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首页> 外文期刊>Pharmacogenetics and genomics >Functional characterization of 26 CYP2B6 allelic variants (CYP2B6.2-CYP2B6.28, except CYP2B6.22).
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Functional characterization of 26 CYP2B6 allelic variants (CYP2B6.2-CYP2B6.28, except CYP2B6.22).

机译：26个CYP2B6等位基因变体（CYP2B6.2-CYP2B6.28，CYP2B6.22除外）的功能表征。

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摘要

Cytochrome P450 2B6 (CYP2B6) is a potentially important enzyme for the metabolism of clinical drugs, and it exhibits genetic polymorphism. Thus far, 29 allelic variants of CYP2B6 (CYP2B6*1-CYP2B6*29) have been identified. This study aimed to investigate whether 26 of the variant alleles of CYP2B6 (CYP2B6*2-CYP2B6*21 and CYP2B6*23-CYP2B6*28) affect its kinetics in the metabolism of 7-ethoxy-4-trifluoromethylcoumarin (7-EFC) and selegiline. Wild-type CYP2B6.1 and the allelic variants were heterologously expressed in COS-7 cells. In-vitro kinetic analysis revealed that when compared with the wild-type protein CYP2B6.1, CYP2B6.10 and CYP2B6.14 exhibited significantly lower V(max)/K(m) values for selegiline N-demethylation. The kinetic parameters of CYP2B6.8, CYP2B6.11, CYP2B6.12, CYP2B6.13, CYP2B6.15, CYP2B6.18, CYP2B6.21, CYP2B6.24, and CYP2B6.28 could not be determined because these enzymes were inactive in the deethylation of 7-EFC and the N-demethylation/N-depropagylation of selegiline. These findings provide useful information for further genotype-phenotype studies on interindividual differences in the metabolism of CYP2B6 substrate drugs.
机译：细胞色素P450 2B6（CYP2B6）是临床药物代谢中潜在的重要酶，并且具有遗传多态性。迄今为止，已经鉴定出29种CYP2B6等位基因变体（CYP2B6 * 1-CYP2B6 * 29）。这项研究旨在调查CYP2B6变异等位基因（CYP2B6 * 2-CYP2B6 * 21和CYP2B6 * 23-CYP2B6 * 28）中的26个是否影响其在7-乙氧基-4-三氟甲基香豆素（7-EFC）代谢中的动力学司来吉兰。野生型CYP2B6.1和等位基因变体在COS-7细胞中异源表达。体外动力学分析显示，与野生型蛋白CYP2B6.1相比，CYP2B6.10和CYP2B6.14对司来吉兰N-去甲基化的V（max）/ K（m）值显着降低。无法确定CYP2B6.8，CYP2B6.11，CYP2B6.12，CYP2B6.13，CYP2B6.15，CYP2B6.18，CYP2B6.21，CYP2B6.24和CYP2B6.28的动力学参数，因为这些酶在7-EFC的去乙基化和司来吉兰的N-去甲基化/ N-去丙基化。这些发现为CYP2B6底物药物代谢个体间差异的进一步基因型-表型研究提供了有用的信息。

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