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首页> 外文期刊>Life sciences >METABOLISM OF DELTA(9)-TETRAHYDROCANNABINOL BY CYTOCHROME P450 ISOZYMES PURIFIED FROM HEPATIC MICROSOMES OF MONKEYS
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METABOLISM OF DELTA(9)-TETRAHYDROCANNABINOL BY CYTOCHROME P450 ISOZYMES PURIFIED FROM HEPATIC MICROSOMES OF MONKEYS

机译：猴肝微粒体中细胞色素P450同工酶对δ（9）-四氢大麻酚的代谢

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摘要

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. [References: 22]
机译：与猴子肝脏微粒体形成的Delta（9）-四氢大麻酚（Delta（9）-THC）代谢最丰富的是11-OH-Delta（9）-THC，其次是8 alpha-OH-，8 beta-OH-和3'-OH-Delta（9）-THC。从猴肝微粒体中纯化了两种细胞色素P450同工酶P450RM-A和P450JM-C，发现其分子量为51,000。在重构系统中，P450RM-A形成11-OH-，8 alpha-OH-，8 beta-OH-和3'-OH-Delta（9）-THC的活性为19-，40-，22分别比肝微粒体的相应活性高10倍和10倍。 P450JM-C形成3'-OH-Delta（9）-THC的活性比P450RM-A高10倍，而11和8α-羟基化的同工酶活性却不高不同的是，P450RM-A中的8个β-羟基化活性比P450JM-C高14倍。针对P450RM-A和P450JM-C的抗体分别显着抑制11-OH-和8 alpha-OH-Delta（9）-THC和3'-OH-Delta（9）-THC的微粒体形成。这些结果表明，P450RM-A和P450JM-C是主要的同工酶，分别负责11-OH-和8 alpha-OH-Delta（9）-THC和3'-OH-Delta（9）-THC的形成。 ，在猴子中。 [参考：22]

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