Abstract
The biochemical abnormalities in vitamine dependencies are poorly understood. Defects of coenzyme synthesis or transport improved by mass action, compensation of decreased affinity of the apoenzyme for its coenzyme and stabilization of a mutant apoenzyme by high concentrations of coenzyme are some of the mechanisms discussed. - Fibroblast cultures from two children suffering from congenital lactic acidosis responding well to very high doses of Th (50 - 100 mg/kg/d) were studied. Reduced CO2-production from 1,14C-pyruvate and deficient activity of PDH-complex were found. Culture of these fibroblasts in the presence of high concentrations of Th (0.4 μg/ml) resulted in stimulation (20 - 100 %) of pyruvate decarboxylation in both systems. This effect could not be prevented by puromycin (50 μg/ml), an inhibitor of protein synthesis. Surprisingly the same result was also obtained in normal cell lines. Furthermore the same effect could also be demonstrated for 2-oxoglutaricaciddehydrogenase and for 2-oxoisocaproicaciddehydrogenase. - The type of activation mechanism involved is not yet clear. In the case of PDH activation might be due to the conversion of the enzyme complex to the dephosphorylated (i.e. activated) form by high concentrations of thiaminepyro-phosphate. The clinically relevant conclusion is that in any patient with a partial deficiency of one of these dehydrogenases a therapeutic trial with very high doses of Th is warranted.
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Wick, H., Baumgartner, R. Thiamine (Th) dependent pyruvatedehydrogenase (PDH) deficiency: 3. Pediatr Res 14, 167 (1980). https://doi.org/10.1203/00006450-198002000-00030
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DOI: https://doi.org/10.1203/00006450-198002000-00030
