识别变异的CYP3A4代谢和表征能力睾丸激素和毒死蜱。
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戴D,唐J,玫瑰R,霍奇森E,恩斯托克RJ, Mohrenweiser HW,戈尔茨坦农协
识别变异的CYP3A4代谢和表征能力睾丸激素和毒死蜱。
J Exp其他杂志》2001年12月,299(3):825 - 31所示。
- PubMed ID
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11714865 (在PubMed]
- 文摘
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CYP3A4是最丰富的细胞色素P450 (CYP)在同种型成人肝脏。它代谢许多临床、生理和毒物学地重要的化合物。CYP3A4 40倍不同的表达在人类肝脏、个人和CYP3A4代谢基质不同体内至少10倍。单核苷酸多态性(SNPs) CYP3A4被确定的基因组DNA直接测序72人从三个不同的民族,包括白人、黑人(非洲裔和非洲俾格米人),和亚洲人。共有28个snp,包括五个生产编码变更M445T (CYP3A4 * 3), R162Q (CYP3A4 * 15), F189S (CYP3A4 * 17), L293P (CYP3A4 * 18),和P467S (CYP3A4 * 19)。后者四个代表新alleic变体。种族差异观察单个snp的频率。CYP3A R162Q被发现只有在黑人人口4%的等位基因频率。CYP3A4 F189S和CYP3A4 M445T被确定在白种人等位基因频率为2%和4%,分别。L293P和P467S只是观察到2%的亚洲人在等位基因的频率。 The cDNAs for the F189S, L293P, M445T, and P467S mutant alleles were constructed by site-directed mutagenesis and expressed in an Escherichia coli expression system. Testosterone and the insecticide chlorpyrifos were used to assess the catalytic activities of the most common CYP3A4 allele (CYP3A4*1) and its allelic variants. CYP3A4 F189S exhibited lower turnover numbers for testosterone and chlorpyrifos, while CYP3A4 L293P had higher turnover numbers for both substrates. The turnover numbers of the CYP3A4 M445T and P467S alleles to metabolize these compounds were not significantly different from those of wild-type CYP3A4.