title: Amine oxidases of the quinoproteins family: their implication in the metabolic oxidation of xenobiotics.
abstract: 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.
authors.affiliation: 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. martine.largeron@parisdescartes.fr
authors.forename: M
authors.initials: M
authors.lastname: Largeron
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology; D006631:Amine Oxidase (Copper-Containing) / Q000378:metabolism*; D000588:Amines / Q000378:metabolism; D000818:Animals; D002384:Catalysis; D003920:Diabetes Mellitus / Q000201:enzymology; D006801:Humans; D007249:Inflammation / Q000201:enzymology; D008322:Mammals / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology; D010084:Oxidation-Reduction; D054852:Small Molecule Libraries; D009626:Terminology as Topic; D015262:Xenobiotics / Q000378:metabolism*
chemical_list: D000588:Amines; D054852:Small Molecule Libraries; D015262:Xenobiotics; D006631:Amine Oxidase (Copper-Containing)