PT - JOURNAL ARTICLE AU - K R Korzekwa AU - W F Trager AU - K Nagata AU - A Parkinson AU - J R Gillette TI - Isotope effect studies on the mechanism of the cytochrome P-450IIA1-catalyzed formation of delta 6-testosterone from testosterone. DP - 1990 Nov 01 TA - Drug Metabolism and Disposition PG - 974--979 VI - 18 IP - 6 4099 - http://dmd.aspetjournals.org/content/18/6/974.short 4100 - http://dmd.aspetjournals.org/content/18/6/974.full SO - Drug Metab Dispos1990 Nov 01; 18 AB - 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.