Metabolite Profile Resulting from the ActivationInactivation of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 2-Methyltetrahydro-β-carboline by Oxidative Enzymes
Joint Authors
Herraiz, Tomás
Guillén, Hugo
Galisteo, Juan
Source
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-10, 10 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-07-28
Country of Publication
Egypt
No. of Pages
10
Main Subjects
Abstract EN
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-DHβC+).
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—βC+—) by MAO and heme peroxidases and the rate of inactivation (i.e., N-demethylation, aromatic hydroxylation) by cytochrome P450 2D6.
American Psychological Association (APA)
Herraiz, Tomás& Guillén, Hugo& Galisteo, Juan. 2013. Metabolite Profile Resulting from the ActivationInactivation of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 2-Methyltetrahydro-β-carboline by Oxidative Enzymes. BioMed Research International،Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-1003788
Modern Language Association (MLA)
Herraiz, Tomás…[et al.]. Metabolite Profile Resulting from the ActivationInactivation of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 2-Methyltetrahydro-β-carboline by Oxidative Enzymes. BioMed Research International No. 2013 (2013), pp.1-10.
https://search.emarefa.net/detail/BIM-1003788
American Medical Association (AMA)
Herraiz, Tomás& Guillén, Hugo& Galisteo, Juan. Metabolite Profile Resulting from the ActivationInactivation of 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 2-Methyltetrahydro-β-carboline by Oxidative Enzymes. BioMed Research International. 2013. Vol. 2013, no. 2013, pp.1-10.
https://search.emarefa.net/detail/BIM-1003788
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1003788