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: T Matsuishi, D A Stumpf, K Chrislip
• Journal: Biochemical medicine and metabolic biology (Biochem Med Metab Biol) Vol. 46 Issue 2 Pg. 177-84 (Oct 1991) ISSN: 0885-4505 [Print] United States
• PMID: 1782009 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Acyl Coenzyme A
• Malates
• Propionates
• malic acid

Topics

• Acyl Coenzyme A (metabolism)
• Humans
• Malates (pharmacology)
• Mitochondria, Liver (drug effects)
• Oxidation-Reduction
• Propionates (antagonists & inhibitors)