Transferases glutathione conjugation

Glutathione 5-transferases Glutathione conjugation Cytosolic and Microsomal Glutathione 2 Yes... 

Oakley AJ, Lo Bello M, Mazzetti AP, Federici G, Parker MW. The glutathione conjugate of ethacrynic acid can bind to human pi class glutathione transferase Pl-1 in two different modes. FEES Lett 1997 419 32-6. 

Dekant W, Martens G, Vamvakas S, et al. 1987. Bioactivation of tetrachloroethylene. Role of glutathione S-transferase-catalyzed conjugation versus cytochrome P-450-dependent phospholipid alkylation. Drug Metab Dispos Biol Fate Chem 15 702-709. 

Srivastava SK, Singhal SS, Hu X et al. Differential catalytic efficiency of allelic variants of human glutathione S-transferase Pi in catalyzing the glutathione conjugation of thiotepa. Arch Biochem Bio-phys 1999 366 89-94. 

Thiol conjugation Epoxides Glutathione S-transferases (glutathione or N-acetylcysteine) Glutathione or N-acetyl cysteine thioethers... 

Schistosoma japonica glutathione-S -transferase [24] Conjugate addition of thiols to enones -300 HPLC... 

Glutathione conjugation Glutathione (GSH) GSH-S-transferase (cytosol, microsomes) Epoxides, arene oxides, nitro groups, hydroxylamines Acetaminophen, ethacrynic acid, bromobenzene... 

The oxidation of naphthalene was one of the earliest examples of an epoxide as an intermediate in aromatic hydroxylation. The epoxide can rearrange nonenzymatically to yield predominantly 1-naph-thol, interact with the enzyme epoxide hydrolase to yield the dihydrodiol, or interact with glutathione S-transferase to yield the glutathione conjugate, which is ultimately metabolized to a mer-capturic add. 

Figure 4.64 Glutathione-mediated activation of 1, 2-dibromoethane. The addition of glutathione is catalyzed by glutathione transferase. Loss of bromide from the glutathione conjugate gives rise to an episulfonium ion. This can react with bases such as guanine in DNA.

Cmarik, J.L., Inskeep, P.B., Meredith, M.J., Meyer, D.J., Ketterer, B. Guengerich, F.P. (1990) Selectivity of rat and human glutathione S-transferases in activation of ethylene dibromide by glutathione conjugation and DNA binding and induction of unscheduled DNA synthesis in human hepatocytes. Cancer Res., 50, 2747-2752... 

Usta M, Wortelboer HM, Yervoort J, Boersma MG, Rietjens IM, van Bladeren PJ, Cnubben NH. 2007. Human glutathione S-transferase-mediated glutathione conjugation of curcumin and efflux of these conjugates in Caco-2 cells. Chem Res Toxicol 20 1895-1902. 

Phase II Reactions. As with phase I reactions, phase II reactions usually depend on several enzymes with different cofactors and different prosthetic groups and, frequently, different endogenous cosubstrates. All of these many components can depend on nutritional requirements, including vitamins, minerals, amino acids, and others. Mercapturic acid formation can be cited to illustrate the principles involved. The formation of mercapturic acids starts with the formation of glutathione conjugates, reactions catalyzed by the glutathione -transferases. 

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