Metabolism of Glutathione S-Conjugates: Multiple Pathways

Many potentially toxic electrophilic xenobiotics and some endogenous compounds are detoxified by conversion to the corresponding glutathione S-conjugate, which is metabolized to the N-acetylcysteine S-conjugate (mercapturate) and excreted. Some mercapturate pathway components, however, are toxic. Bioactivation (toxification) may occur when the glutathione S-conjugate (or mercapturate) is converted to a cysteine S-conjugate that undergoes a β-lyase reaction. If the sulfhydryl-containing fragment produced in this reaction is reactive, toxicity may ensue. Some drugs and halogenated workplace/environmental contaminants are bioactivated by this mechanism. On the other hand, cysteine S-conjugate β-lyases occur in nature as a means of generating some biologically useful sulfhydryl-containing compounds.