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E N D Presentation Transcript PHASE II DRUG METABOLISM: Glucuronidation and Sulfation General properties of Phase II metabolism Introduction to glucuronidation Substrates for UGTs UGT structure Properties of glucuronides Methods to characterize glucuronides Disposition and reactions of glucuronides UGT pharmacogenetics, polymorphism, variability Sulfotransferases N-Acetylation, Aminoacid conjugation, Glutathione conjugation Smith, Phase II Metabolism, UNC Chapel Hill, 8/2012 Recommended Reading: Gonzales and Tukey, Drug Metabolism, In: Goodman and Gilmans, The Pharmacological Basis of Therapeutics, 11th Edition, 2005, Chapter 3

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Antioxidants are REQUIRED to prevent excess free radicals which lead to oxidative stress Free Radicals & Oxidative Stress What are free radicals and oxidative stress

L-cystine is reduced in the BBB, and the resulting cysteine is transported out of the endothelial cells into the brain via L-type amino acid transporter 1 (LAT1) (Snchez del Pino et al., 1995)