MAJOR CYTOCHROME-P450 ENZYME RESPONSIBLE FOR OXIDATION OF SECONDARY ALCOHOLS TO THE CORRESPONDING KETONES IN MOUSE HEPATIC MICROSOMES - OXIDATION OF 7-HYDROXY-DELTA(8)-TETRAHYDROCANNABINOL TO 7-OXO-DELTA(8)-TETRAHYDROCANNABINOL

The oxidative activities of 7 alpha- and 7 beta-hydroxy-Delta(8)-tetra hydrocannabinol (7 alpha- and 7 beta-hydroxy-Delta(8)-THC) to 7-oxo-De lta(8)-THC in hepatic microsomes of mice were significantly increased by the treatment of mice with dexamethasone or phenobarbital. A cytoch rome P450 enzyme, named P450MDX-B, was purified from hepatic microsome s of dexamethasone-treated mice, and its apparent molecular mass was e stimated to be 51,000. The NH2-terminal amino acid sequence of P450MDX -B was the same as that of CYP3A11. The oxidative activities of 7 alph a- and 7 beta-hydroxy-Delta(8)-THC were 2.55 and 4.92 nmol/min/nmol P4 50, respectively. The antibody against P450MDX-B almost completely inh ibited the oxidative activities of 7 alpha- and 7 beta-hydroxy-Delta(8 )-THC in mice. These results indicate that P450MDX-B (CYP3A11) is a ma jor enzyme responsible for the oxidation of 7 alpha- and 7 beta-hydrox y-Delta(8)-THC to 7-oxo-Delta(8)-THC in mouse liver.