ENANTIOTOPIC SELECTIVITY OF CYTOCHROME P450-CATALYZED OXIDATIVE DEMETHYLATION OF METHOXYCHLOR - ALTERATION OF SELECTIVITY DEPENDING ON ISOZYMES AND SUBSTRATE CONCENTRATIONS

Oxidative demethylation of methoxychlor catalyzed by liver microsomes from a phenobarbital-treated rat produced the monodemethylated metabolite, the enantiomeric composition of which depended upon the initial substrate concentrations (N. Kurihara and A, Oku, Pestle. Biochem. Physiol. 40, 227 (1991)). The four isozymes of cytochrome P450 purified from phenobarbital-induced rat liver microsomes could be classified into two groups: one with higher enantiotopic selectivity and higher affinity for the substrate and the other with lower selectivity and affinity. When an appropriate combination of the purified two isozymes was used in a reconstituted system to catalyze the reaction, the dependence of the enantiotopic selectivity of the microsomal reaction upon the initial substrate concentrations was reproduced. (C) 1995 Academic Press. Inc.