Glutathione, γ-glutamyl transpeptidase, and the mercapturic acid pathway as modulators of 2-bromohydroquinone oxidation

Abstract

Glutathione (GSH) conjugates of 2-bromohydroquinone are more difficult to oxidize than the parent hydroquinone. Hydrolysis catalyzed by γ-glutamyl transpeptidase (γ-GT), however, results in the formation of the corresponding cysteine conjugate which is more readily oxidized than the parent hydroquinone. N-Acetylation of the cysteine conjugate to yield the mercapturate regenerates a compound that is more stable to oxidation than either the parent quinol or its cysteine conjugate. Thus, 2-bromohydroquinone oxidation is exquisitely modulated via GSH conjugation and its metabolism through the mercapturic acid pathway. The ability of γ-GT to facilitate quinol oxidation by catalyzing the formation of the labile cysteine conjugate may have important biological consequences. Cells exhibiting high γ-GT activity may be predisposed to the potentially toxic effects of quinol-thioethers.