RT Journal Article
SR Electronic
T1 Metabolic activation of phenol by human myeloperoxidase and horseradish peroxidase.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 674
OP 679
VO 30
IS 6
A1 D A Eastmond
A1 M T Smith
A1 L O Ruzo
A1 D Ross
YR 1986
UL http://molpharm.aspetjournals.org/content/30/6/674.abstract
AB The oxidation of phenol catalyzed by human myeloperoxidase and horseradish peroxidase resulted in extensive binding of phenol-derived metabolites to boiled rat liver protein. This binding paralleled closely the removal of phenol from the incubations and was inhibited from 83 to 99% by the addition of the antioxidants, ascorbate and glutathione, suggesting that metabolism and binding were occurring via a one-electron oxidation pathway. Metabolic studies employing both human myeloperoxidase and horseradish peroxidase resulted in the identification of 4,4'-biphenol and diphenoquinone as the principal identifiable metabolites. The addition of reduced glutathione to incubations containing horseradish peroxidase resulted in the formation of two conjugate species. These conjugate species were identified by fast atom bombardment mass spectrometry to be glutathione conjugates of diphenoquinone. The major gluthathione conjugate was identified as 3-(glutathion-S-yl)-4,4'-biphenol by NMR spectroscopy. These results suggest that the formation of highly reactive species through the peroxidase-mediated metabolism of phenol and other phenolic compounds could play an important role in the hematopoietic toxicity observed during chronic benzene exposure.