Stereochemistry of the Microsomal Glutathione S-Transferase-Catalyzed Addition of Glutathione to Chlorotrifluoroethene in Isolated Rat Hepatocytes

Abstract

Glutathione S-transferases catalyze the nucleophilic addition of glutathione to electrophilic substrates. Glutathione S-conjugate formation, followed by conversion to mercapturates, serves to detoxify potentially harmful xenobiotics. Alternatively, glutathione S-conjugate formation is an important bioactivation mechanism for several classes of compounds (Anders et al., 1988). The nephrotoxicity of several haloalkenes, including chlorotrifluoroethene (CTFE), is attributable to glutathione S- conjugate formation, metabolism of the glutathione S-conjugate to the corresponding cysteine S-conjugate, translocation to the kidney, and bioactivation by cysteine conjugate β-lyase (Figure 1).KeywordsAbsolute ConfigurationCetyltrimethylammonium ChlorideCysteine ConjugateElectrophilic SubstrateCytosolic GlutathioneThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.