Stereochemistry of the Microsomal Glutathione S-Transferase-Catalyzed Addition of Glutathione to Chlorotrifluoroethene in Isolated Rat Hepatocytes
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 Configuration Cetyltrimethylammonium Chloride Cysteine Conjugate Electrophilic Substrate Cytosolic Glutathione
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