The gene mutated in l-2-hydroxyglutaric aciduria encodes l-2-hydroxyglutarate dehydrogenase.
Biochimie
; 88(1): 113-6, 2006 Jan.
Article
em En
| MEDLINE
| ID: mdl-16005139
ABSTRACT
The biochemical defect in L-2-hydroxyglutaric aciduria is still unknown, but the mutated gene has recently been identified on chromosome 14q22. Transfection of human embryonic kidney (HEK) cells with a cDNA encoding the product of the human gene led to a>15-fold increase in L-2-hydroxyglutarate dehydrogenase activity. The overexpressed enzyme had similar biochemical characteristics (including sensitivity to FAD and association with membranes) as the rat liver enzyme. Western blot analysis indicated that it is processed through the removal of a N-terminal approximately 4 kDa fragment, in agreement with a mitochondrial localization. Transfection experiments indicated that the mutations (K81E, E176D, Delta-exon9) found in patients with L-2-hydroxyglutaric aciduria suppressed L-2-hydroxyglutarate dehydrogenase activity. Western blot analysis showed that the three mutated proteins were expressed to various degrees in HEK cells, but were abnormally processed. Taken together, these data indicate that L-2-hydroxyglutaric aciduria is due to a deficiency in L-2-hydroxyglutarate dehydrogenase.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Oxirredutases do Álcool
/
Glutaratos
Tipo de estudo:
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Biochimie
Ano de publicação:
2006
Tipo de documento:
Article
País de afiliação:
Bélgica