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• W2148462089 abstract "Metabolic enzymes are involved in the activation/deactivation of the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyiridine (MPTP) neurotoxin and its naturally occurring analogs 2-methyltetrahydro- β -carbolines. The metabolic profile and biotransformation of these protoxins by three enzymes, monoamine oxidase (MAO), cytochrome P450, and heme peroxidases (myeloperoxidase and lactoperoxidase), were investigated and compared. The metabolite profile differed among the enzymes investigated. MAO and heme peroxidases activated these substances to toxic pyridinium and β -carbolinium species. MAO catalyzed the oxidation of MPTP to 1-methyl-4-phenyl-2,3-dihydropyridinium cation (MPDP + ), whereas heme peroxidases catalyzed the oxidation of MPDP + to 1-methyl-4-phenylpyridinium (MPP + ) and of 2-methyltetrahydro- β -carboline to 2-methyl-3,4-dihydro- β -carbolinium cation (2-Me-3,4-DH β C + ). These substances were inactivated by cytochrome P450 2D6 through N -demethylation and aromatic hydroxylation (MPTP) and aromatic hydroxylation (2-methyltetrahydro- β -carboline). In conclusion, the toxicological effects of these protoxins might result from a balance between the rate of their activation to toxic products (i.e., N -methylpyridinium-MPP + and MPDP + - and N -methyl- β -carbolinium— β C + —) by MAO and heme peroxidases and the rate of inactivation (i.e., N -demethylation, aromatic hydroxylation) by cytochrome P450 2D6." @default.
• W2148462089 created "2016-06-24" @default.
• W2148462089 creator A5023409251 @default.
• W2148462089 creator A5036730297 @default.
• W2148462089 creator A5079009975 @default.
• W2148462089 date "2013-01-01" @default.
• W2148462089 modified "2023-10-18" @default.
• W2148462089 title "Metabolite Profile Resulting from the Activation/Inactivation of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 2-Methyltetrahydro-<b><i>β</i></b>-carboline by Oxidative Enzymes" @default.
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• W2148462089 doi "https://doi.org/10.1155/2013/248608" @default.
• W2148462089 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3745933" @default.
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• W2148462089 hasPublicationYear "2013" @default.
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