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Glutathione conjugation as a bioactivation reaction

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Author: Bladeren, P.J. van
Type:article
Date:2000
Institution: Centraal Instituut voor Voedingsonderzoek TNO
Source:Chemico-Biological Interactions, 1-2, 129, 61-76
Identifier: 56919
doi: doi:10.1016/S0009-2797(00)00214-3
Keywords: Nutrition · Bioactivation · Glutathione conjugates · Glutathione S-transferases · Cysteine · Glutathione · Glutathione transferase · Lyase · Catalysis · Chemical binding · Chemical reaction · Chromosomal localization · Conjugation · Covalent bond · Detoxification · Enzyme activation · Enzyme activity · Enzyme induction · Enzyme inhibition · Enzyme mechanism · Gene location · Genetic polymorphism · Human · Nonhuman · Protein expression · Reaction analysis · Reduction · Animals · Biotransformation · Carbon-Sulfur Lyases · Enzyme Induction · Glutathione · Glutathione Transferase · Humans · Metabolic Detoxication, Drug · Oxidation-Reduction · Xenobiotics

Abstract

In general, glutathione conjugation is regarded as a detoxication reaction. However, depending on the properties of the substrate, bioactivation is also possible. Four types of activation reaction have been recognized: direct-acting compounds, conjugates that are activated through cysteine conjugate beta-lyase, conjugates that are activated through redox cycling and lastly conjugates that release the original reactive parent compound. The glutathione S-transferases have three connections with the formation of biactivated conjugates: they catalyze their formation in a number of cases, they are the earliest available target for covalent binding by these conjugates and lastly, the parent alkylating agents are regularly involved in the induction of the enzymes. Individual susceptibility for each of these agents is determined by individual transferase subunit composition and methods are becoming available to assess this susceptibility. © 2000 Elsevier Science Ireland Ltd. Chemicals/CAS: Carbon-Sulfur Lyases, EC 4.4.-; Glutathione Transferase, EC 2.5.1.18; Glutathione, 70-18-8; S-alkylcysteine lyase, EC 4.4.1.6; Xenobiotics