Precious E, Lyles G A
Department of Pharmacology and Clinical Pharmacology, University of Dundee, Ninewells Hospital, UK.
J Pharm Pharmacol. 1988 Sep;40(9):627-33. doi: 10.1111/j.2042-7158.1988.tb05322.x.
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)
已对人脐动脉匀浆中胺氧化酶活性对某些芳香胺的代谢进行了研究。氯吉兰的抑制作用表明，1 mM的5-羟色胺（5-HT）和色胺主要是A型单胺氧化酶（MAO）的底物，而MAO-A和B都参与了100 μM的β-苯乙胺（PEA）和1 mM的酪胺的代谢。约20%-30%的酪胺和PEA代谢对1 mM氯吉兰有抗性，但对1 mM氨基脲的抑制敏感，表明存在氨基脲敏感胺氧化酶（SSAO）。1 mM的苄胺似乎仅由SSAO代谢，在pH 7.8时其Km（161 μM）与在其他人体组织中发现的SSAO的Km相似。当在存在10⁻³ M氯吉兰以抑制MAO活性对这些胺的任何代谢的情况下测定时，酪胺和PEA是SSAO相对较差的底物，其表观Km值分别非常高，为17.6和13.3 mM。然而，用苄胺进行的动力学研究表明，10⁻³ M的氯吉兰似乎也竞争性抑制SSAO，使得酪胺和PEA的真实Km值可能约为上述表观值的60%。未获得SSAO代谢5-HT或色胺的证据。脂肪族胺甲胺最近被证明是脐动脉匀浆中SSAO的特异性底物。我们在组织化学研究中使用苄胺和甲胺作为SSAO底物来在组织切片中定位SSAO。（摘要截短于250字）
