Xenobiotica p. 395 - 403 (1996)
Update date:2022-08-11
Topics:
Shimada
Yamazaki
Guengerich
Interethnic differences in cytochrome P4502A6 (CYP2A6) levels and coumarin 7-hydroxylation activities were determined in liver microsomes of 30 Japanese and 30 Caucasians. Although CYP2A6 levels and coumarin 7-hydroxylation activities varied very significantly in the 60 human samples examined, both CYP2A6 levels and coumarin 7-hydroxylation activities were found to be higher in Caucasian than Japanese population. Interestingly, eight of the 30 Japanese examined showed very low or undetectable levels of coumarin 7-hydroxylation activities as well as of CYP2A6 in liver microsomes. All of the Caucasians, however, had significant CYP2A6 levels and variable 7-hydroxylation activities. Kinetic analysis of coumarin 7-hydroxylation activities in liver microsomes of various human samples suggested that although there were ~260-fold differences in V(max)'s in 10 human samples examined, the K(m)'s were very similar (2.1 ± 0.7 μM); a value consistent with that obtained (1.2 μM) with purified CYP2A6 in reconstituted system. The results suggest that CYP2A6 is actually involved in the 7-hydroxylation of coumarin in human liver microsomes, and that interethnic differences in coumarin 7-hydroxylation activities in Japanese and Caucasian population may be ascribed to the differences in expression of CYP2A6 protein.
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