Mammalian plasma and tissue-bound semicarba ide-sensitive amine oxidases: Biochemical, pharmacological and toxicological aspects

Abstract

Mammalian plasma and tissues contain various soluble and membrane-bound enzymes which metabolize the synthetic amine benzylamine particularly well. The sensitivity of these enzymes to inhibition by semicarbazide and related compounds suggests That they contain a cofactor with a reactive carbonyl group, which has been proposed to be either pyridoxal phosphate, pyrrologuineline gninone or (more recently) 6-hydroxydopa. It is not yet clear ff all of these semicarbazide-sensitive amine oxidases (SSAOs) are coppery enzymes. A variety of compounds have now been identified as relatively selective inhibitors to distinguish the SSAOS from other amine oxidases, in order to investigate the properties of SSAOs and their potential role in biogenic and xenobiotic amine metabolism in vivo. While -plea SSAO is soluble, most tissue SSAOs appear to be membrane-bound, probably plasmalemmal enzymes, which may be capable of metabolizing extracellular amines. Vascular (and non-vascular) smooth muscle cells have particularly high SSAO activity, although recently the enzyme has been found in other cell types (e.g. adipocytes, chondrocytes, odontoblasts) implying a functional importance not restricted solely to smooth muscle. The substrate specificity of plasma and tissue SSAOs shows considerable species-related variations. For example, while some y-occurring aromatic amines such as tyramine and tryptamine are metabolized well by SSAO in homagenates of rat blood vessels, and also in vitro inhibition of SSAO can potentiate vasoconstrictor actions of these ammes in rat vascular preparations, these amiss are poor substrates for human SSAO, tip complicating attempts to generalize possible physiological roles for these enzymes. Vascular SSAO can metabolize the xembiotic aliphatic amine, anybunine, to the cytotoxic aldehyde acrolem and this has been linked to the ability of aliylambe administration to produce cardiovascular lesions in experimental animals, sometimes mimidking features of atherosclerotic disease. Recent studies showing that the endogenously-occurring amines methylamine and aminoacetone are metabolized in vitro to formaldehyde and maeltylglyoxal, respectively, by SSAO in some animal (including human) tissues, suggest the possibility that toxicological consequences upon cellular function could result if such conversions occur in vivo.