THE ROLE OF CYTOCHROME B(5) IN THE BIOSYNTHESIS OF ANDROGENS BY HUMAN P450C17
THE ROLE OF CYTOCHROME B(5) IN THE BIOSYNTHESIS OF ANDROGENS BY HUMAN P450C17
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DOI：
10.1006/abbi.1995.1173
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发表时间：
1995-03-10
影响因子：
3.9
通讯作者：
WATERMAN, MR
中科院分区：
文献类型：
--
作者：
KATAGIRI, M;KAGAWA, N;WATERMAN, MR
人细胞色素b(5)对纯化的人细胞色素P450c17催化的17，20-裂解酶活性有深远的影响。它将17-羟孕烯醇酮转化为脱氢表雄酮的能力提高了13倍，将17-羟孕酮转化为雄烯二酮的能力提高了至少10倍。在没有细胞色素b(5)的情况下，这种后一种活性几乎是检测不到的。P450c17催化的其他活性包括孕酮和孕烯醇酮的17α-羟基化，受细胞色素b(5)的影响要小得多。孕烯醇酮转化为17α-羟孕烯醇酮的转化率增加2倍，而孕酮转化为17α-羟孕酮的转化率保持不变。这些使用纯化系统的研究表明，细胞色素b(5)在调节P450c17的活性以优化性激素合成和糖皮质激素合成之间的平衡方面发挥作用。特别是，他们指出，在含有高b(5)/P450比率的人类睾丸中，17α-羟孕酮可以作为睾酮产生的中间产物，而不是一个死胡同，或者换一种说法，因为人类睾丸中细胞色素b(5)的浓度相对较高，Delta 4和Delta 5类固醇合成途径都可以导致睾酮的产生。(C)1995年学术出版社。
Human cytochrome b(5) has a profound effect on the 17,20-lyase activities catalyzed by purified, human cytochrome P450c17. It enhances the conversion of 17 alpha-hydroxypregnenolone to dehydroepiandrosterone by 13-fold and the conversion of 17 alpha-hydroxyprogesterone to androstenedione by at least 10-fold. This latter activity is virtually undetectable in the absence of cytochrome b(5). Other activities catalyzed by P450c17 include 17 alpha-hydroxylation of progesterone and pregnenolone and are much less influenced by cytochrome b(5). The conversion of pregnenolone to 17 alpha-hydroxypregnenolone is increased by 2-fold, while that of progesterone to 17 alpha-hydroxyprogesterone is unchanged. These studies using purified systems suggest that cytochrome b(5) plays a role in regulating the activities of P450c17 to optimize the balance between sex hormone synthesis and glucocorticoid synthesis. In particular, they indicate that in human testes which contains a high b(5)/P450 ratio, 17 alpha-hydraxyprogesterone can serve as an intermediate in testosterone production, rather than being a dead-end product, or stated another way, because of the relatively high concentration of cytochrome b(5) in the human testis, both the Delta 4 and the Delta 5 steroidogenic pathways can lead to testosterone production. (C) 1995 Academic Press, Inc.