The enzymatic activities of brain catechol-O-methyltransferase (COMT) and methionine sulphoxide reductase are correlated in a COMT Val/Met allele-dependent fashion.
Neuropathol Appl Neurobiol
; 41(7): 941-51, 2015 Dec.
Article
en En
| MEDLINE
| ID: mdl-25640985
ABSTRACT
AIMS:
The enzyme catechol-O-methyltransferase (COMT) plays a primary role in the metabolism of catecholamine neurotransmitters and is implicated in the modulation of cognitive and emotional responses. The best characterized single nucleotide polymorphism (SNP) of the COMT gene consists of a valine (Val)-to-methionine (Met) substitution at codon 108/158. The Met-containing variant confers a marked reduction in COMT catalytic activity. We recently showed that the activity of recombinant COMT is positively regulated by the enzyme Met sulphoxide reductase (MSR), which counters the oxidation of Met residues of proteins. The current study was designed to assess whether brain COMT activity may be correlated to MSR in an allele-dependent fashion.METHODS:
COMT and MSR activities were measured from post-mortem samples of prefrontal cortices, striata and cerebella of 32 subjects by using catechol and dabsyl-Met sulphoxide as substrates, respectively. Allelic discrimination of COMT Val(108/185) Metâ SNP was performed using the Taqman 5'nuclease assay.RESULTS:
Our studies revealed that, in homozygous carriers of Met, but not Val alleles, the activity of COMT and MSR was significantly correlated throughout all tested brain regions.CONCLUSION:
These results suggest that the reduced enzymatic activity of Met-containing COMT may be secondary to Met sulphoxidation and point to MSR as a key molecular determinant for the modulation of COMT activity.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Encéfalo
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Catecol O-Metiltransferasa
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Polimorfismo de Nucleótido Simple
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Metionina Sulfóxido Reductasas
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Genotipo
Límite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Neuropathol Appl Neurobiol
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos