The role of cytochrome b5 in the biosynthesis of androgens by human P450c17.

Katagiri M, Kagawa N, Waterman MR
Arch Biochem Biophys. 1995 317 (2): 343-7

PMID: 7893148 · DOI:10.1006/abbi.1995.1173

Human cytochrome b5 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 b5. Other activities catalyzed by P450c17 include 17 alpha-hydroxylation of progesterone and pregnenolone and are much less influenced by cytochrome b5. 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 b5 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 b5/P450 ratio, 17 alpha-hydroxyprogesterone 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 b5 in the human testis, both the delta 4 and the delta 5 steroidogenic pathways can lead to testosterone production.

MeSH Terms (17)

17-alpha-Hydroxypregnenolone 17-alpha-Hydroxyprogesterone Aldehyde-Lyases Androgens Androstenedione Cell Membrane Cytochrome P-450 Enzyme System Cytochromes b5 Dehydroepiandrosterone Escherichia coli Humans Hydroxyprogesterones Kinetics Pregnenolone Progesterone Recombinant Proteins Steroid 17-alpha-Hydroxylase

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