COMPARISON OF MONOOXYGENASE ACTIVITIES AND CYTOCHROME-P-450 ISOZYME CONCENTRATIONS IN HUMAN-LIVER MICROSOMES

  • 1 July 1986
    • journal article
    • research article
    • Vol. 14  (4) , 437-442
Abstract
Concentrations of three human liver microsomal cytochrome P-450 isozymes and 20 different monooxygenase activities were determined in human liver microsomal preparations. The results of correlation analysis suggest that: a) there are important variations in the amounts of the three cytochrome P-450 isozymes measured, particularly P-4508 and P-4509; b) aldrin epoxidase, d-benzphetamine N-demethylase, and S-warfarin 4-hydroxylase activities are linked to cytochrome P-4505; c) aryl hydrocarbon (benzo(a)pyrene) hydroxylase and 4-nitroanisole-O-demethylase activities are linked to P-4508; d) hydroxylations at the 4''-, 6-, 7-, and 8-positions of R-warfarin are closely linked to each other but not correlated with other measured monooxygenase activities or P-450 isozyme levels; and e) P-4509 is not related to any of the catalytic activities tested. Thus, certain monooxygenase activities can be attributed to specific cytochrome P-450 isozymes. This approach should be useful in suggesting the roles of different cytochrome P-450 in drug metabolism in man which can be further examined using in vitro and in vivo methods.