胆固醇代谢与双重抑制PPT课件.ppt

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1、CholesterolMetabolismandtheConceptofDualInhibitionDavidE.Cohen,MD,PhDOverviewDigestivelipidmetabolismCholesterolbalanceInhibitorsofcholesterolsynthesisandabsorptionDualinhibitionDigestiveLipidMetabolismReverseCholesterolTransportBloodPeripheralTissuesLiverBileExcessCholesterolCholesterolCata

2、bolismintoBileSaltsCholateCholesterolCholesterol7-hydroxylaseHOHOOHCOO-OHBileSaltsBreakdownproductsofcholesterolAmphipathicmoleculesFunctiontotransportcholesterolinthedigestivesystemStructureofBiliaryandIntestinalMicellesCholesterolBileSaltPhospholipidFunctionsofMicellesTransportcholesterolfr

3、omtheliverintotheintestineviathebiliarytreeParticipateinfatdigestionandabsorptionBiliaryLipidSecretionSinusoidalMembraneBloodHepatocyteCanalicularMembraneBileSaltABCG5/G8CholesterolABCB4PhospholipidABCB11BileBiliaryLipidsDailySecretion(g)LipidClassBilesaltsPhospholipidsCholesterol24112BiliaryLi

4、pidTransportDuodenumJejunumIleumColonBiliaryTransportandStorageLiverFatDigestionDuodenumJejunumIleumColonBiliaryTransportandStorageLiverFatDigestionTriglyceridesDietaryCholesterolFattyAcids+MonoglyceridesFatAbsorptionDuodenumJejunumIleumBiliaryTransportandStorageColonLiverLymphEnterocyte

5、IntestinalLumenCholesterolAbsorptionCholesterolNPC1L1CholesterylEsterABCG5/G8ACATLymphEnterocyteIntestinalLumenTriglycerideAbsorption2FattyAcid+MonoglycerideDGATTriglycerideLymphEnterocyteIntestinalLumenChylomicronFormationCholesterylEsterCMapoB48TriglycerideCholesterolBalanceDuodenumJejunum

6、IleumColonPortalVenousReturn(>95%ofBiliarySecretion)Fecalexcretion(0.4g/d)BiliaryTransportandStorageLiverSynthesis0.4g/dSecretion24g/dEnterohepaticCirculationofBileSaltsDuodenumJejunumIleumColonBiliaryTransportandStorageFecalexcretion(1.2g/d)DietaryCholesterol(0.4g/d)Absorption~5

7、0%CMapoB48LiverBiliaryCholesterol(2g/d)BiliaryandDietaryCholesterolCholesterolBalanceDuodenumJejunumIleumColonBiliaryTransportandStorageCholesterolCholesterol(1.2g/d)+BileSalts(0.4g/d)DietaryCholesterol(0.4g/d)Loss(1.6g/d)