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Matsunaga T, Iwawaki Y, Watanabe K, Yamamoto I, Kageyama T, Yoshimura H.
“Metabolism of delta 9-tetrahydrocannabinol by cytochrome P450 isozymes purified from hepatic microsomes of monkeys”.
Life Sci. 1995 Jun;56(23-24):2089-95.
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Abstract
The most abundant metabolite of delta 9-tetrahydrocannabinol (delta 9-THC) formed with hepatic microsomes of monkeys was 11-OH-delta 9-THC, followed by 8 alpha-OH-, 8 beta-OH- and 3'-OH-delta 9-THCs. Two cytochrome P450 isozymes, P450RM-A and P450JM-C, were purified from monkey hepatic microsomes and found to have a molecular weight of 51,000. In the reconstituted system, the activities of P450RM-A towards formation of 11-OH-, 8 alpha-OH-, 8 beta-OH- and 3'-OH-delta 9-THCs were 19-, 40-, 22- and 10-fold higher, respectively, than the corresponding activities of the hepatic microsomes. The activity of P450JM-C towards formation of 3'-OH-delta 9-THC was 10-fold higher than that of P450RM-A, while the activities of both isozymes for 11- and 8 alpha-hydroxylation were not so much different and the 8 beta-hydroxylation activity was 14-fold higher in P450RM-A than in P450JM-C. Antibodies against P450RM-A and P450JM-C markedly inhibited the microsomal formation of 11-OH- and 8 alpha-OH-delta 9-THCs, and 3'-OH-delta 9-THC, respectively. These results suggest that P450RM-A and P450JM-C are major isozymes responsible for the formation of 11-OH- and 8 alpha-OH-delta 9-THCs, and 3'-OH-delta 9-THC, respectively, in monkeys.
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