Properties of a semicarbazide-sensitive amine oxidase in human umbilical artery.
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)
Precious
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Department of Pharmacology and Clinical Pharmacology, University of Dundee, Ninewells Hospital, UK.
Lyles
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D003010:Clorgyline / Q000494:pharmacology; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000033:anatomy & histology / Q000201:enzymology*; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism*; D010627:Phenethylamines / Q000494:pharmacology; D012663:Semicarbazides / Q000494:pharmacology*; D012701:Serotonin / Q000494:pharmacology; D014363:Tryptamines / Q000494:pharmacology; D014439:Tyramine / Q000494:pharmacology; D014469:Umbilical Arteries / Q000033:anatomy & histology / Q000201:enzymology
D010627:Phenethylamines; D012663:Semicarbazides; D014363:Tryptamines; D012701:Serotonin; D000587:Oxidoreductases Acting on CH-NH Group Donors; D003010:Clorgyline; D014439:Tyramine