@article {Cashman163, author = {J R Cashman and D M Ziegler}, title = {Contribution of N-oxygenation to the metabolism of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) by various liver preparations.}, volume = {29}, number = {2}, pages = {163--167}, year = {1986}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, abstract = {Liver microsomes from uninduced mice and rats catalyze NADPH- and oxygen-dependent N-oxygenation of the neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine). The N-oxide is the principal product and accounts for 95-96\% of the total MPTP metabolized by microsomes. Demethylation of MPTP is detectable but the rate of nor-MPTP formation was never more than 4-6\% of the rate of N-oxygenation. Studies on the biochemical mechanisms for N-oxygenation of MPTP suggest that this reaction is catalyzed exclusively by the flavin-containing monooxygenase. This conclusion is based on the effects of selective cytochrome P-450 inhibitors, positive effectors, and alternate substrates for the flavin-containing monooxygenase as well as on studies with the purified hog liver enzyme. MPTP is an excellent substrate for this monooxygenase with a Km of 30-33 microM. Limited studies with human liver whole homogenates suggest that N-oxygenation is also a major route for the metabolism of MPTP in man and the rate of N-oxide formation is approximately equal to the rate of mitochondrial monoamine oxidase-dependent MPDP+ (1-methyl-4-phenyl-2,3-dihydropyridinium species) production.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/29/2/163}, eprint = {https://molpharm.aspetjournals.org/content/29/2/163.full.pdf}, journal = {Molecular Pharmacology} }