Mammalian plasma and tissue-bound semicarbazide-sensitive amine oxidases: biochemical, pharmacological and toxicological aspects.

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