Largeron M
UMR 8638, CNRS-université Paris Descartes, synthèse et structure de molécules d'intérêt pharmacologique, faculté des sciences pharmaceutiques et biologiques, 4, avenue de l'Observatoire, 75270 Paris cedex 06, France.
Ann Pharm Fr. 2011 Jan;69(1):53-61. doi: 10.1016/j.pharma.2010.10.002. Epub 2010 Dec 28.
Copper amine oxidases (CuAOs) are ubiquitous enzymes, which play a vital role in the physiology and pathology of mammals in controlling the metabolism of various primary monoamines, diamines and polyamines of endogenous or xenobiotic origin. CuAOs, which belong to the quinoproteins family, possess two cofactors: tightly bound Cu(II) and a quinone residue, which catalyzes the oxidative deamination of primary amines with concomitant production of aldehyde, ammonia and hydrogen peroxide through a "ping-pong" mechanism. Interest in human enzymes of the CuAOs class has increased in recent years driven by the discovery that the human vascular adhesion protein-1 (VAP-1), which regulates leucocyte trafficking and glucose transport, is a CuAO enzyme. The activities of CuAOs are increased in various human disorders such as diabetes, Alzheimer's disease and many inflammation-associated diseases leading to the overproduction of toxic metabolites, especially hydrogen peroxide and aldehyde compounds. As most consequences are pathological, effective and selective inhibitors of CuAOs should be of great interest as therapeutic agents. Nevertheless, the utilization of CuAOs to generate enzymatic toxic products into cancer cells for selective in situ killing, deserves to be considered in cancer therapy. This paper briefly highlights recent progress in the study of physiological, pathological and molecular aspects of CuAOs in mammals. Furthermore, a small molecule, that mimics the metabolic activity of CuAOs toward endogenous and exogenous amines, is described because it could be used as a surrogate of enzymes for a preliminary screening of potential inhibitors of CuAO enzymes.
铜胺氧化酶（CuAOs）是广泛存在的酶，在哺乳动物的生理和病理过程中，对于控制内源性或外源性来源的各种一级单胺、二胺和多胺的代谢起着至关重要的作用。属于醌蛋白家族的CuAOs拥有两种辅因子：紧密结合的Cu(II)和一个醌残基，其通过“乒乓”机制催化一级胺的氧化脱氨反应，同时产生醛、氨和过氧化氢。近年来，由于发现调节白细胞运输和葡萄糖转运的人类血管粘附蛋白-1（VAP-1）是一种CuAO酶，人们对这类人类酶的兴趣有所增加。在各种人类疾病中，如糖尿病、阿尔茨海默病和许多炎症相关疾病，CuAOs的活性会增加，导致有毒代谢产物，特别是过氧化氢和醛类化合物的过量产生。由于大多数后果是病理性的，CuAOs的有效和选择性抑制剂作为治疗药物应该会引起极大的兴趣。然而，利用CuAOs在癌细胞中产生酶促有毒产物以进行选择性原位杀伤，在癌症治疗中值得考虑。本文简要介绍了哺乳动物CuAOs在生理、病理和分子方面研究的最新进展。此外，还描述了一种小分子，它模拟CuAOs对内源性和外源性胺的代谢活性，因为它可以用作酶的替代物，用于初步筛选CuAO酶的潜在抑制剂。
