Glutathione, gamma-glutamyl transpeptidase, and the mercapturic acid pathway as modulators of 2-bromohydroquinone oxidation.
Glutathione (GSH) conjugates of 2-bromohydroquinone are more difficult to oxidize than the parent hydroquinone. Hydrolysis catalyzed by gamma-glutamyl transpeptidase (gamma-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 gamma-GT to facilitate quinol oxidation by catalyzing the formation of the labile cysteine conjugate may have important biological consequences. Cells exhibiting high gamma-GT activity may be predisposed to the potentially toxic effects of quinol-thioethers.
Monks
T J
TJ
Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas, Austin 78712.
Lau
S S
SS
D000111:Acetylcysteine / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006873:Hydroquinones / Q000378:metabolism*; D010084:Oxidation-Reduction; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D006873:Hydroquinones; C042377:2-bromohydroquinone; D005723:gamma-Glutamyltransferase; D005978:Glutathione; D000111:Acetylcysteine