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Proteinbreakdownstartsatstomach•OptimalpH1.5～2.5，•Lowspecificity•Producesmallpeptideandfreeaminoacidspepsinogen胃蛋白酶原+SmallPeptideHCl、PepsinPepsinBreakdownofdietaryproteinsEnterokinase肠激酶:producedbycellsoftheduodenum[du:ədi:nəm]ˌˈ（十二指肠）Synthesisoftheenzymesasinactiveprecursors---zymogen(酶原或前酶）:1Protectstheexocrinecellsfromdestructiveproteolyticattack.2Transportation3AllowRegulationElaboratemechanismforgettingactivedigestiveenzymes.ProteinDigestionProteolyticenzymesofpancreaticjuiceEndopeptidasesExopeptidasesTrypsin:Arg,Lys(C)Chymotrypsin:Tyr,Trp,Phe,Met,Leu(C)Elastase:Ala,Gly,Ser(C)carboxypeptidaseaminopeptidaseCleavagesitesandsubstratesofproteasesMARTKQTARKSTGGKAPRKQLATKAARKSAPSTGTwomajorsystemsfortheturnoverofcellularproteins:LysosomesandUbiquitin-mediatedproteindegradationProteinDegradationinCell1LysosomalhydrolasesexhibitacidicpHoptimal.2Lostactivityifleakedintocytosol.3Cathepsin组织蛋白酶家族LowspecificityLysosomalDegradationPathwayProteinsA.EndocytosedB.CytosolicC.Organellesbyautophagy溶酶体贮积病：基因突变致溶酶体酸性水解酶缺陷痛风：溶酶体破裂UbiquitinationUbactivatingenzyme(Uba)Ubconjugatingenzyme(Ubc)E3-UbLigaseWhatisUbiquitinandUbiquitylation?HumanUb:MQIFKVTLTGKTITLEVEPNDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLRLRGGYeastUb:MQIFKVTLTGKTITLEVESSDTIDNVKSKIQDKEGIPPDQQRLIFAGKQLEDGRTLSDYNIQKESTLHLVLRLRGG肽键和异肽键substrateUbMQIFKVTLTGKTITLEVEPNDTIENVKAKIQDKEGIPPDQQRLIFAGKQLEDGRTLADYNIQKESTLHLVLRLRGGUbiquitinpathwayE1-S-UbE2-S-UbE3substratesUbMono-ubiquitinationChange：proteinconformation,Localization,interactionPolyubiquitinationUbUbUbUbsubstratesProteosomeDegradationE1-Ubactivatingenzyme(Uba)UsesATPAMP+PPitoformthioesterbondbetweenitssulfhydrylgroupandtheterminalcarboxylategroupofUBE2-Ubconjugatingenzyme(Ubc):AcceptsactivatedUBE3-UbLigase:CatalyzestransferofUBfromE2to-aminogroupoflysineontargetproteinforminganisopeptidebond异肽键ATP蛋白质泛素化降解途径7要素Aminoacidmetabolism•Deamination（脱氨）•Transamination（...