PMID: 9182869Jan 1, 1997Paper

Pregnenolone-7beta-hydroxylating activity of human cytochrome P450-1A1

The Journal of Steroid Biochemistry and Molecular Biology
J DoostzadehR Morfin

Abstract

In many human and murine tissues, both pregnenolone and dehydroepiandrosterone are hydroxylated at the 7alpha and 7beta positions by a cytochrome P450-containing microsomal complex. The 7alpha- and 7beta-hydroxysteroids produced were shown to activate an immune response in mice. Based upon identification by crystallization to constant specific activity and gas chromatography-mass spectrometry analysis, we ascertained that a yeast-expressed human cytochrome P450-1A1 was able to 7beta-hydroxylate pregnenolone (K(M) from 3.2 +/- 0.5 to 4.1 +/- 0.4 microM, turnover number from 117 +/- 15 to 135 +/- 13 pmol/min/nmol of cytochrome P450-1A1). The other human cytochromes P450 tested did not produce identifiable quantities of 7alpha- or 7beta-hydroxylated derivatives of pregnenolone or dehydroepiandrosterone. These findings indicate that cytochrome P450-1A1 involvement in the 7beta-hydroxylation of pregnenolone may contribute to the production of the 7-hydroxylated steroids necessary for activation of the immune defences.

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Citations

Oct 20, 2001·Toxicology Letters·Y L WongS E Welty
Aug 1, 1997·The Journal of Steroid Biochemistry and Molecular Biology·A C CotillonR Morfin
Feb 25, 1999·The Journal of Steroid Biochemistry and Molecular Biology·O LapcíkL Stárka
Jan 5, 2000·The Journal of Steroid Biochemistry and Molecular Biology·T Kołek
Aug 21, 2003·Comparative Biochemistry and Physiology. Toxicology & Pharmacology : CBP·R PetkamJ F Leatherland
Dec 13, 2006·Drug Metabolism and Drug Interactions·Sonia Chalbot, Robert Morfin
May 9, 2002·Drug Metabolism Reviews·Slobodan Rendic
May 23, 2006·The Journal of Steroid Biochemistry and Molecular Biology·Caroline MullerRobert Morfin
May 29, 2009·Expert Opinion on Drug Metabolism & Toxicology·Yan-Yan Zhang, Ling Yang
Apr 11, 2006·The Journal of Steroid Biochemistry and Molecular Biology·Caroline MullerRobert Morfin

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