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Oxidative-phosphorylation defects in liver of patients with Wilson's disease.
- Source :
-
Lancet . 8/5/2000, Vol. 356 Issue 9228, p469-474. 6p. 3 Black and White Photographs, 2 Charts. - Publication Year :
- 2000
-
Abstract
- <bold>Background: </bold>Wilson's disease (WD) is caused by mutations in a P-type ATPase and is associated with copper deposition in liver and brain. The WD protein is present in the trans-Golgi network and may also be imported into mitochondria. The WD protein functions as a P-type copper transporting ATPase in the Golgi but any action in mitochondria is at present unknown.<bold>Methods: </bold>We studied mitochondrial function and aconitase activity in WD liver tissue and compared the results with those in a series of healthy controls and patients without WD.<bold>Findings: </bold>There was evidence of severe mitochondrial dysfunction in the livers of patients with WD. Enzyme activities were decreased as follows: complex I by 62%, complex II+III by 52%, complex IV by 33%, and aconitase by 71%. These defects did not seem to be secondary to penicillamine use, cholestasis, or poor hepatocellular synthetic function.<bold>Interpretation: </bold>The results show that there is a defect of energy metabolism in WD. The pattern of enzyme defects suggests that free-radical formation and oxidative damage, probably mediated via mitochondrial copper accumulation, are important in WD pathogenesis. These results provide a rationale for a study of the use of antioxidants in WD. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01406736
- Volume :
- 356
- Issue :
- 9228
- Database :
- Academic Search Index
- Journal :
- Lancet
- Publication Type :
- Academic Journal
- Accession number :
- 3394260
- Full Text :
- https://doi.org/10.1016/S0140-6736(00)02556-3