Nicklas W J, Vyas I, Heikkila R E
Life Sci. 1985 Jul 1;36(26):2503-8. doi: 10.1016/0024-3205(85)90146-8.
1-methyl-4-phenylpyridine (MPP+), a major metabolite of the neurotoxin, 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP) inhibited the ADP-stimulated and uncoupled oxidation of NADH-linked substrates by brain mitochondrial preparations. MPTP itself was ineffective. The apparent Ki's for MPP+ inhibition of pyruvate or glutamate oxidation by purified rat brain mitochondria were approximately 300 and 400 microM, respectively; with mouse brain mitochondria the values were lower, 60 and 150 microM, respectively. Succinate oxidation was unaffected by either compound. Compromise of mitochondrial oxidative capacity by MPP+ could be an important factor in mechanisms underlying the toxicity of MPTP.
1-甲基-4-苯基吡啶（MPP+）是神经毒素1-甲基-4-苯基-1,2,5,6-四氢吡啶（MPTP）的主要代谢产物，它能抑制脑线粒体制剂对ADP刺激的以及未偶联的NADH相关底物的氧化作用。MPTP本身则无此作用。纯化的大鼠脑线粒体中，MPP+抑制丙酮酸或谷氨酸氧化的表观抑制常数（Ki）分别约为300和400微摩尔；小鼠脑线粒体的相应值较低，分别为60和150微摩尔。琥珀酸氧化不受这两种化合物的影响。MPP+对线粒体氧化能力的损害可能是MPTP毒性机制中的一个重要因素。
