Oxidation and enzyme-activated irreversible inhibition of rat liver monoamine oxidase-B by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP).
The compound 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which produces symptoms resembling Parkinson's disease in humans, acts both as a substrate and an enzyme-activated irreversible inhibitor of the B-form of monoamine oxidase from rat liver. Analysis of the inhibitory process showed the compound to be considerably more efficient as a substrate than as an irreversible inhibitor, with about 17000 mol of product being formed per mol of enzyme inactivated. The half-time of the inhibitory process was about 22 min. With the A-form of the enzyme, the compound had a lower Km value and a considerably lower maximum velocity than the corresponding values obtained with the B-form. Under the conditions used in the present work the inhibition of the A-form of the enzyme was largely reversible.
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000818:Animals; D003010:Clorgyline / Q000494:pharmacology; D005260:Female; D006207:Half-Life; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D007700:Kinetics; D008930:Mitochondria, Liver / Q000201:enzymology*; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010627:Phenethylamines / Q000378:metabolism; D010920:Placenta / Q000201:enzymology; D011247:Pregnancy; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D012642:Selegiline / Q000494:pharmacology; D012701:Serotonin / Q000378:metabolism
D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D010627:Phenethylamines; D011725:Pyridines; D012642:Selegiline; C029261:phenethylamine; D012701:Serotonin; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D003010:Clorgyline