Testosterone 1 beta-hydroxylation by human cytochrome P450 3A4

European Journal of Biochemistry
Joel A KrauserF P Guengerich

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.

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Citations

Apr 6, 2007·Analytical Chemistry·Raymundo Sanchez-Ponce, F Peter Guengerich
Aug 8, 2009·Nature Protocols·Christal D SohlF Peter Guengerich
Jul 10, 2012·The Journal of Biological Chemistry·Qian ChengF Peter Guengerich
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May 4, 2006·Chembiochem : a European Journal of Chemical Biology·Amandine ChefsonKarine Auclair
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