The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study.
Circ Cardiovasc Imaging
; 5(2): 201-9, 2012 Mar.
Article
em En
| MEDLINE
| ID: mdl-22238215
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 ANDRESULTS:
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.
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Base de dados:
MEDLINE
Assunto principal:
Acetilcoenzima A
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Acetilcarnitina
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Complexo Piruvato Desidrogenase
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Espectroscopia de Ressonância Magnética
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Carnitina O-Acetiltransferase
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Metabolismo Energético
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Miocárdio
Idioma:
En
Ano de publicação:
2012
Tipo de documento:
Article