Oxidation of analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by monoamine oxidases A and B and the inhibition of monoamine oxidases by the oxidation products.
Oxidation of analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine by monoamine oxidases A and B and the inhibition of monoamine oxidases by the oxidation products.
复制标题
单胺氧化酶 A 和 B 氧化 1-甲基-4-苯基-1,2,3,6-四氢吡啶类似物以及氧化产物对单胺氧化酶的抑制作用。
DOI：
10.1111/j.1471-4159.1989.tb09250.x
复制
发表时间：
1989
影响因子：
4.7
通讯作者：
Singer,TP
中科院分区：
文献类型：
--
作者：
Youngster,SK;McKeown,KA;Jin,YZ;Ramsay,RR;Heikkila,RE;Singer,TP
用人胎盘单胺氧化酶-A(MAO-A)和牛肝单胺氧化酶-B(MAO-B)测定了20个ofl‐methyl‐4‐phenyl‐l，2，3，6‐tet‐rahydropyridine类似物的氧化能力。几个MPTP类似物对MAO-A、MAO-B或两者都是非常好的底物，并且具有低Km值和高周转数。这些值分别与MAO-A和MAO-B的良好底物犬尿胺和苯丙胺相近甚至更好。MPTP被MAO-A和MAO-B氧化的Km值相对较低。相反，MAO-B氧化MPTP的周转次数明显高于MAO-A的Km值。相应的MPTP和几种MPTP类似物在微摩尔浓度下与Ki值竞争抑制MAO-A；相反，在相当高的浓度下(即100μ/KI值)，吡啶类物种竞争抑制MAO-B。这些数据提供了有关MAO-A和MAO-B氧化四氢吡啶的结构要求以及吡啶类化合物对这些酶的抑制作用的信息
Twenty analogs ofl‐methyl‐4‐phenyl‐l,2,3,6‐tet‐rahydropyridine (MPTP) were tested for their capacity to be xidized by pure monoamine oxidase‐A (MAO‐A) prepared from human placenta and pure monoamine oxidase‐B (MAO‐B) prepared from beef liver. Several of the MPTP analogs were very good substrates for MAO‐A, for MAO‐B, or for both and had lowKmvalues and high turnover numbers. These values were similar to or even better than those of kynuramine and benzylamine, good substrates for MAO‐A and MAO‐B, respectively. MPTP had relatively lowKmvalues for oxidation by both MAO‐A and MAO‐B. In contrast, the turnover number for MPTP oxidation by MAO‐B was considerably higher than the value for MAO‐A. The corresponding pyridinium species of MPTP and several of the MPTP analogs inhibited MAO‐A competitively withKivalues at micromolar concentrations; in contrast the pyridinium species inhibited MAO‐B competitively at considerably higher concentrations (i.e., 100 μMor greaterKivalues). The data provide information concerning the structural requirements for the oxidation of tetrahydropyridines by MAO‐A and MAO‐B and the inhibition of these enzymes by pyridini‐ums