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Role of microsomal steroid hydroxylases in Δ7-steroid biosynthesis

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Abstract

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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Abbreviations

ALA:

5-aminolevulinic acid

AND:

androstendione

CPR:

NADPH-dependent cytochrome P450-reductase

CYP17:

steroid 17α-hydroxylase/17,20-lyase

CYP21:

steroid 21-hydroxylase

DCS:

11-deoxycortisol

DHEA:

dehydroepiandrosterone

DOC:

deoxycorticosterone

DTT:

dithiothreitol

7dhC:

7-dehydrocholesterol

7dhP5:

7-dehydropregnenolone

7dh17OHP5:

7-dehydro-17α-hydroxypregnenolone

IPTG:

isopropyl-β-D-thiogalactopyranoside

K d :

dissociation constant

17OHP4:

17α-hydroxyprogesterone

17OHP5:

17α-hydroxypregnenolone

P4:

progesterone

P5:

pregnenolone

PMSF:

phenylmethylsulfonyl fluoride

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Authors and Affiliations

  1. Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, ul. Kuprevicha 5/2, 220141, Minsk, Belarus

    T. A. Sushko, A. A. Gilep, A. V. Yantsevich & S. A. Usanov

Authors
  1. T. A. Sushko
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  2. A. A. Gilep
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  3. A. V. Yantsevich
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  4. S. A. Usanov
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Correspondence to T. A. Sushko.

Additional information

Published in Russian in Biokhimiya, 2013, Vol. 78, No. 3, pp. 375–384.

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Sushko, T.A., Gilep, A.A., Yantsevich, A.V. et al. Role of microsomal steroid hydroxylases in Δ7-steroid biosynthesis. Biochemistry Moscow 78, 282–289 (2013). https://doi.org/10.1134/S0006297913030103

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