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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Cell culture studies on patients with mitochondrial diseases: molecular defects in pyruvate dehydrogenase.

There is a group of inborn errors of metabolism that result in the condition of chronic lacticacidemia of childhood. Nearly all of the defects that can be identified occur in mitochondrial proteins, and can be demonstrated in cultured skin fibroblasts from the patients concerned. One approach to the diagnosis of these defects involves a simple incubation of the fibroblast culture with glucose-containing medium followed by the measurement of accumulated lactate and pyruvate. The total amounts of lactate and pyruvate and the ratio between them is different in cells from patients with defects in the pyruvate dehydrogenase complex or the respiratory chain. Measurement of 1-14C-pyruvate oxidation to 14CO2 can also reveal defective oxidative metabolism. Localization of the defects can be achieved using individual assays for the enzymes concerned. The clinical sequelae of the different defects is discussed.[1]


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