Metabolism of hydroquinone by human myeloperoxidase: mechanisms of stimulation by other phenolic compounds.
Hydroquinone, a metabolite of benzene, is converted by human myeloperoxidase to 1,4-benzoquinone, a highly toxic species. This conversion is stimulated by phenol, another metabolite of benzene. Here we report that peroxidase-dependent hydroquinone metabolism is also stimulated by catechol, resorcinol, o-cresol, m-cresol, p-cresol, guaiacol, histidine, and imidazole. In order to gain insights into the mechanisms of this stimulation, we have compared the kinetics of human myeloperoxidase-dependent phenol, hydroquinone, and catechol metabolism. The specificity (Vmax/Km) of hydroquinone for myeloperoxidase was found to be 5-fold greater than that of catechol and 16-fold greater than that of phenol. These specificities for myeloperoxidase-dependent metabolism inversely correlated with the respective one-electron oxidation potentials of hydroquinone, catechol, and phenol and suggested that phenol- and catechol-induced stimulation of myeloperoxidase-dependent hydroquinone metabolism cannot simply be explained by interaction of hydroquinone with stimulant-derived radicals. Phenol (100 microM), catechol (20 microM), and imidazole (50 mM) did, however, all increase the specificity (Vmax/Km) of hydroquinone for myeloperoxidase, indicating that these three compounds may be stimulating hydroquinone metabolism by a common mechanism. Interestingly, the stimulation of peroxidase-dependent hydroquinone metabolism by other phenolic compounds was pH-dependent, with the stimulating effect being higher under alkaline conditions. These results therefore suggest that the interaction of phenolic compounds, presumably by hydrogen-bonding, with the activity limiting distal amino acid residue(s) or with the ferryl oxygen of peroxidase may be an important contributing factor in the enhanced myeloperoxidase-dependent metabolism of hydroquinone in the presence of other phenolic compounds.
Subrahmanyam
V V
VV
Department of Biomedical and Environmental Health Sciences, School of Public Health, University of California, Berkeley 94720.
Kolachana
P
P
Smith
M T
MT
D001665:Binding Sites; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006873:Hydroquinones / Q000378:metabolism*; D007700:Kinetics; D008954:Models, Biological; D009504:Neutrophils / Q000201:enzymology*; D009195:Peroxidase / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D013379:Substrate Specificity
D006873:Hydroquinones; D010636:Phenols; D009195:Peroxidase; C031927:hydroquinone