6. Module+4+Xenobiotic+metabolism+Phase+2+and+3 (2).pdf -...

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Molecular and Cellular ToxicologySpring 2019Phase 2 Metabolism (Conjuga5on Reac5ons)IntroductionThe introduc-on of a polar group into a molecule may give the substance a sufficiently hydrophiliccharacter for rapid excre-on. For most substances, however, this is not the case and a subsequentreac-on is requiredTypes of Phase II ReactionsVBSC/BMB 43360OOHOOHOHOHCOOHObenzenebenzene epoxidephenolphenylglucuronideoriomonitoroooofortpoorENmonthsMorrmodifiedsugarrErKmumbBIfmorof
Molecular and Cellular ToxicologySpring 2019Glucuronic Acid ConjugationGlucuronide Forma5onGlycogen synthesis differs from glycogen breakdown. Unlike breakdown, synthesis is endergonic,meaning that glycogen is synthesized without the input of energy. Energy for glycogen synthesis comesfrom UTP, which reacts with glucose-1-phosphate, forming UDP-glucose, in reac-on catalysed by UDP-glucose pyrophosphorylase. Glycogen is synthesized from monomers of UDP-glucose by the enzymeGlycogen synthase, which progressively lengthens the glycogen chain. As glycogen synthase can onlylengthen an exis-ng chain, the protein glycogenin is needed to ini-ate the synthesis of glycogen.General Reac5onsExamplesVBSC/BMB 43361Glucose-1-P + UTPUDP-glucoseGlycogen + PPiUDP-glucosedehydrogenasePyrophosphorylaseNAD+NADH + H+OOUDPCOOHOHOHOHUDP-glucuronic AcidOH+NNOOHOOHOHCH2OPOPOOOOOOCOOHOHOHOHUDPGAPhenolOCOOHOHOHOHO+ UDPPhenylglucuronideconjugatingmoleenvymedomyconjugationaformconjugateegeneralnon'sµptEEEIdetoxifyingpathwayGlucegonenationfhodeosideimakethiscofactorIcofactorbindingpocketsns.awwnnosyitmnsarusecuafemymereleasecropunenetrutyfinalconjugateabletobeexcretedforputtransportsaysshowmeaglucuronicandIen
Molecular and Cellular ToxicologySpring 2019Human UDP-glucuronosyltransferase enzymesCurrently, 15 human UGT cDNAs have been iden-fied eight UGT1A proteins encoded by the UGT1Alocus and seven proteins encoded by UGT2 genes.Localiza5on of UGTsVBSC/BMB 43362gexesconfogatedrawoneofthestructnsRxnthertcanoccorconjugationonomatchetgotgoofedggangtobeconsidermetabolitescannemanyofUGTSyssitesseedifftypsofstructuresCYPIAIworkssomehowGrenefamlyresAlotufventdudedbysequencebittotalej.wsmostinvertfamilygepfofferV2oaths09ItUGT2UnexpresseddrawneonateswarunexenenirIts1congrgatrycorsettiformtmftransporters9fp.qpymyqgyma.mycofactorsynthesuedersaposal
Molecular and Cellular ToxicologySpring 2019Sulfate ConjugationIntroduc5onSulfate conjuga-on was one of the first pathways studied for xenobio-c metabolism. It is nowrecognized as a biotransforma-on route for many endogenous and xenobio-c compounds. Theadenosine-containing cofactor PAPS is the universal metabolic donor of sulfate groups.

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Term
Fall
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Tags
Glutathione, Cellular Toxicology

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