Substrate-specificity of mammalian tissue-bound semicarbazide-sensitive amine oxidase.
Although the existence of a membrane-bound (probably plasmalemmal) semicarbazide-sensitive amine oxidase (SSAO) is well established in various mammalian tissues, and especially within vascular smooth muscle, its importance and the possible consequences of its metabolism of certain physiological and xenobiotic amines in vivo are under continuing investigation. In this respect, there are major species-related differences in substrate specificity determined in vitro, not only towards the synthetic amine benzylamine, but also towards some other aromatic amines (e.g. tyramine, tryptamine, 2-phenylethylamine, dopamine, histamine) which are possible endogenous substrates. Inhibition of SSAO can potentiate the pharmacological activity of some amines in isolated tissue (e.g. blood vessel) preparations from some species. Recent evidence has accumulated that SSAO may also be involved in metabolizing endogenous aliphatic amines such as methylamine and aminoacetone, focussing attention on the fact that the aldehyde products (formaldehyde and methylglyoxal, respectively) are potentially cytotoxic agents. Indeed, SSAO has been implicated in experimental models of cardiovascular toxicity involving conversion of the industrial aliphatic amine allylamine to acrolein. In summary, metabolism by SSAO may reduce the physiological/pharmacological effects of some amines, but the resulting metabolites (aldehydes, H2O2) may also have important actions.
Lyles
G A
GA
Department of Pharmacology and Clinical Pharmacology, University of Dundee, Ninewells Hospital and Medical School, UK.
D006631:Amine Oxidase (Copper-Containing); D000818:Animals; D001596:Benzylamines / Q000493:pharmacokinetics; D001667:Binding, Competitive; D006801:Humans; D007700:Kinetics; D008995:Monoamine Oxidase / Q000378:metabolism*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism*; D012663:Semicarbazides / Q000378:metabolism*; D013379:Substrate Specificity
D001596:Benzylamines; D012663:Semicarbazides; D006631:Amine Oxidase (Copper-Containing); D008995:Monoamine Oxidase; D000587:Oxidoreductases Acting on CH-NH Group Donors