Shu Y, Cheng Z N, Liu Z Q, Wang L S, Zhu B, Huang S L, Ou-Yang D S, Zhou H H
Pharmacogenetics Research Institute, Hunan Medical University, Changsha 410078, China.
Acta Pharmacol Sin. 2001 Mar;22(3):283-8.
To compare the level and/or activity of several important cytochrome P-450 (CYP) enzymes in liver microsomes prepared from different Chinese subjects.
Individual CYP contents, including CYP1A2, CYP2C9, and CYP3A4, in liver microsomes of 17 Han, 17 Zhuang, and 8 Miao subjects were determined by using Western blot analysis and densitometric scanning. The substrates for measuring the activity of individual CYP in vitro included phenacetin, tolbutamide, debrisoquine, and omeprazole.
There was a large interindividual variability in the content and activity of CYP1A2, 2C9 and 3A4. And the activity of CYP2D6 also varied greatly between individual samples. CYP3A4 (32 %) is the most abundant CYP in Chinese liver microsomes, and the levels of CYP2C9 (19 %) and CYP1A2 (16 %) were also considerable. No clear ethnic, sex- and age-related differences in individual CYP content and catalytic activity were detected in 42 Chinese liver samples, except that there were somewhat ethnic and sex-related differences in the content and activity of CYP1A2. Good correlation between enzyme protein content and activity was found for CYP1A2, 2C9 and 3A4.
Our results may provide useful information for the study of drug metabolism by liver microsomes in Chinese.
比较不同中国受试者制备的肝微粒体中几种重要细胞色素P-450（CYP）酶的水平和/或活性。
采用蛋白质免疫印迹分析和光密度扫描法测定17名汉族、17名壮族和8名苗族受试者肝微粒体中CYP1A2、CYP2C9和CYP3A4等个体CYP含量。体外测定个体CYP活性的底物包括非那西丁、甲苯磺丁脲、异喹胍和奥美拉唑。
CYP1A2、2C9和3A4的含量和活性存在较大个体差异。个体样本间CYP2D6活性也有很大差异。CYP3A4（32%）是中国肝微粒体中含量最丰富的CYP，CYP2C9（19%）和CYP1A2（16%）的水平也相当可观。在42份中国肝脏样本中，未检测到个体CYP含量和催化活性存在明显的种族、性别和年龄相关差异，除了CYP1A2的含量和活性存在一定的种族和性别相关差异。发现CYP1A2、2C9和3A4的酶蛋白含量与活性之间具有良好的相关性。
我们的结果可能为研究中国人肝微粒体的药物代谢提供有用信息。
