Propionic acidemia occasionally produces a toxic encephalopathy resembling Reye's syndrome, indicating disruption of mitochondrial metabolism. Liver mitochondria respiratory control ratios were reduced 46% by 5 mm propionate; inhibition correlated with matrix propionyl-CoA levels. l-Malate prevented the toxic effect of propionate and reduced the propionyl-CoA matrix concentration by 62%. The beneficial effect of l-malate is apparently due to stimulation of succinate efflux because the effect is blocked by benzylmalonate, an inhibitor of the dicarboxylate carrier. Matrix concentration of label from [1-14C]propionate was not affected by l-malate and/or benzylmalonate. l-Malate may be useful in the treatment of patients with propionic acidemia.
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism