Roles of cytochrome P450 2A6 in the oxidation of flavone, 4′-hydroxyflavone, and 4′-, 3′-, and 2′-methoxyflavones by human liver microsomes.

Nine forms of recombinant cytochrome P450 (P450 or CYP) enzymes were used to study roles of individual P450 enzymes in the oxidation of flavone and some other flavonoids, 4′-hydroxyflavone and 4′-, 3′-, and 2′-methoxyflavones, by human liver microsomes using LC-MS/MS analysis. As has been reported previously , 4′-, 3′-, and 2′-methoxyflavones were preferentially O-demethylated by human liver P450 enzymes to form 4′-, 3′-, and 2′-hydroxylated flavones and also 3′,4′-dihydroxyflavone from the former two substrates. In comparisons of product formation by oxidation of these methoxylated flavones, CYP2A6 was found to be a major enzyme catalysing flavone 4′- and 3′-hydroxylations by human liver microsomes but did not play significant roles in 2′-hydroxylation of flavone, O-demethylations of three methoxylated flavones, and the oxidation of 4′-hydroxyflavone to 3′,4′-dihydroxyflavone. The effects of anti-CYP2A6 IgG and chemical P450 inhibitors suggested that different P450 enzymes, as well as CYP2A6, catalysed oxidation of these flavonoids at different positions by liver microsomes. These studies suggest that CYP2A6 catalyses flavone 4′- and 3′-hydroxylations in human liver microsomes and that other P450 enzymes have different roles in oxidizing these flavonoids. [ABSTRACT FROM AUTHOR]