Propionate mitochondrial toxicity in liver and skeletal muscle: Acyl CoA levels

Toyojiro Matsuishi, David A. Stumpf*, Mohamed Seliem, Luis A. Eguren, Kathy Chrislip

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

Propionic acidemia occasionally produces a toxic encephalopathy resembling Reye syndrome, indicating disruption of mitochondrial metabolism. Understanding the mitochondrial effect of propionate might clarify the pathophysiology. Liver mitochondria are inhibited by propionate (5 mm) while muscle mitochondria are not. Preincubation is required to inhibit liver mitochondria, suggesting that propionate is metabolized to propionyl CoA. Liver and skeletal muscle mitochondria incubated with [1-14C]propionate contain similar quantities of matrix isotope and release comparable [14C]CO2. However, only liver mitochondria accumulated significant propionyl CoA, which was largely (68%) synthesized from propionate. Carnitine reduced the level of liver matrix propionyl CoA. Inhibition of respiratory control ratios by propionate correlated with propionyl CoA levels. These results support the hypothesis that acyl CoA esters are toxic and that carnitine exerts its protective effect by converting acyl CoA esters to acylcarnitine esters.

Original languageEnglish (US)
Pages (from-to)244-253
Number of pages10
JournalBiochemical Medicine and Metabolic Biology
Volume45
Issue number2
DOIs
StatePublished - Apr 1991

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry

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