通过乙酰肉碱缓冲剂循环乙酰辅酶 A 以缓冲心脏底物供应：一项基于 13C 磁共振的极化研究。
The cycling of acetyl-coenzyme A through acetylcarnitine buffers cardiac substrate supply: a hyperpolarized 13C magnetic resonance study.
机构信息
Cardiac Metabolism Research Group, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, UK.
出版信息
Circ Cardiovasc Imaging. 2012 Mar;5(2):201-9. doi: 10.1161/CIRCIMAGING.111.969451. Epub 2012 Jan 11.
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.
背景
肉碱乙酰转移酶催化可逆的乙酰辅酶 A（CoA）转化为乙酰肉碱。本研究的目的是使用代谢示踪剂超极化[2-（13）]丙酮酸磁共振波谱来确定肉碱乙酰转移酶是否有助于心脏中的碳水化合物氧化。
方法和结果
在离体实验中，在超极化[2-（13）]丙酮酸输注后，用射频脉冲饱和[1-（13）]乙酰肉碱共振，并观察这种饱和对[1-（13）]柠檬酸和[5-（13）]谷氨酸的影响。在体内，将[2-（13）]丙酮酸输注到三组进食雄性 Wistar 大鼠中：（1）对照组，（2）二氯乙酸增强丙酮酸脱氢酶通量的大鼠，（3）多巴酚丁胺升高心脏工作量的大鼠。在灌流心脏中，[1-（13）]乙酰肉碱饱和使[1-（13）]柠檬酸和[5-（13）]谷氨酸共振分别降低 63%和 51%，表明丙酮酸衍生的乙酰-CoA 和乙酰肉碱池之间快速交换。在体内，二氯乙酸使[1-（13）]乙酰肉碱的产生速率增加了 35%，并使乙酰肉碱池的总体大小增加了 33%。多巴酚丁胺使[1-（13）]乙酰肉碱的产生速率降低了 37%，并使乙酰肉碱池的大小降低了 40%。
结论
超极化（13）C 磁共振波谱显示，乙酰肉碱为多余的乙酰-CoA 提供了一种处置途径，并且在心脏工作量增加时为补充乙酰-CoA 提供了一种途径。通过乙酰肉碱循环乙酰-CoA 似乎是使瞬时乙酰-CoA 供应与代谢需求相匹配的关键，从而有助于平衡心肌底物供应和收缩功能。
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