Role of the Well-Known Basic and the Recently Discovered Acidic Glutathione S-Transferases in the Control of Genotoxic Metabolites
Glutathione S-transferases (GSTs; E.C. 2. 5. 1. 18) are a family of enzymes which have increasingly attracted the interest of toxicologists, pharmacologists, biochemists and clinicians since their discovery in 1961 (1). Initially, GSTs were believed to serve as intracellular transport proteins for endogenous compounds with limited solubility in water, thus acting as an intracellular equivalent to albumin in blood plasma. In this assumed capacity of reversible binding and transport of various ligands, the corresponding protein was named ligandin (2). Following the discovery of abundant GST occurrence in most forms of aerobic life including plants, and the GST-catalysed conjugation of a wide variety of elec-trophilic substrates with glutathione, GSTs are now generally considered to play a crucial role in the detoxification of foreign compounds such as mutagens, carcinogens and other noxious chemicals (for reviews see Refs. 3–6) by conjugation to glutathione. In addition, GSTs are believed to provide cellular protection by covalent binding of reactive electrophiles to the enzyme, which results in immobilization and inactivation of the compound in question.
KeywordsPolycyclic Aromatic Hydrocarbon Glutathione Transferase Ethacrynic Acid Cumene Hydroperoxide Microsomal Epoxide Hydrolase
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