The Cycling of Acetyl-Coenzyme A Through Acetylcarnitine Buffers Cardiac Substrate Supply A Hyperpolarized 13 C Magnetic Resonance Study

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- 13 C]pyruvate with magnetic resonance spectroscopy to determine whether carnitine acetyltransferase fa...

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Published inCirculation. Cardiovascular imaging Vol. 5; no. 2; pp. 201 - 209
Main Authors Schroeder, Marie A., Atherton, Helen J., Dodd, Michael S., Lee, Phillip, Cochlin, Lowri E., Radda, George K., Clarke, Kieran, Tyler, Damian J.
Format Journal Article
LanguageEnglish
Published 01.03.2012
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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- 13 C]pyruvate with magnetic resonance spectroscopy to determine whether carnitine acetyltransferase facilitates carbohydrate oxidation in the heart. Methods and Results— Ex vivo, following hyperpolarized [2- 13 C]pyruvate infusion, the [1- 13 C]acetylcarnitine resonance was saturated with a radiofrequency pulse, and the effect of this saturation on [1- 13 C]citrate and [5- 13 C]glutamate was observed. In vivo, [2- 13 C]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- 13 C]acetylcarnitine saturation reduced the [1- 13 C]citrate and [5- 13 C]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- 13 C]acetylcarnitine production by 35% and increased the overall acetylcarnitine pool size by 33%. Dobutamine decreased the rate of [1- 13 C]acetylcarnitine production by 37% and decreased the acetylcarnitine pool size by 40%. Conclusions— Hyperpolarized 13 C 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.
AbstractList 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- 13 C]pyruvate with magnetic resonance spectroscopy to determine whether carnitine acetyltransferase facilitates carbohydrate oxidation in the heart. Methods and Results— Ex vivo, following hyperpolarized [2- 13 C]pyruvate infusion, the [1- 13 C]acetylcarnitine resonance was saturated with a radiofrequency pulse, and the effect of this saturation on [1- 13 C]citrate and [5- 13 C]glutamate was observed. In vivo, [2- 13 C]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- 13 C]acetylcarnitine saturation reduced the [1- 13 C]citrate and [5- 13 C]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- 13 C]acetylcarnitine production by 35% and increased the overall acetylcarnitine pool size by 33%. Dobutamine decreased the rate of [1- 13 C]acetylcarnitine production by 37% and decreased the acetylcarnitine pool size by 40%. Conclusions— Hyperpolarized 13 C 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.
Author Cochlin, Lowri E.
Lee, Phillip
Schroeder, Marie A.
Atherton, Helen J.
Clarke, Kieran
Tyler, Damian J.
Dodd, Michael S.
Radda, George K.
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  givenname: Michael S.
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  givenname: Phillip
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Subtitle A Hyperpolarized 13 C Magnetic Resonance Study
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