Cytochrome P450 3A9 catalyzes the metabolism of progesterone and other steroid hormones.
Cytochrome P450 3A9 catalyzes the metabolism of progesterone and other steroid hormones.
复制标题
细胞色素 P450 3A9 催化孕酮和其他类固醇激素的代谢。
DOI：
10.1023/a:1007124417566
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发表时间：
2000
影响因子：
4.3
通讯作者：
Strobel,HW
中科院分区：
文献类型：
--
作者：
Wang,H;Napoli,KL;Strobel,HW
用重组P450 3A 9蛋白研究了大鼠脑CYP 3A的雌性特异性异构体P450 3A 9在几种甾体激素代谢中的催化需求和作用。P450 3A 9的最佳类固醇激素羟化酶活性需要胆酸盐，而不是细胞色素b5。P450 3A 9在睾酮、雄烯二酮、孕酮和脱氢表雄酮（DHEA）的羟化反应中具有活性。在我们的复溶条件下，未检测到P450 3A 9对皮质醇的活性。在所有检测的类固醇激素中，雌性特异性P450 3A 9似乎最有效地催化孕酮（主要雌性激素之一）的代谢，形成三种单羟基化产物，6β-、16α-和21-羟基孕酮。我们的数据还表明，P450 3A 9可以催化由孕酮形成二羟基产物4-异戊烯-6 β，21-二醇-3，20-二酮，其转换数为1.3 nmol/min/nmol P450。根据P450 3A 9使用21-羟孕酮或6β-羟孕酮作为底物的Vmax/Km值，可以通过21-羟孕酮的6β-羟基化或6β-羟孕酮的21-羟基化来形成4-二烯-6 β，21-二醇-3，20-二酮。作为大鼠脑中表达的CYP 3A的主要亚型，P450 3A 9对两种主要神经甾体孕酮和DHEA的活性表明P450 3A 9可能在神经甾体代谢中发挥作用。
The catalytic requirements and the role of P450 3A9, a female-specific isoform of CYP3A from rat brain, in the metabolism of several steroid hormones were studied using recombinant P450 3A9 protein. The optimal steroid hormone hydroxylase activities of P450 3A9 required cholate but not cytochrome b5. P450 3A9 was active in the hydroxylation reactions of testosterone, androstenedione, progesterone and dehydroepiandrosterone (DHEA). No activity of P450 3A9 toward cortisol was detectable under our reconstitution conditions. Among all the steroid hormones examined, female-specific P450 3A9 seemed to catalyze most efficiently the metabolism of progesterone, one of the major female hormones, to form three mono-hydroxylated products, 6β-, 16α-, and 21-hydroxyprogesterone. Our data also showed that P450 3A9 can catalyze the formation of a dihydroxy product, 4-pregnen-6β, 21-diol-3, 20-dione, from progesterone with a turnover number, 1.3 nmol/min/nmol P450. Based on the Vmax/Kmvalues for P450 3A9 using either 21-hydroxprogesterone or 6β-hydroxyprogesterone as a substrate, 4-pregnen-6β, 21-diol-3, 20-dione may be formed either by 6β-hydroxylation of 21-hydroxprogesterone or 21-hydroxylation of 6β-hydroxyprogesterone. As a major isoform ofCYP3A expressed in rat brain, the activities of P450 3A9 toward two major neurosteroids, progesterone and DHEA suggested a possible role for P450 3A9 in the metabolism of neurosteroids.