Erschienen in:
01.04.2009 | Original Article
Assessment of mitochondrial respiratory chain function in hyperphenylalaninaemia
verfasst von:
N. Kyprianou, E. Murphy, P. Lee, I. Hargreaves
Erschienen in:
Journal of Inherited Metabolic Disease
|
Ausgabe 2/2009
Einloggen, um Zugang zu erhalten
Summary
Phenylketonuria (PKU) is an autosomal recessive disorder resulting in neurological and intellectual disability when untreated. However, even in treated patients there may be residual neurological impairment such as tremor. It has been suggested that the hyperphenylalaninaemia in patients with PKU reduces complex I (NADH:ubiquinone reductase) activity of the mitochondrial respiratory chain (MRC) and/or biosynthesis of coenzyme Q10 (CoQ10), which acts as an electron carrier in the MRC, leading to impaired energy metabolism in the brain of patients with PKU and hence the neurological pathology. The aim of this study was to elucidate the mechanism of phenylalanine (Phe) toxicity on the MRC. We compared mean plasma and blood-spot Phe and mononuclear CoQ10 levels in 17 patients with PKU and a tremor compared to 22 patients without tremor. Human 1321N1 astrocytoma cells were exposed to hyperphenylalaninaemia by the addition of 300 or 900 μmol/L of Phe to the cell culture medium. Following 96 h of culture we measured complex I and citrate synthase activities and CoQ10 level. Results showed no significant difference in Phe or CoQ10 levels in patients with tremor compared to those without tremor. Further, hyperphenylalaninaemia did not cause a significant reduction in complex I activity or CoQ10 biosynthesis, even when taking into account the mitochondrial enrichment of the cell samples by expressing complex I and CoQ10 as a ratio to citrate synthase. In conclusion, the results of this study suggest that hyperphenylalaninaemia does not contribute to the pathophysiology of PKU by causing a decrease in MRC complex I activity and/or CoQ10 biosynthesis.