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

Research output: Contribution to journalArticle

60 Citations (Scopus)

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

Fingerprint

Acetylcarnitine
Acetyl Coenzyme A
Buffers
Magnetic Resonance Spectroscopy
Pyruvic Acid
Carnitine O-Acetyltransferase
Dobutamine
Workload
Citric Acid
Glutamic Acid
Wistar Rats
Oxidoreductases
Carbohydrates

Keywords

  • Acetylcarnitine
  • Imaging
  • Magnetic resonance spectroscopy
  • Metabolism

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Cardiology and Cardiovascular Medicine

Cite this

The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply : A hyperpolarized 13C magnetic resonance study. / Schroeder, Marie A.; Atherton, Helen J.; Dodd, Michael S.; Lee, Phillip; Cochlin, Lowri E.; Radda, George K.; Clarke, Kieran; Tyler, Damian J.

In: Circulation: Cardiovascular Imaging, Vol. 5, No. 2, 01.03.2012, p. 201-209.

Research output: Contribution to journalArticle

Schroeder, Marie A. ; Atherton, Helen J. ; Dodd, Michael S. ; Lee, Phillip ; Cochlin, Lowri E. ; Radda, George K. ; Clarke, Kieran ; Tyler, Damian J. / The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply : A hyperpolarized 13C magnetic resonance study. In: Circulation: Cardiovascular Imaging. 2012 ; Vol. 5, No. 2. pp. 201-209.
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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.",
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AU - Dodd, Michael S.

AU - Lee, Phillip

AU - Cochlin, Lowri E.

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AU - Clarke, Kieran

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AB - 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.

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