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