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

Journal article

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.

Authors: Schroeder, M; Atherton, H; Dodd, M; Lee, P; Cochlin, L

• Publication status: Published
• Journal: Circulation. Cardiovascular imaging
• Volume: 5
• Issue: 2
• Pages: 201-209
• Publication date: 2012-03-01
• DOI: 10.1161/circimaging.111.969451
• EISSN: 1942-0080
• ISSN: 1941-9651
• Language: English
• Keywords: Acetylcarnitine; Glutamic Acid; Energy Metabolism; Citric Acid; Animals; Carbon Isotopes; Rats; Time Factors; Myocardial Contraction; Rats, Wistar; Acetyl Coenzyme A; Male; Pyruvic Acid; Pyruvate Dehydrogenase Complex; Magnetic Resonance Spectroscopy; Carnitine O-Acetyltransferase; Oxidation-Reduction; Myocardium; Postprandial Period