抑制单克隆抗体对人体细胞色素P450 1 a2:分析非那西汀O-deethylation在人类肝脏。

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杨TJ, Sai Y, Krausz千瓦,冈萨雷斯FJ, Gelboin高压

抑制单克隆抗体对人体细胞色素P450 1 a2:分析非那西汀O-deethylation在人类肝脏。

药物基因学。1998年10月,8 (5):375 - 82。

PubMed ID

9825829 (在PubMed

]

文摘

人类细胞色素P450 1 a2代谢大量常用的药物和从事致癌物代谢和激活。Baculovirus-expressed 1 a2用于免疫小鼠产生杂种细胞产生单克隆抗体(mab)。三个2050年克隆化验了马伯,MAb 26-7-5, MAb 951-5-1, MAb 1812-2-4,具体为评估1 a2的酶联免疫吸附试验和免疫印迹。非那西汀的三个马伯抑制1 a2-catalysed新陈代谢,7-ethoxycoumarin chlorzoxazone和菲85%以上。马伯是非常具体的1 a2和没有抑制其他11个人类p450酶类。的phenancetin O-deethylation活动变化从0.44 - -2.49 nmol /分钟/ nmol在八人肝微粒体P450样本。马伯26-7-5抑制1 a2-dependent非那西汀O-deethylation这些样本的64 - 84%表明1 a2对这个反应的贡献,除了O-deethylation其他p450酶类的作用。独立分析重组人类p450显示1 a1, a2, a6和2 c19表现出非那西汀O-deethylation活动,1 a1和a2是最活跃的2 c19和2 a6紧随其后。八其他p450活性对非那西汀O-deethylation。不同的角色P450在八与特定的个体抑制马伯肝脏样本进行了分析。 Inhibitory antibodies to 1A2, 2C8/9/18/19, 2A6, 2D6, 2E1, and 1A1 were combinatorially added to the microsomes. The O-deethylation activity was inhibited by antibodies to 1A2 (64-84%), to 2C19 (4.6-20%) and to 2A6 (0-8.8%). The total activity inhibited by antibodies to P450 2E1, 2D6 and 1A1 was less than 4.5%, indicating a minor role for these P450s in phenancetin metabolism in human liver microsomes. Thus, 1A2, 2C 9 and 2A6 are the dominant P450s for phenacetin O-deethylation. These studies demonstrate the use of inhibitory MAbs to P450s for a simple and precise assessment of the quantitative role of each P450 in the metabolism of substrates, including drugs, carcinogens, mutagens, environmental chemicals and endobiotics.

DrugBank数据引用了这篇文章

药物酶

药物	酶	类	生物	药理作用	行动
Chlorzoxazone	细胞色素P450 1 a2	蛋白质	人类	未知的	底物	细节