The effect of malate on propionate mitochondrial toxicity.
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.
Matsuishi
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T
Division of Neurology, Children's Memorial Hospital, Northwestern University Medical School, Chicago, Illinois 60611.
Stumpf
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DA
Chrislip
K
K
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*
D000214:Acyl Coenzyme A; D008293:Malates; D011422:Propionates; C030298:malic acid