Indexed on: 10 Sep '95Published on: 10 Sep '95Published in: Archives of Biochemistry and Biophysics
Cytochrome P450 catalyzes monooxidation reactions of many organic compounds in the presence of hydroperoxides even in the absence of electron-transfer proteins and molecular oxygen. To understand the mechanism of the hydroperoxide-induced cytochrome P450 reactions, we investigated effects of ligands such as alcohols and imidazoles and 7-ethoxycoumarin, a substrate of cytochrome P450 1A2 (P450 1A2), on the cumyl hydroperoxide (CHP) O-O cleavage reaction with wild-type P450 1A2. Formation rates of cumyl alcohol from CHP with P450 1A2 were remarkably enhanced up to 25-fold by adding alcohols, whereas those of acetophenone were not changed by the same procedure. 2-Methylimidazole did not essentially influence the CHP reaction with P450 1A2, while 4-methylimidazole hampered the cumyl alcohol formation. 7-Ethoxycoumarin also impeded the cumyl alcohol formation with P450 1A2. These CHP reactions with P450 1A2 under various conditions are consistent with P450 1A2 spectral changes with CHP obtained under the same conditions. The present study suggests that the several ligands such as alcohols and imidazoles have marked effects on the heterolytic O-O cleavage reaction of CHP with P450 1A2. Mechanisms of the peroxide O-O scission with P450 1A2 associated with the distal site structure and substrate binding are discussed.