The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: A hyperpolarized 13C magnetic resonance study

Marie A. Schroeder, Helen J. Atherton, Michael S. Dodd, Phillip Lee, Lowri E. Cochlin, George K. Radda, Kieran Clarke, Damian J. Tyler

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Abstract

Background-Carnitine acetyltransferase catalyzes the reversible conversion of acetyl-coenzyme A (CoA) into acetylcarnitine. The aim of this study was to use the metabolic tracer hyperpolarized [2- 13C]pyruvate with magnetic resonance spectroscopy to determine whether carnitine acetyltransferase facilitates carbohydrate oxidation in the heart. Methods and Results-Ex vivo, following hyperpolarized [2- 13C]pyruvate infusion, the [1- 13C]acetylcarnitine resonance was saturated with a radiofrequency pulse, and the effect of this saturation on [1- 13C]citrate and [5- 13C]glutamate was observed. In vivo, [2- 13C]pyruvate was infused into 3 groups of fed male Wistar rats: (1) controls, (2) rats in which dichloroacetate enhanced pyruvate dehydrogenase flux, and (3) rats in which dobutamine elevated cardiac workload. In the perfused heart, [1- 13C]acetylcarnitine saturation reduced the [1- 13C]citrate and [5- 13C]glutamate resonances by 63% and 51%, respectively, indicating a rapid exchange between pyruvate-derived acetyl-CoA and the acetylcarnitine pool. In vivo, dichloroacetate increased the rate of [1- 13C]acetylcarnitine production by 35% and increased the overall acetylcarnitine pool size by 33%. Dobutamine decreased the rate of [1- 13C]acetylcarnitine production by 37% and decreased the acetylcarnitine pool size by 40%. Conclusions-Hyperpolarized 13C magnetic resonance spectroscopy has revealed that acetylcarnitine provides a route of disposal for excess acetyl-CoA and a means to replenish acetyl-CoA when cardiac workload is increased. Cycling of acetyl-CoA through acetylcarnitine appears key to matching instantaneous acetyl-CoA supply with metabolic demand, thereby helping to balance myocardial substrate supply and contractile function.

Original languageEnglish
Pages (from-to)201-209
Number of pages9
JournalCirculation: Cardiovascular Imaging
Volume5
Issue number2
DOIs
Publication statusPublished - 1 Mar 2012
Externally publishedYes

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Keywords

  • Acetylcarnitine
  • Imaging
  • Magnetic resonance spectroscopy
  • Metabolism

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

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