ISOTOPE EFFECT STUDIES ON THE MECHANISM OF THE CYTOCHROME-P-450IIA1-CATALYZED FORMATION OF DELTA-6-TESTOSTERONE FROM TESTOSTERONE

  • 1 November 1990
    • journal article
    • research article
    • Vol. 18  (6) , 974-979
Abstract
Testosterone metabolism by cytochrome P-450IIA1 results in four metabolites: 6.alpha.-hydroxytestosterone; 7.alpha.-hydroxytestosterone; 17.beta.-hydroxy-4,6-androstadiene-3-one (.DELTA.6-T); and 17.beta.-hydroxy-4,6-androstadiene-3-one-6,7-oxide. The epoxide is formed upon further oxidation of .DELTA.6-T, and its formation is in competition with the dissociation of .DELTA.6-T from the active site. The analysis of the KM and Vmax values, as well as the product ratios for testosterone and three selectively deuterated analogs, strongly suggest that .DELTA.6-testosterone formation occurs primarily by initial hydrogen atom abstraction at the 6.alpha.-position followed by abstraction of the 7.alpha.-hydrogen atom.

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