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Metabolite profile resulting from the activation/inactivation of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 2-methyltetrahydro-ß-carboline by oxidative enzymes.
Herraiz, Tomás; Guillén, Hugo; Galisteo, Juan.
Afiliação
  • Herraiz T; Instituto de Ciencia y Tecnología de Alimentos y Nutrición, Consejo Superior de Investigaciones Científicas, Juan de la Cierva 3, 28006 Madrid, Spain. therraiz@ictan.csic.es
Biomed Res Int ; 2013: 248608, 2013.
Article em En | MEDLINE | ID: mdl-23984327
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-ß-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 ß-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-ß-carboline to 2-methyl-3,4-dihydro-ß-carbolinium cation (2-Me-3,4-DH ß C(+)). These substances were inactivated by cytochrome P450 2D6 through N-demethylation and aromatic hydroxylation (MPTP) and aromatic hydroxylation (2-methyltetrahydro-ß-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--ß--carbolinium- ßC(+)-) by MAO and heme peroxidases and the rate of inactivation (i.e., N-demethylation, aromatic hydroxylation) by cytochrome P450 2D6.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carbolinas / 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina / Enzimas / Metabolômica Limite: Humans Idioma: En Revista: Biomed Res Int Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Espanha

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Carbolinas / 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina / Enzimas / Metabolômica Limite: Humans Idioma: En Revista: Biomed Res Int Ano de publicação: 2013 Tipo de documento: Article País de afiliação: Espanha