Inherited lactic acidosis: correction of the defect in cultured fibroblasts.
We report a case of familial lactic acidosis, lethal in the newborn period. Studies in intact fibroblasts identified a defect in the oxidative pathway of pyruvate metabolism. Although assay of pyruvate dehydrogenase on cell sonicates was not appreciably reduced, flux through the enzyme and other mitochondrial multienzyme dehydrogenases was severely impaired in intact cells. Deficient lactate conversion to carbon dioxide could be repaired by the addition to the incubation medium of electron acceptors such as methylene blue (25 micrograms/ml) or dichlorophenolindophenol (25 micrograms/ml).
D000138:Acidosis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D004579:Electron Transport; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D006801:Humans; D007231:Infant, Newborn; D007773:Lactates / Q000378:metabolism; D008751:Methylene Blue / Q000627:therapeutic use; D015324:Pyruvate Carboxylase Deficiency Disease; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D013831:Thiamine / Q000494:pharmacology; D008063:Thioctic Acid / Q000494:pharmacology
D007773:Lactates; D011768:Pyruvate Dehydrogenase Complex; D008063:Thioctic Acid; D008751:Methylene Blue; D013831:Thiamine