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单胺氧化酶及相关胺氧化酶作为外源性物质代谢中的I相酶。

Monoamine oxidases and related amine oxidases as phase I enzymes in the metabolism of xenobiotics.

作者信息

Strolin Benedetti M, Tipton K F

机构信息

Department of Preclinical Development and Human Pharmacology, Zambon Group, Bresso, Italy.

出版信息

J Neural Transm Suppl. 1998;52:149-71. doi: 10.1007/978-3-7091-6499-0_16.

Abstract

To date most of the interest in oxidative metabolism of xenobiotics has been devoted to the role of the microsomal cytochrome P-450 system and to establish the basis for classifying and naming P450 enzymes. The contribution of amine oxidases to the metabolism of xenobiotics has been largely neglected, with the exception of the contribution of monoamine oxidases (MAOs) to the metabolism of exogenous tyramine and the studies of the "cheese effect" produced as the result of ingestion of large amounts of tyramine-containing foods under particular conditions. A review of the involvement of the mitochondrial MAOs in drug metabolism was published in 1988. Since that time, considerable additional evidence has appeared in the literature to support the contribution of MAOs to drug metabolism. In addition, the involvement of other amine oxidases in the metabolism of foreign compounds has been established. A second review on the contribution of amine oxidases to the metabolism of xenobiotics was therefore published in 1994. On an arbitrary basis, the heterogeneous class of amine oxidases can be divided into two types according to their prosthetic group: the flavineadenine dinucleotide (FAD)-dependent amine oxidases (Monoamine Oxidase and Polyamine Oxidase) and the amine oxidases not containing FAD (Semicarbazide-sensitive amine oxidases). In this overview, the contributions of these two types in xenobiotic metabolism are considered separately.

摘要

迄今为止,对外源化合物氧化代谢的大部分研究都集中在微粒体细胞色素P - 450系统的作用上,并致力于为P450酶的分类和命名奠定基础。胺氧化酶对外源化合物代谢的贡献在很大程度上被忽视了,单胺氧化酶(MAOs)对外源性酪胺代谢的贡献以及在特定条件下摄入大量含酪胺食物所产生的“奶酪效应”的研究除外。1988年发表了一篇关于线粒体MAOs参与药物代谢的综述。从那时起,文献中出现了大量额外的证据来支持MAOs对药物代谢的贡献。此外,其他胺氧化酶对外源化合物代谢的参与也已得到证实。因此,1994年发表了第二篇关于胺氧化酶对外源化合物代谢贡献的综述。根据其辅基,胺氧化酶这一异类可任意分为两类:黄素腺嘌呤二核苷酸(FAD)依赖性胺氧化酶(单胺氧化酶和多胺氧化酶)和不含FAD的胺氧化酶(氨基脲敏感胺氧化酶)。在本综述中,将分别考虑这两类在异源物质代谢中的贡献。

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