Major cytochrome P450 enzyme responsible for oxidation of secondary alcohols to the corresponding ketones in mouse hepatic microsomes. Oxidation of 7-hydroxy-delta8-tetrahydrocannabinol to 7-oxo-delta8-tetrahydrocannabinol.

The oxidative activities of 7alpha- and 7beta-hydroxy-Delta8-tetrahydrocannabinol (7alpha- and 7beta-hydroxy-Delta8-THC) to 7-oxo-Delta8-THC in hepatic microsomes of mice were significantly increased by the treatment of mice with dexamethasone or phenobarbital. A cytochrome P450 enzyme, named P450MDX-B, was purified from hepatic microsomes of dexamethasone-treated mice, and its apparent molecular mass was estimated to be 51,000. The NH2-terminal amino acid sequence of P450MDX-B was the same as that of CYP3A11. The oxidative activities of 7alpha- and 7beta-hydroxy-Delta8-THC were 2.55 and 4.92 nmol/min/nmol P450, respectively. The antibody against P450MDX-B almost completely inhibited the oxidative activities of 7alpha- and 7beta-hydroxy-Delta8-THC in mice. These results indicate that P450MDX-B (CYP3A11) is a major enzyme responsible for the oxidation of 7alpha- and 7beta-hydroxy-Delta8-THC to 7-oxo-Delta8-THC in mouse liver.