Mitochondrial involvement and erythronic acid as a novel biomarker in transaldolase deficiency.
Biochim Biophys Acta
; 1802(11): 1028-35, 2010 Nov.
Article
em En
| MEDLINE
| ID: mdl-20600873
ABSTRACT
BACKGROUND:
Sedoheptulose, arabitol, ribitol, and erythritol have been identified as key diagnostic metabolites in TALDO deficiency.METHOD:
Urine from 6 TALDO-deficient patients and TALDO-deficient knock-out mice were analyzed using ¹H-NMR spectroscopy and GC-mass spectrometry.RESULTS:
Our data confirm the known metabolic characteristics in TALDO-deficient patients. The ß-furanose form was the major sedoheptulose anomer in TALDO-deficient patients. Erythronic acid was identified as a major abnormal metabolite in all patients and in knock-out TALDO mice implicating an as yet unknown biochemical pathway in this disease. A putative sequence of enzymatic reactions leading to the formation of erythronic acid is presented. The urinary concentration of the citric acid cycle intermediates 2-oxoglutaric acid and fumaric acid was increased in the majority of TALDO-deficient patients but not in the knock-out mice.CONCLUSION:
Erythronic acid is a novel and major hallmark in TALDO deficiency. The pathway leading to its production may play a role in healthy humans as well. In TALDO-deficient patients, there is an increased flux through this pathway. The finding of increased citric acid cycle intermediates hints toward a disturbed mitochondrial metabolism in TALDO deficiency.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transaldolase
/
Butiratos
/
Biomarcadores
/
Mitocôndrias
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Animals
/
Child, preschool
/
Humans
/
Infant
/
Newborn
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article