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Beaune PH, Kremers PG, Kaminsky LS, De Graeve J, Albert A, Guengerich FP: Comparison of monooxygenase activities and cytochrome P-450 isozyme concentrations in human liver microsomes. Drug Metab Dispos. 1986 Jul-Aug;14(4):437-42. 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: there are important variations in the amounts of the three cytochrome P-450 isozymes measured, particularly P-450 (8) and P-450 (9); aldrin epoxidase, d-benzphetamine N-demethylase, and S-warfarin 4-hydroxylase activities are linked to cytochrome P-450 (5); aryl hydrocarbon (benzo (a) pyrene) hydroxylase and 4-nitroanisole-O-demethylase activities are linked to P-450 (8); hydroxylations at the 4'-, 6-, 7-, and 8-positions of R-warfarin are closely linked to each other but are not correlated with other measured monooxygenase activities or P-450 isozyme levels; and P-450 (9) 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 cytochromes P-450 in drug metabolism in man which can be further examined using in vitro and in vivo methods. |
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