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Interindividual variations in levels and activities of cytochrome P-450 in liver microsomes of Chinese subjects.

Y Shu, Zeneng Cheng, Zhaoqian Liu, L S Wang, Bing Zhu, Song‐Lin Huang, Dongsheng Ouyang, Hong-Hao Zhou

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Abstract

AIM: To compare the level and/or activity of several important cytochrome P-450 (CYP) enzymes in liver microsomes prepared from different Chinese subjects. METHODS: 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. RESULTS: 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. CONCLUSION: Our results may provide useful information for the study of drug metabolism by liver microsomes in Chinese.

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What this paper is about

AIM: To compare the level and/or activity of several important cytochrome P-450 (CYP) enzymes in liver microsomes prepared from different Chinese subjects. METHODS: 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. RESULTS: 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. CONCLUSION: Our results may provide useful information for the study of drug metabolism by liver microsomes in Chinese.

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Available abstract

AIM: To compare the level and/or activity of several important cytochrome P-450 (CYP) enzymes in liver microsomes prepared from different Chinese subjects. METHODS: 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. RESULTS: 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. CONCLUSION: Our results may provide useful information for the study of drug metabolism by liver microsomes in Chinese.

Key concepts: CYP1A2, Microsome, Tolbutamide, Cytochrome P450, Phenacetin, CYP3A4, Debrisoquine, CYP2D6

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