huán)氧化磷酸化呼吸鏈胞液胞液胞液線粒體溶酶體線粒體線粒體線粒體MetabolicregulationFastregulationSlowregulationAllostericregulationChemicalmodificationsynthesisdegradationRegulatoryenzymeKeyenzymeRate-limitingenzyme*MetabolicpathwayactiveactiveⅡ.MetabolicregulationathormonelevelBindingofhormoneswiththeirspecificreceptorsresultsinspecificmetabolicchangesinthetargetcells.Thehormonescanbeclassifiedintotwotypes:HormonesbindingwithmembranereceptorHormonesbindingwithintracellularreceptorSteroidhormones,VitaminD3,ThyroidhormoneRetinoidsAseriesofmetabolicchangeⅢ.RegulationatentiretylevelNeuroendocrinesystem1.SatiationSatiation

→Insulin↑glucagon↓(1)Glucosesupplyenergy;(2)Glucose→Glycogen(liver,muscle)；(3)Glucose→TG(VLDL)（1）Aftereating6～8h,Liverglycogenolysis↑（2）Aftereating16～24h,Gluconeogenesis↑Fatmobilization↑Ketonebody↑

Proteinbreakdown↑2.Fasting3.StarvationShorttermstarvation:(1)Fatmobilization↑,ketonebodies↑(2)Gluconeogenesisinliver↑,aminoacids,glycerol,lactate(3)Proteinbreakdown↑(4)Theheart,muscle,kidneyandbrainadaptstoreducedglucoselevelsbyincreasingtheuseoffattyacidsandketonebodiesasalternativeenergysubstrates.insulin↓,glucagon↑1.LipidmetabolismFatmobilization↑↑2.Carbohydratemetabolismgluconeogenesis↑3.Proteinmetabolism