Effect of steroid biosynthesis modificators on the progesterone biotransformation by a recombinant yeasts expressing cytochrome P450c17

   


1. Research Institute for Physico-chemical Problems, Belarussian State University
2. nstitute of Microbiology, Dresden University of Technology
Type: Experimental/clinical study
UDK: 577.175.5      PubMed Id: 16898588
Year: 2006 vol: 52  issue:3  pages: 298-308
Abstract: Using the recombinant microorganisms S. cerevisiae GRF18 YEp5117α, expressing cytochrome P450c17 from bovine adrenal cortex, we investigated the influence of the various modificators of steroids biosynthesis on the relationship between the 17α-hydroxylation of progesterone and 20α-reduction. Dexamethasone and metirapon had no effect on the reaction of progesterone 17α-hydroxylation and on the reaction of 17α-hydroxyprogesterone 20α-reduction. Mifepriston and danazol did not covalently modify amino acid residues of the cytochrome P450c17 or its heme group under the conditions of the biotransformation of progesterone by recombinant yeasts. Ketokonazol, mifepriston and danazol acted as low-affinity competitive inhibitors, but the 20-dihydro derivatives of progesterone were mixed type inhibitors for the cytochrome P450c17. All modifiers that we used did not influence the functional properties of the yeast analog of 20α-hydroxysteroid dehydrogenase. According to the influence on the catalytic parameters of the cytochrome P450c17, the modifiers used can be arranged in the following order: 20β-dihydroprogesterone (maximum effect) > mifepriston = ketokonazol > 20α-dihydroprogesteron > danazol > dexamethasone, metirapon (without effect).
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Reference: Shkumatov V.M., Usova E.V., Frolova N.S., Barth G., Mauersberger S., Effect of steroid biosynthesis modificators on the progesterone biotransformation by a recombinant yeasts expressing cytochrome P450c17, Biomeditsinskaya khimiya, 2006, vol: 52(3), 298-308.
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