lect 9 GSTPhaseII+ver2.ppt

lect 9 GSTPhaseII+ver2.ppt - NS120/220 GSTs and Glutathione...

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Unformatted text preview: NS120/220 GSTs and Glutathione Learning Objectives Describe the reaction mechanisms of Glutathione conjugation. Explain how GST conjugation is used to enable excretion Describe how the structure of GSTs help to understand their function. Describe how Brussels sprouts may protect against cancer. Readings John D. Hayes, Jack U. Flanagan, and Ian R. Jowsey (2005) Glutathione Transferases. Annu. Rev. Pharmacol. Toxicol . 45, 5188. 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 Transferred Group Glutathione Conjugation NH 2 CH- OOC CH 2 CH 2 C NH CH CH 2 C NH CH 2 COO- SH O O A tripeptide Glutamic acid (Glu) Glycine (Gly) Cysteine(Cys) Glutathione Transferases Five classes, alpha, mu, pi, theta, and zeta A1-A4, M1-M5, P1, T1-2, Z1 Soluble cytosolic enzymes, dimers Very high expression, 4% of all protein in liver also in intestine, kidney, lungs >95% cytosolic, 5% sER Typical substrates Organic halides, e.g methyl iodide, benzyl chloride Alkenes e.g. diethyl maleate Epoxides Mutation Research 482 (2001) 2126 Electrophilic heteroatoms (O, N, and S). (O, N, and S)....
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This note was uploaded on 03/09/2011 for the course NSI 20 taught by Professor Vulpe during the Spring '11 term at University of California, Berkeley.

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lect 9 GSTPhaseII+ver2.ppt - NS120/220 GSTs and Glutathione...

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