LIDOCAINE METABOLISM IN HUMAN-LIVER MICROSOMES BY CYTOCHROME-P450IIIA4
LIDOCAINE METABOLISM IN HUMAN-LIVER MICROSOMES BY CYTOCHROME-P450IIIA4
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DOI：
10.1038/clpt.1989.180
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发表时间：
1989-11-01
影响因子：
6.7
通讯作者：
MEYER, UA
中科院分区：
文献类型：
--
作者：
BARGETZI, MJ;AOYAMA, T;MEYER, UA
在 13 名肾移植捐献者和一名肝硬化患者的人肝微粒体中研究了利多卡因及其主要代谢物单乙基甘氨酸 (MEGX) 的代谢。代谢物形成的个体间差异相当大。双相动力学表明至少涉及两种不同的酶活性。通过使用一系列识别不同人类细胞色素 P450 同工酶的抗血清，我们能够将 P450III 基因家族的一种酶鉴定为两种酶之一。通过在 HepG2 细胞中表达人 P450IIIA4 互补脱氧核糖核酸 (cDNA)，我们直接证明了该 P450 同工酶的利多卡因脱乙基酶活性。这些数据表明 P450IIA4 至少部分负责微粒体 MEGX 的形成。
The metabolism of lidocaine to its major metabolite monoethylglycinexylidide (MEGX) was studied in human liver microsomes of 13 kidney transplant donors and of one patient with liver cirrhosis. Interindividual variation in metabolite formation was considerable. Biphasic kinetics indicated the involvement of at least two distinct enzymatic activities. With use of a series of antisera that recognize different human cytochrome P450 isozymes, we were able to identify an enzyme of the P450III gene family as one of two enzymes. By expressing human P450IIIA4 complementary deoxyribonucleic acid (cDNA) in HepG2 cells, we directly demonstrated lidocaine-deethylase activity for this P450 isozyme. These data suggest that P450IIA4 is at least in part responsible for microsomal MEGX formation.