Biol. Pharm. Bull. 28(4) 646—651 (2005)

stituent of marijuana, Cannabis sativa L. It is well known that THC is oxidized to a number of metabolites in the liver of mammals. Recent studies have clarified that P450 plays a major role in the oxidation of THC. We have previously reported that a hepatic microsomal enzyme, named microsomal alcohol oxygenase (MALCO), is able to oxidize 7aand 7b-hydroxy-D-THC to 7-oxo-D-THC in the presence of NADPH and molecular oxygen. We have purified CYP3A8 as a major enzyme of MALCO from hepatic microsomes of monkey. The activity was stereoselective and the rate of conversion of 7b-hydroxy-D-THC to 7-oxo-D-THC was higher than that from 7a-hydroxy-D-THC. In general, the P450-dependent monooxygenase system has an absolute requirement for NADPH. A few studies have indicated that NADH can also accelerate the oxidative metabolism of p-nitrophenetole and p-nitroanisole, and the bioactivation of 2-acetylaminofluorene and nitrosoamines. During our studies on the microsomal oxidative metabolism of D-THC, we observed that 7b-hydroxy-D-THC was effectively biotransformed to 7-oxo-DTHC by using NADH as a cofactor, without NADPH (Fig. 1). The present study was undertaken to define the basic characteristics of the microsomal NADH-mediated oxidation of 7b-hydroxy-D-THC to 7-oxo-D-THC in the liver of monkeys and compare it to the NADPH-dependent systems. MATERIALS AND METHODS