Testosterone 1 beta-hydroxylation by human cytochrome P450 3A4

Eur J Biochem. 2004 Oct;271(19):3962-9. doi: 10.1111/j.1432-1033.2004.04339.x.

Abstract

Human cytochrome P450 3A4 forms a series of minor testosterone hydroxylation products in addition to 6 beta-hydroxytestosterone, the major product. One of these, formed at the next highest rate after the 6 beta- and 2 beta-hydroxy products, was identified as 1 beta-hydroxytestosterone. This product was characterized from a mixture of testosterone oxidation products using an HPLC-solid phase extraction-cryoprobe NMR/time-of-flight mass spectrometry system, with an estimated total of approximately 6 microg of this product. Mass spectrometry established the formula as C(19)H(29)O(3) (MH(+) 305.2080). The 1-position of the added hydroxyl group was established by correlated spectroscopy and heteronuclear spin quantum correlation experiments, and the beta-stereochemistry of the added hydroxyl group was assigned with a nuclear Overhauser correlated spectroscopy experiment (1 alpha-H). Of several human P450s examined, only P450 3A4 formed this product. The product was also formed in human liver microsomes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Baculoviridae / genetics
  • Chromatography, High Pressure Liquid
  • Cytochrome P-450 CYP3A
  • Cytochrome P-450 Enzyme System / metabolism*
  • Humans
  • Hydroxylation
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology*
  • NAD / metabolism
  • NADP / metabolism
  • Oxidation-Reduction
  • Testosterone / metabolism*

Substances

  • NAD
  • Testosterone
  • NADP
  • Cytochrome P-450 Enzyme System
  • CYP3A protein, human
  • Cytochrome P-450 CYP3A