Role of Microsomal Steroid Hydroxylases in Δ⁷-Steroid Biosynthesis

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T. A. Sushko^*, A. A. Gilep, A. V. Yantsevich, and S. A. Usanov

Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, ul. Kuprevicha 5/2, 220141 Minsk, Belarus; fax: +375 (172) 637-274; E-mail: sushko-tatjana@rambler.ru; agilep@iboch.bas-net.by

^* To whom correspondence should be addressed.

Received July 5, 2012; Revision received October 31, 2012

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CYP17 (steroid 17α-hydroxylase/17,20-lyase) is a key enzyme in steroid hormone biosynthesis. It catalyzes two independent reactions at the same active center and has a unique ability to differentiate Δ⁴-steroids and Δ⁵-steroids in the 17,20-lyase reaction. The present work presents a complex experimental analysis of the role of CYP17 in the metabolism of 7-dehydrosteroids. The data indicate the existence of a possible alternative pathway of steroid hormone biosynthesis using 7-dehydrosteroids. The major reaction products of CYP17 catalyzed hydroxylation of 7-dehydropregnenolone have been identified. Catalytic activity of CYP17 from different species with 7-dehydropregnenolone has been estimated. It is shown that CYP21 cannot use Δ⁵-Δ⁷ steroids as a substrate.

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KEY WORDS: cytochrome P450, CYP17, CYP21, 7-dehydrosteroids, steroid hormone biosynthesis

DOI: 10.1134/S0006297913030103

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