Properties of a Semicarbazide-Sensitive Amine Oxidase in Human Umbilical Artery

Abstract

The metabolism of some aromatic amines by amine oxidase activities in human umbilical artery homogenates has been studied. The inhibitory effects of clorgyline showed that 5-hydroxytryptamine (5-HT) and tryptamine, 1 mM, were predominantly substrates for monoamine oxidase (MAO) type A, whereas MAO-A and B were both involved in the metabolism of beta-phenylethylamine (PEA), 100 microM, and tyramine, 1 mM. About 20-30% of tyramine and PEA metabolism was resistant to 1 mM clorgyline, but sensitive to inhibition by semicarbazide, 1 mM, indicating the presence of a semicarbazide-sensitive amine oxidase (SSAO). Benzylamine, 1 mM, appeared to be metabolized exclusively by SSAO with a Km (161 microM) at pH 7.8 similar to that found for SSAO in other human tissues. Tyramine and PEA were relatively poor substrates for SSAO, with very high apparent Km values of 17.6 and 13.3 mM, respectively, when determined in the presence of clorgyline, 10(-3) M, added to inhibit any metabolism of those amines by MAO activities. However, kinetic studies with benzylamine indicated that clorgyline, 10(-3) M, also appears to inhibit SSAO competitively such that the true Km values for tyramine and PEA may be about 60% of those apparent values given above. No evidence for the metabolism of 5-HT or tryptamine by SSAO was obtained. The aliphatic amine methylamine was recently shown to be a specific substrate for SSAO in umbilical artery homogenates. We have used benzylamine and methylamine as SSAO substrates in histochemical studies to localize SSAO in tissue sections.(ABSTRACT TRUNCATED AT 250 WORDS)

The influence of amine metabolizing enzymes on the pharmacology of tyramine in the isolated perfused mesenteric arterial bed of the rat

“…Nevertheless, in rat in vitro models where MAO inhibitors are tested for their ability to potentiate the actions of Tyr, the influence of SSAO should be considered when interpreting the results. It should also be noted that, although human blood vessels possess a similar SSAO activity (Lewinsohn, 1981), it has a very low affinity for Tyr (Precious & Lyles, 1988). Thus it would be unwise to suggest, from experiments of this nature, that inhibition of SSAO in the human subject, is involved in the 'cheese reaction' (Blackwell, 1963).…”

Tissue Activity and Cellular Localization of Human Semicarbazide-sensitive Amine Oxidase

“…Tissue-bound SSAO has been described in many mammalian tissues, especially in those that are highly vascularized (Lyles 1996), and blood vessels (Precious and Lyles 1988). SSAO activity has also been found in nonvascular tissues, such as adipocytes (Barrand et al 1984;Morris et al 1997), odontoblasts (Norqvist et al 1981), and different parts of the bovine eye (Fernández de Arriba et al 1991) (see Lyles 1996 for review).…”

A heretofore undisclosed crux of Eosinophilia-Myalgia Syndrome: compromised histamine degradation

“…In humans, plasma/serum 'MAO' 21 is a poor and negligible oxidant of histamine and serotonin, respectively [129,131], unlike the corresponding enzymes in other species. Serotonin has been a poor substrate if not inhibitor of the human SSAO isoenzymes that have been examined thus far [129,[131][132][133][134]. Depending on the reaction conditions of the isoenzyme as well as the species examined, tryptamine can be a substrate [135][136][137][138] and inhibitor [139,140] of SSAO; according to most [127,133,134,137,138,141,142] but not all reports [129,143,144], tryptamine is a poor substrate for the human isoenzymes of SSAO studied to date.…”