内分泌及代谢疾病课件.ppt

内分泌的分子生物学finalInsulinSynthesis内分泌的分子生物学finalInsulinStructureIn1958,FrederickSangerwasawardedhisfirstNobelPrizeinChemistryfordeterminingthesequenceoftheaminoacidsthatmakeupinsulin.Thismarkedthefirsttimethataproteinhadhadtheorderofitsaminoacids(theprimarysequence)determined.InsuliniscomposedoftwochainsofaminoacidsnamedchainA(21aminoacids)andchainB(30aminoacids)thatarelinkedtogetherbytwodisulfidebridges.Thereisa3rddisulfidebridgewithintheAchainthatlinksthe6thand11thresiduesoftheAchaintogether内分泌的分子生物学finalInsulinsecretionRisinglevelsofglucoseinsidethepancreaticcellstriggerthereleaseofinsulin胰腺?细胞内葡萄糖水平的升高触发胰岛素释放内分泌的分子生物学final1.Glucoseistransportedintothebetacellbytype2glucosetransporters(GLUT2).Onceinside,thefirststepinglucosemetabolismisthephosphorylationofglucosetoproduceglucose-6-phosphate.Thisstepiscatalyzedbyglucokinase--itistherate-limitingstepinglycolysis.葡萄糖6-磷酸葡萄糖葡萄糖激酶内分泌的分子生物学final2.Asglucosemetabolismproceeds,ATPisproducedinthemitochondria.葡萄糖代谢过程中,线粒体产生ATP内分泌的分子生物学final3.TheincreaseintheATP:ADPratioclosesATP-gatedpotassiumchannelsinthebetacellmembrane.Positivelychargedpotassiumions(K+)arenowpreventedfromleavingthebetacell.细胞内ATP:ADP比例增加，关闭?细胞ATP-钾通道，防止带正电的钾离子离开?细胞内分泌的分子生物学final4.Theriseinpositivechargeinsidethebetacellcausesdepolarization.?细胞内正电荷的增加引起细胞去极化内分泌的分子生物学final5.Voltage-gatedcalciumchannelsopen,allowingcalciumions(Ca2+)tofloodintothecell.钙离子通道开放，使细胞外的钙离子进入细胞内内分泌的分子生物学final6.Theincreaseinintracellularcalciumconcentrationtriggersthesecretionofinsulinviaexocytosis细胞内钙离子的增加触发胰岛素通过胞吐作用分泌到细胞外内分泌的分子生物学finalTherearetwophasesofinsulinreleaseinresponsetoariseinglucose.Thefirstisanimmediatereleaseofinsulin.Thisisattributabletothereleaseofpreformedinsulin,whichisstoredinsecret