Inhibition of type A monoamine oxidase by 1-methyl-4-phenylpyridine.
1-Methyl-4-phenylpyridine (MPP+) is now confirmed to be one of the oxidative products of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) by type B monoamine oxidase (MAO-B) and is considered to cause a parkinsonism-like syndrome. We studied the effect of MPP+ on type A monoamine oxidase (MAO-A) activity in mitochondria prepared from various sources. By kinetic analysis, MPP+ was found to inhibit MAO-A in competition with the substrate, kynuramine. The Ki value of MAO-A with MPP+ in human brain synaptosomal mitochondria (1.3 microM) was much lower than the Ki values of MAO-A in other organs. Among the MAO-A samples, MAO-A in intrasynaptosomal mitochondria from human brain was the most sensitive to MPP+. The Ki value of MAO-A with MPP+ in striatum (1.6 microM and 2.0 microM for MAO-A prepared from putamen and from caudate) was similar to the Ki value of MAO-A in synaptosomes from cortex. The difference in the Ki values of MPP+ for MAO-A from various sources was considered to be due to the difference in lipid components of mitochondria. The possible significance of the inhibition of MAO-A was discussed in terms of the etiology of parkinsonism.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D015655:1-Methyl-4-phenylpyridinium; D001921:Brain / Q000201:enzymology; D006801:Humans; D007700:Kinetics; D008928:Mitochondria / Q000201:enzymology*; D008930:Mitochondria, Liver / Q000201:enzymology; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010920:Placenta / Q000201:enzymology; D011725:Pyridines / Q000494:pharmacology; D011726:Pyridinium Compounds / Q000494:pharmacology*; D013347:Subcellular Fractions / Q000201:enzymology
D008996:Monoamine Oxidase Inhibitors; D011725:Pyridines; D011726:Pyridinium Compounds; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D008995:Monoamine Oxidase; D015655:1-Methyl-4-phenylpyridinium