title: The effect of malate on propionate mitochondrial toxicity.
abstract: 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.
authors.affiliation: Division of Neurology, Children's Memorial Hospital, Northwestern University Medical School, Chicago, Illinois 60611.
authors.forename: T
authors.initials: T
authors.lastname: Matsuishi
authors.forename: D A
authors.initials: DA
authors.lastname: Stumpf
authors.forename: K
authors.initials: K
authors.lastname: Chrislip
mesh_terms: D000214:Acyl Coenzyme A / Q000378:metabolism; D006801:Humans; D008293:Malates / Q000494:pharmacology*; D008930:Mitochondria, Liver / Q000187:drug effects*; D010084:Oxidation-Reduction; D011422:Propionates / Q000037:antagonists & inhibitors*
chemical_list: D000214:Acyl Coenzyme A; D008293:Malates; D011422:Propionates; C030298:malic acid