Mizuno Y, Sone N, Saitoh T
J Neurochem. 1987 Jun;48(6):1787-93. doi: 10.1111/j.1471-4159.1987.tb05737.x.
The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and 1-methyl-4-phenylpyridinium ion (MPP+) on activities of enzyme complexes in the electron transport system were studied using isolated mitochondrial preparations from C57BL/6J mouse brains. Both MPTP and MPP+ dose-dependently inhibited activity of NADH-ubiquinone oxidoreductase (EC 1.6.5.3). The inhibition was reversible. Preincubation of freeze-thawed mitochondria with MPTP or MPP+ had no effect on the inhibition; however, when nonfrozen mitochondria were used, NADH-ubiquinone oxidoreductase activity was reduced to 46% of that in the nonincubated sample after a 5-min preincubation with MPTP and to 77% of that in the nonincubated sample after a 5-min preincubation with MPP+. Kinetic analyses revealed that inhibition of MPTP was noncompetitive and that of MPP+ uncompetitive with respect to NADH. On the other hand, inhibition of MPTP was uncompetitive and that of MPP+ noncompetitive with respect to ubiquinone. Succinate-ubiquinone oxidoreductase (complex II), dihydroubiquinone-cytochrome c oxidoreductase (complex III), and ferrocytochrome c-oxygen oxidoreductase (EC 1.9.3.1) activities were either slightly inhibited or not inhibited by MPTP or MPP+. The significance of these findings is discussed in relation to the mechanism of MPTP-induced neuronal degeneration.
使用C57BL/6J小鼠脑的分离线粒体制剂，研究了1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）和1-甲基-4-苯基吡啶离子（MPP+）对电子传递系统中酶复合物活性的影响。MPTP和MPP+均剂量依赖性地抑制NADH-泛醌氧化还原酶（EC 1.6.5.3）的活性。这种抑制是可逆的。用MPTP或MPP+对冻融线粒体进行预孵育对抑制作用没有影响；然而，当使用未冻融的线粒体时，用MPTP预孵育5分钟后，NADH-泛醌氧化还原酶活性降至未孵育样品的46%，用MPP+预孵育5分钟后，降至未孵育样品的77%。动力学分析表明，MPTP的抑制作用是非竞争性的，而MPP+对NADH的抑制作用是反竞争性的。另一方面，MPTP对泛醌的抑制作用是反竞争性的，而MPP+对泛醌的抑制作用是非竞争性的。琥珀酸-泛醌氧化还原酶（复合物II）、二氢泛醌-细胞色素c氧化还原酶（复合物III）和亚铁细胞色素c-氧氧化还原酶（EC 1.9.3.1）的活性受到MPTP或MPP+的轻微抑制或未受抑制。结合MPTP诱导神经元变性的机制对这些发现的意义进行了讨论。
