Ohmori S, Nakasa H, Asanome K, Kurose Y, Ishii I, Hosokawa M, Kitada M
Division of Pharmacy, Chiba University Hospital, 1-8-1 Inohana, Chuo-ku, Chiba 260, Japan.
Biochim Biophys Acta. 1998 May 8;1380(3):297-304. doi: 10.1016/s0304-4165(97)00156-6.
The catalytic properties of CYP3A7 in the metabolism of endogenous and exogenous substrates were compared with those of CYP3A4 and CYP3A5 using COS-7 expressing enzymes. The highest activities of dehydroepiandrosterone (DHEA) and dehydroepiandrosterone 3-sulfate (DHEA-S) 16alpha-hydroxylase were observed in COS-7 cells expressing CYP3A7. In contrast, the activity of testosterone 6beta-hydroxylase of CYP3A7 expressed in COS-7 cells was much less than that of CYP3A4 expressed in COS-7 cells. The rate of carbamazepine 10, 11-epoxidation was the greatest in COS-7 cells expressing CYP3A4, followed by CYP3A5 and CYP3A7. On the other hand, the formation of reductive metabolite of zonisamide was the highest in COS-7 cells expressing CYP3A4, followed by CYP3A7 and CYP3A5. Furthermore, the addition of triazolam resulted in a decrease in 6beta-hydroxylation catalyzed by CYP3A7, but not by CYP3A4, whereas the pretreatment of microsomes with triacetyloleandomycin (TAO) resulted in a decrease in the reaction catalyzed by CYP3A4, but not by CYP3A7. Together with these results, it was suggested that CYP3A7 exerts differential catalytic properties not only in metabolism of endogenous substrates but also in drug metabolism compared to CYP3A4 and CYP3A5.
使用表达酶的COS-7细胞，比较了CYP3A7在内源性和外源性底物代谢中的催化特性与CYP3A4和CYP3A5的催化特性。在表达CYP3A7的COS-7细胞中观察到脱氢表雄酮（DHEA）和硫酸脱氢表雄酮（DHEA-S）16α-羟化酶的最高活性。相比之下，在COS-7细胞中表达的CYP3A7的睾酮6β-羟化酶活性远低于在COS-7细胞中表达的CYP3A4的活性。在表达CYP3A4的COS-7细胞中，卡马西平10,11-环氧化的速率最大，其次是CYP3A5和CYP3A7。另一方面，在表达CYP3A4的COS-7细胞中，唑尼沙胺还原代谢产物的形成最高，其次是CYP3A7和CYP3A5。此外，添加三唑仑导致CYP3A7催化的6β-羟化反应减少，但CYP3A4催化的反应未减少，而用三乙酰夹竹桃霉素（TAO）预处理微粒体导致CYP3A4催化的反应减少，但CYP3A7催化的反应未减少。综合这些结果，表明与CYP3A4和CYP3A5相比，CYP3A7不仅在内源性底物代谢中，而且在药物代谢中都发挥着不同的催化特性。
