Ethnic-related differences in coumarin 7-hydroxylation activities catalyzed by cytochrome P4502A6 in liver microsomes of Japanese and Caucasian populations
Ethnic-related differences in coumarin 7-hydroxylation activities catalyzed by cytochrome P4502A6 in liver microsomes of Japanese and Caucasian populations
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DOI：
10.3109/00498259609046718
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发表时间：
1996-04-01
期刊：
影响因子：
1.8
通讯作者：
Guengerich, FP
中科院分区：
文献类型：
--
作者：
Shimada, T;Yamazaki, H;Guengerich, FP
1.比较了30名日本人和30名高加索人肝微粒体细胞色素P4502A6(CYP2A6)水平和香豆素7-羟化活性的种族差异。虽然在所研究的60个人类样本中，CYP2A6水平和香豆素7-羟化活性有非常显著的差异，但高加索人的CYP2A6水平和香豆素7-羟化活性都高于日本人。有趣的是，在接受检查的30名日本人中，有8人显示出非常低或检测不到的香豆素7-羟化活性以及肝微粒体中的CYP2A6水平。然而，所有的高加索人都有显著的CYP2A6水平和可变的7-羟化活性。香豆素7-羟化活性的动力学分析表明，虽然10个人肝微粒体的V-max相差260倍，但K-m非常相似(2.1+/-0.7µM)，与重组体系中纯化的CYP2A6得到的值(1.2µM)一致。这些结果表明，人肝微粒体中的香豆素7-羟基化实际上参与了CYP2A6的表达，日本人和高加索人香豆素7-羟化活性的种族差异可能归因于其蛋白表达的差异。
1. Interethnic differences in cytochrome P4502A6 (CYP2A6) levels and coumarin 7-hydroxylation activities were determined in liver microsomes of 30 Japanese and 30 Caucasians.2. Although CYP2A6 levers 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.3. 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.4. Kinetic analysis of coumarin 7-hydroxylation activities in liver microsomes of various human samples suggested that although there were similar to 260-fold differences in V-max's in 10 human samples examined, the K-m's were very similar (2.1 +/- 0.7 mu M); a value consistent with that obtained (1.2 mu M) with purified CYP2A6 in reconstituted system.5. 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.