L-Propionyl-carnitine protection of mitochondria in ischemic rat hearts

  • Fabio Di Lisa
  • Roberta Menabò
  • Noris Siliprandi
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 5)


The energy-linked processes (transmembrane potential and oxidative phosphorylation) resulted in impaired mitochondria isolated from ischemic perfused rat hearts. Addition of 1.5 mM L-propionyl-carnitine to the perfusate significantly reduced the ischemic damage and ameliorated mitochondrial Ca2+ homeostasis. In both normoxic and ischemic hearts perfused with L-propionyl-carnitine a consistent amount of propionyl-CoA — otherwise undetectable — was produced. L-propionyl-carnitine treatment also prevented the decrease of succinyl-CoA associated with the ischemic condition. These results and the decrease of myocardial acetyl-CoA induced by exogenous L-propionyl-carnitine points to the anaplerotic effect of this ester. The consequently improved flux in the tricarboxylic-acid cycle may account for the observed protection of mitochondrial functions afforded by L-propionyl-carnitine in the ischemic perfused hearts.

Key words

L-propionyl-carnitine mitochondrial membrane potential mitochondrial Ca2+ short-chain acyl-CoA long-chain acyl-CoA perfused rat heart ischemia 







N-2-hydroxyethylpiperazine-N’-2-ethanesulfonic acid


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Siliprandi N, Sartorelli L, Ciman M, Di Lisa F: Carnitine: metabolism and clinical chemistry. Clin Chim Acta, in pressGoogle Scholar
  2. 2.
    Siliprandi N, Siliprandi D, Ciman M: Stimulation of oxidation of mitochondrial fatty acids and acetate by acetyl-carnitine. Biochem J 96: 777–780, 1965PubMedGoogle Scholar
  3. 3.
    Pontremoli S, Melloni E, Michetti M, Sparatore B, Salamino F, Siliprandi N, Horecker B: Isovaleryl-carnitine is a specific activator of calpain of human neutrophils. Biochim Biophys Res Comm 148: 1189–1195, 1987CrossRefGoogle Scholar
  4. 4.
    Liedtke JA: Alterations of carbohydrate and lipid metabolism in the acutely ischemic heart. Prog Cardiovasc Dis 23: 321–336, 1981PubMedCrossRefGoogle Scholar
  5. 5.
    Paulson DJ, Traxler J, Schmidt M, Noonan J, Shug AL: Protection of the ischaemic myocardium by L-propionylcarnitine: effects on the recovery of cardiac output after ischemia and reperfusion, carnitine transport and fatty acid oxidation. Cardiovasc Res 20: 536–541, 1986PubMedCrossRefGoogle Scholar
  6. 6.
    Liedtke AJ, Demaison L, Nellis SH: Effects of L-propionylcarnitine on mechanical recovery during reflow in intact hearts. Am J Physiol 255: 169–176, 1988Google Scholar
  7. 7.
    Fallen EL, Elliot WC, Gorlin R: Apparatus for study of ventricular function and metabolism in the isolated perfused rat heart. J Appl Physiol 22: 836–839, 1967PubMedGoogle Scholar
  8. 8.
    Lindenmayer GE, Sordahl LA, Schwartz A: Reevaluation of oxidative phosphorylation in cardiac mitochondria from normal animals and animals in heart failure. Circ Res 23: 439–450, 1968PubMedGoogle Scholar
  9. 9.
    Gornall AG, Bardawill CJ, David MM: Determination of serum proteins by means of the biuret reaction. J Biol Chem 177: 751–766, 1949PubMedGoogle Scholar
  10. 10.
    Kamo N, Muratsugu M, Hongoh R, Kobatake Y: Membrane potential of mitochondria measured with an electrode sensitive to tetraphenyl phosphonium and relationship between proton electrochemical potential and phosphorylation potential in steady state. J Membr Biol 49: 105–121, 1979PubMedCrossRefGoogle Scholar
  11. 11.
    Jensen BD, Gunter KK, Gunter TE: The efficiencies of the component steps of oxidative phosphorylation. Arch Biochem Biophys 248: 305–323, 1986PubMedCrossRefGoogle Scholar
  12. 12.
    Ferrari R, Di Lisa F, Raddino R, Visioli O: The effects of Ruthenium Red on mitochondrial function during post-ishemic reperfusion. J Mol Cell Cardiol 14: 737–740, 1982PubMedCrossRefGoogle Scholar
  13. 13.
    Lysiak W, Lilly K, Di Lisa F, Toth PP, Bieber LL: Quantitation of the effect of L-carnitine on the levels of acid-soluble short-chain acyl-CoA and CoASH in rat heart and liver mitochondria. J Biol Chem 263: 1151–1156, 1988PubMedGoogle Scholar
  14. 14.
    Veloso D, Veech RL: Stoichiometric hydrolysis of long chaing acyl-CoA and measurement of the CoA formed with an enzymatic cyling method. Anal Biochem 62: 449–460, 1974PubMedCrossRefGoogle Scholar
  15. 15.
    Penney DG, Cascarano J: Anaerobic rat heart. Effects of glucose and tricarboxylic acid-cycle metabolites on metabolism and physiological performance. Biochem J 118: 221–227, 1970PubMedGoogle Scholar
  16. 16.
    Hülsman WC, Siliprandi D, Ciman M, Siliprandi N: Effect of carnitine on the oxidation of α-oxoglutarate to succinate in the presence of acetoacetate or pyruvate. Biochim Biophys Acta 93: 166–168, 1964Google Scholar

Copyright information

© Kluwer Academic Publishers 1989

Authors and Affiliations

  • Fabio Di Lisa
    • 1
    • 2
  • Roberta Menabò
    • 1
    • 2
  • Noris Siliprandi
    • 1
    • 2
  1. 1.Centro Studio Fisiologia MitocondrialeCNRPadovaItaly
  2. 2.Dipartimento di Chimica BiologicaUniversità di PadovaItaly

Personalised recommendations