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Propionate-induced changes in cardiac metabolism, notably CoA trapping, are not altered by l-carnitine.

Publication ,  Journal Article
Wang, Y; Christopher, BA; Wilson, KA; Muoio, D; McGarrah, RW; Brunengraber, H; Zhang, G-F
Published in: Am J Physiol Endocrinol Metab
October 1, 2018

High concentrations of propionate and its metabolites are found in several diseases that are often associated with the development of cardiac dysfunction, such as obesity, diabetes, propionic acidemia, and methylmalonic acidemia. In the present work, we employed a stable isotope-based metabolic flux approach to understand propionate-mediated perturbation of cardiac energy metabolism. Propionate led to accumulation of propionyl-CoA (increased by ~101-fold) and methylmalonyl-CoA (increased by 36-fold). This accumulation caused significant mitochondrial CoA trapping and inhibited fatty acid oxidation. The reduced energy contribution from fatty acid oxidation was associated with increased glucose oxidation. The enhanced anaplerosis of propionate and CoA trapping altered the pool sizes of tricarboxylic acid cycle (TCA) metabolites. In addition to being an anaplerotic substrate, the accumulation of proprionate-derived malate increased the recycling of malate to pyruvate and acetyl-CoA, which can enter the TCA for energy production. Supplementation of 3 mM l-carnitine did not relieve CoA trapping and did not reverse the propionate-mediated fuel switch. This is due to new findings that the heart appears to lack the specific enzyme catalyzing the conversion of short-chain (C3 and C4) dicarboxylyl-CoAs to dicarboxylylcarnitines. The discovery of this work warrants further investigation on the relevance of dicarboxylylcarnitines, especially C3 and C4 dicarboxylylcarnitines, in cardiac conditions such as heart failure.

Duke Scholars

Published In

Am J Physiol Endocrinol Metab

DOI

EISSN

1522-1555

Publication Date

October 1, 2018

Volume

315

Issue

4

Start / End Page

E622 / E633

Location

United States

Related Subject Headings

  • Rats
  • Pyruvic Acid
  • Propionates
  • Oxidation-Reduction
  • Myocardium
  • Mitochondria, Heart
  • Metabolic Flux Analysis
  • Male
  • Malates
  • Liver
 

Citation

APA
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ICMJE
MLA
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Wang, Y., Christopher, B. A., Wilson, K. A., Muoio, D., McGarrah, R. W., Brunengraber, H., & Zhang, G.-F. (2018). Propionate-induced changes in cardiac metabolism, notably CoA trapping, are not altered by l-carnitine. Am J Physiol Endocrinol Metab, 315(4), E622–E633. https://doi.org/10.1152/ajpendo.00081.2018
Wang, Yingxue, Bridgette A. Christopher, Kirkland A. Wilson, Deborah Muoio, Robert W. McGarrah, Henri Brunengraber, and Guo-Fang Zhang. “Propionate-induced changes in cardiac metabolism, notably CoA trapping, are not altered by l-carnitine.Am J Physiol Endocrinol Metab 315, no. 4 (October 1, 2018): E622–33. https://doi.org/10.1152/ajpendo.00081.2018.
Wang Y, Christopher BA, Wilson KA, Muoio D, McGarrah RW, Brunengraber H, et al. Propionate-induced changes in cardiac metabolism, notably CoA trapping, are not altered by l-carnitine. Am J Physiol Endocrinol Metab. 2018 Oct 1;315(4):E622–33.
Wang, Yingxue, et al. “Propionate-induced changes in cardiac metabolism, notably CoA trapping, are not altered by l-carnitine.Am J Physiol Endocrinol Metab, vol. 315, no. 4, Oct. 2018, pp. E622–33. Pubmed, doi:10.1152/ajpendo.00081.2018.
Wang Y, Christopher BA, Wilson KA, Muoio D, McGarrah RW, Brunengraber H, Zhang G-F. Propionate-induced changes in cardiac metabolism, notably CoA trapping, are not altered by l-carnitine. Am J Physiol Endocrinol Metab. 2018 Oct 1;315(4):E622–E633.

Published In

Am J Physiol Endocrinol Metab

DOI

EISSN

1522-1555

Publication Date

October 1, 2018

Volume

315

Issue

4

Start / End Page

E622 / E633

Location

United States

Related Subject Headings

  • Rats
  • Pyruvic Acid
  • Propionates
  • Oxidation-Reduction
  • Myocardium
  • Mitochondria, Heart
  • Metabolic Flux Analysis
  • Male
  • Malates
  • Liver