Naoi M, Nagatsu T
Department of Biochemistry, Nagoya University School of Medicine, Japan.
J Neurochem. 1988 Apr;50(4):1105-10. doi: 10.1111/j.1471-4159.1988.tb10579.x.
A series of methylquinolines (MQ) were found to inhibit markedly type A monoamine oxidase (MAO) in human brain synaptosomal mitochondria. 4-MQ and 6-MQ inhibited type A MAO (MAO-A) competitively and 7- and 8-MQ inhibited MAO-A noncompetitively. Among these four isomers of MQ, 6-MQ was the most potent inhibitor; the Ki value toward MAO-A was 23.4 +/- 1.8 microM, which was smaller than the Km value toward kynuramine, an amine substrate, 46.2 +/- 2.8 microM. On the other hand, MQ were very weak inhibitors of type B MAO (MAO-B) and 8-MQ did not inhibit MAO-B in brain synaptosomal mitochondria. The inhibition of MAO-A proved to be reversible; by dialysis the inhibition of MQ was completely reversible. The affinity of these isomers of MQ toward MAO-A or -B was confirmed further with human liver mitochondria as sources of MAO-A and -B and with human placental mitochondria and rat pheochromocytoma PC12h cell line as sources of MAO-A. The relationship of the chemical structure of structurally related quinoline and isoquinoline derivatives to inhibition of the activity of type A or B MAO was examined.
人们发现一系列甲基喹啉（MQ）能显著抑制人脑海突触体线粒体中的A型单胺氧化酶（MAO）。4-MQ和6-MQ竞争性抑制A型MAO（MAO-A），而7-MQ和8-MQ非竞争性抑制MAO-A。在MQ的这四种异构体中，6-MQ是最有效的抑制剂；其对MAO-A的Ki值为23.4±1.8微摩尔，小于对胺底物犬尿胺的Km值46.2±2.8微摩尔。另一方面，MQ是B型MAO（MAO-B）的非常弱的抑制剂，8-MQ在脑突触体线粒体中不抑制MAO-B。MAO-A的抑制作用被证明是可逆的；通过透析，MQ的抑制作用完全可逆。以人肝线粒体作为MAO-A和MAO-B的来源，以及以人胎盘线粒体和大鼠嗜铬细胞瘤PC12h细胞系作为MAO-A的来源，进一步证实了这些MQ异构体对MAO-A或MAO-B的亲和力。研究了结构相关的喹啉和异喹啉衍生物的化学结构与A型或B型MAO活性抑制之间的关系。
