7.UGTsPhaseII.ppt - NS120/220 Glucuronidation and UGTs O HN...

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NS120/220 Glucuronidation and UGTs O O OH OH COO - P OH OH O O P OH O OH CH 2 O OH HN N O O O
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Learning Objectives Defne Phase II reactions. Describe the high energy co-Factor in glucoronidation and explain their role in biotransFormation reactions. Describe the reaction mechanisms oF Glucuronidation. Explain how you could determine the substrate specifcity oF UGTs. Describe the three diseases oF unconjugated hyperbilirudinemia and what kinds oF mutations cause these diseases.
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Readings HUMAN UDP-GLUCURONOSYLTRANSFERASES : Metabolism, Expression, and Disease, Annu. Rev. Pharmacol. Toxicol. 2000. 40:581–616
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General Scheme of Xenobiotic Metabolism Lipophilic Hydrophilic Metabolism Increase excretability Decrease biological activity Phase I (oxidative) Parent compound Metabolites polarity functionality Phase II (synthetic) Metabolites size ionization water solubility
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Transferred Group
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Estimated contribution of different Phase II enzymes to xenobiotic conjugation glutathione
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7.UGTsPhaseII.ppt - NS120/220 Glucuronidation and UGTs O HN...

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