Broderick T L, Quinney H A, Lopaschuk G D
Department of Exercise Physiology, University of Alberta, Edmonton, Canada.
J Biol Chem. 1992 Feb 25;267(6):3758-63.
The effects of L-carnitine on myocardial glycolysis, glucose oxidation, and palmitate oxidation were determined in isolated working rat hearts. Hearts were perfused under aerobic conditions with perfusate containing either 11 mM [2-3H/U-14C]glucose in the presence or absence of 1.2 mM palmitate or 11 mM glucose and 1.2 mM [1-14C]palmitate. Myocardial carnitine levels were elevated by perfusing hearts with 10 mM L-carnitine. A 60-min perfusion period resulted in significant increases in total myocardial carnitine from 4376 +/- 211 to 9496 +/- 473 nmol/g dry weight. Glycolysis (measured as 3H2O production) was unchanged in carnitine-treated hearts perfused in the absence of fatty acids (4418 +/- 300 versus 4547 +/- 600 nmol glucose/g dry weight.min). If 1.2 mM palmitate was present in the perfusate, glycolysis decreased almost 2-fold compared with hearts perfused in the absence of fatty acids. In carnitine-treated hearts this drop in glycolysis did not occur (glycolytic rates were 2911 +/- 231 to 4629 +/- 460 nmol glucose/g dry weight.min, in control and carnitine-treated hearts, respectively. Compared with control hearts, glucose oxidation rates (measured as 14CO2 production from [U-14C]glucose) were unaltered in carnitine-treated hearts perfused in the absence of fatty acids (1819 +/- 169 versus 2026 +/- 171 nmol glucose/g dry weight.min, respectively). In the presence of 1.2 mM palmitate, glucose oxidation decreased dramatically in control hearts (11-fold). In carnitine-treated hearts, however, glucose oxidation was significantly greater than control hearts under these conditions (158 +/- 21 to 454 +/- 85 nmol glucose/g dry weight.min, in control and carnitine-treated hearts, respectively). Palmitate oxidation rates (measured as 14CO2 production from [1-14C]palmitate) decreased in the carnitine-treated hearts from 728 +/- 61 to 572 +/- 111 nmol palmitate/g dry weight.min. This probably occurred secondary to an increase in overall ATP production from glucose oxidation (from 5.4 to 14.5% of steady state myocardial ATP production). The results reported in this study provide direct evidence that carnitine can stimulate glucose oxidation in the intact fatty acid perfused heart. This probably occurs secondary to facilitating the intramitochondrial transfer of acetyl groups from acetyl-CoA to acetylcarnitine, thereby relieving inhibition of the pyruvate dehydrogenase complex.
在离体工作的大鼠心脏中测定了左旋肉碱对心肌糖酵解、葡萄糖氧化和棕榈酸氧化的影响。心脏在有氧条件下用含有11 mM [2-³H/U-¹⁴C]葡萄糖的灌注液灌注，灌注液中存在或不存在1.2 mM棕榈酸，或含有11 mM葡萄糖和1.2 mM [1-¹⁴C]棕榈酸。通过用10 mM左旋肉碱灌注心脏来提高心肌肉碱水平。60分钟的灌注期导致心肌总肉碱从4376±211显著增加至9496±473 nmol/g干重。在无脂肪酸灌注的肉碱处理心脏中，糖酵解（以³H₂O产生量衡量）未发生变化（分别为4418±300与4547±600 nmol葡萄糖/g干重·分钟）。如果灌注液中存在1.2 mM棕榈酸，与无脂肪酸灌注的心脏相比，糖酵解下降了近2倍。在肉碱处理的心脏中，这种糖酵解下降并未发生（对照和肉碱处理心脏的糖酵解速率分别为2911±231至4629±460 nmol葡萄糖/g干重·分钟）。与对照心脏相比，在无脂肪酸灌注的肉碱处理心脏中，葡萄糖氧化速率（以[U-¹⁴C]葡萄糖产生的¹⁴CO₂量衡量）未发生改变（分别为1819±169与2026±171 nmol葡萄糖/g干重·分钟）。在存在1.2 mM棕榈酸的情况下，对照心脏中的葡萄糖氧化显著下降（11倍）。然而，在肉碱处理的心脏中，在这些条件下葡萄糖氧化显著高于对照心脏（对照和肉碱处理心脏分别为158±21至454±85 nmol葡萄糖/g干重·分钟）。肉碱处理心脏中的棕榈酸氧化速率（以[1-¹⁴C]棕榈酸产生的¹⁴CO₂量衡量）从728±61降至572±111 nmol棕榈酸/g干重·分钟。这可能继发于葡萄糖氧化产生的总ATP增加（从稳态心肌ATP产生的5.4%增至14.5%）。本研究报告的结果提供了直接证据，表明肉碱可刺激完整脂肪酸灌注心脏中的葡萄糖氧化。这可能继发于促进乙酰基从乙酰辅酶A在线粒体内向乙酰肉碱的转移，从而解除对丙酮酸脱氢酶复合物的抑制。
