Ethnic-related differences in coumarin 7-hydroxylation activities catalyzed by cytochrome P4502A6 in liver microsomes of Japanese and Caucasian populations

Article abstract of DOI:10.3109/00498259609046718

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.

Full text of DOI:10.3109/00498259609046718

Xenobiotica
the fate of foreign compounds in biological systems
ISSN: 0049-8254 (Print) 1366-5928 (Online) Journal homepage: http://www.tandfonline.com/loi/ixen20
Ethnic-related differences in coumarin 7-
hydroxylation activities catalyzed by cytochrome
P4502A6 in liver microsomes of Japanese and
Caucasian populations
T. Shimada, H. Yamazaki & F. P. Guengerich
To cite this article: T. Shimada, H. Yamazaki & F. P. Guengerich (1996) Ethnic-related
differences in coumarin 7-hydroxylation activities catalyzed by cytochrome P4502A6 in liver
microsomes of Japanese and Caucasian populations, Xenobiotica, 26:4, 395-403
To link to this article: http://dx.doi.org/10.3109/00498259609046718
Published online: 22 Sep 2008.
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Date: 31 January 2016, At: 21:37