Metabolic activation of phenol by human myeloperoxidase and horseradish peroxidase.
Eastmond-DA; Smigh-MT; Ruzo-LO; Ross-D
Mol Pharmacol 1986 Dec; 30(6):674-679
The peroxidase mediated metabolism of phenol (108952) by human myeloperoxidase (MPO) and horseradish-peroxidase (HRO) was examined. MPO was prepared from human neutrophils. Phenol at 500 micromolar was incubated with 10 micrograms/milliliter HRO or 1.5 units/milliliter MPO, and 1 millimolar hydrogen-peroxide in phosphate buffer at 37 degrees-C. During metabolism catalyzed by human MPO and HRO, phenol was converted to highly reactive protein binding species. The mechanism of this conversion was thought to involve the formation of a free radical intermediate. The addition of ascorbate and glutathione inhibited the binding from 83 to 99%, which suggested that metabolism and binding were occurring via a one electron oxidation pathway. When reduced glutathione was added to incubations containing HRO two conjugate species were formed and identified as glutathione conjugates of diphenoquinone. The formation of 4,4'-biphenol and diphenoquinone resulted from the peroxidase mediated metabolism of phenol. Diphenoquinone was one of the binding species. The authors suggest that the formation of these highly reactive species could be significant in the hematopoietic toxicity which is observed on chronic exposure to benzene (71432).
NIOSH-Publication; NIOSH-Grant; Training; Analytical-chemistry; Enzyme-activity; Metabolic-study; Metabolic-activation; Hydrocarbons; Blood-disorders; Hematopoietic-system; Toxic-effects; In-vitro-studies;
Biomedical & Environ Hlth Scis University of California 322 Warren Hall Berkeley, Calif 94720
University of California Berkeley, Berkeley, California