Cytochrome P450 2A6 and other human P450 enzymes in the oxidation of flavone and flavanone

<p>1. We previously reported that flavone and flavanone interact spectrally with cytochrome P450 (P450 or CYP) 2A6 and 2A13 and other human P450s and inhibit catalytic activities of these P450 enzymes. In this study, we studied abilities of CYP1A1, 1A2, 1B1, 2A6, 2A13, 2C9 and 3A4 to oxidize flavone and flavanone.</p> <p>2. Human P450s oxidized flavone to 6- and 5-hydroxylated flavones, seven uncharacterized mono-hydroxylated flavones, and five di-hydroxylated flavones. CYP2A6 was most active in forming 6-hydroxy- and 5-hydroxyflavones and several mono- and di-hydroxylated products.</p> <p>3. CYP2A6 was also very active in catalyzing flavanone to form 2′- and 6-hydroxyflavanones, the major products, at turnover rates of 4.8 min<sup>−1</sup> and 1.3 min<sup>−1</sup>, respectively. Other flavanone metabolites were 4′-, 3′- and 7-hydroxyflavanone, three uncharacterized mono-hydroxylated flavanones and five mono-hydroxylated flavones, including 6-hydroxyflavone. CYP2A6 catalyzed flavanone to produce flavone at a turnover rate of 0.72 min<sup>−1</sup> that was ∼3-fold higher than that catalyzed by CYP2A13 (0.29 min<sup>−1</sup>).</p> <p>4. These results indicate that CYP2A6 and other human P450s have important roles in metabolizing flavone and flavanone, two unsubstituted flavonoids, present in dietary foods. Chemical mechanisms of P450-catalyzed desaturation of flavanone to form flavone are discussed.</p>