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


CONCLUSIONS
Our results may provide useful information for the study of drug metabolism by liver microsomes in Chinese.
Shu
Y
Y
Pharmacogenetics Research Institute, Hunan Medical University, Changsha 410078, China.
Cheng
Z N
ZN
Liu
Z Q
ZQ
Wang
L S
LS
Zhu
B
B
Huang
S L
SL
Ou-Yang
D S
DS
Zhou
H H
HH
D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism; D044466:Asian People; D002681:China; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065729:Cytochrome P-450 CYP2C9; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005006:Ethnicity; D005260:Female; D006801:Humans; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D012737:Sex Factors
D003577:Cytochrome P-450 Enzyme System; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C104464:CYP3A protein, human; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human