CONTRIBUTION OF OXIDATIVE-METABOLISM AND GLYCOLYSIS TO ATP PRODUCTION IN HYPERTROPHIED HEARTS
CONTRIBUTION OF OXIDATIVE-METABOLISM AND GLYCOLYSIS TO ATP PRODUCTION IN HYPERTROPHIED HEARTS
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DOI：
10.1152/ajpheart.1994.267.2.h742
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发表时间：
1994-08-01
影响因子：
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通讯作者：
LOPASCHUK, GD
中科院分区：
文献类型：
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作者：
ALLARD, MF;SCHONEKESS, BO;LOPASCHUK, GD
糖酵解和氧化代谢对ATP产生的贡献在用含有3%白蛋白、0.4 mM棕榈酸盐、0.5 mM乳酸盐和11 mM葡萄糖的Krebs-Henseleit缓冲液灌注的离体肥大心脏中测定。通过用[5-H-3/U-C-14]葡萄糖灌注心脏并通过分别测量（H2O）-H-3和（CO2）-C-14的产生来直接测量糖酵解和葡萄糖氧化。通过同时测量[9，10-H-3]棕榈酸和[U-C-14]乳酸灌注心脏中的（H2O）-H-3和（CO2）-C-14来测定棕榈酸和乳酸氧化。在低工作负荷（60 mmHg主动脉后负荷），棕榈酸氧化率在肥厚心脏比对照心脏低47%，但棕榈酸氧化仍然是两组的主要能源，分别占总ATP产量的55%和69%。糖酵解对ATP产生的贡献在肥大心脏中（19%）显著高于对照心脏（7%），而葡萄糖和乳酸氧化在两组之间没有差异。在高工作条件下（120 mmHg主动脉后负荷），机械功能所需的额外ATP生产主要来自两组中葡萄糖和乳酸盐氧化的增加。棕榈酸氧化对总体ATP产生的贡献在肥大和对照心脏中降低（分别为总体ATP产生的40%和55%），并且在肥大心脏中不再显着抑制。另一方面，糖酵解在对照心脏中加速到在肥大心脏中观察到的速率。因此，脂肪酸氧化对肥大大鼠心脏能量产生的贡献减少，伴随着糖酵解在低工作条件下的补偿性增加。在较高的工作负荷下，心肌对ATP产生的需求增加克服了这些代谢差异。
The contribution of glycolysis and oxidative metabolism to ATP production was determined in isolated working hypertrophied hearts perfused with Krebs-Henseleit buffer containing 3% albumin, 0.4 mM palmitate, 0.5 mM lactate, and 11 mM glucose. Glycolysis and glucose oxidation were directly measured by perfusing hearts with [5-H-3/U-C-14]glucose and by measuring (H2O)-H-3 and (CO2)-C-14 production, respectively. Palmitate and lactate oxidation were determined by simultaneous measurement of (H2O)-H-3 and (CO2)-C-14 in hearts perfused with [9,10-H-3]palmitate and [U-C-14]lactate. At low workloads (60 mmHg aortic afterload), rates of palmitate oxidation were 47% lower in hypertrophied hearts than in control hearts, but palmitate oxidation remained the primary energy source in both groups, accounting for 55 and 69% of total ATP production, respectively. The contribution of glycolysis to ATP production was significantly higher in hypertrophied hearts (19%) than in control hearts (7%), whereas that of glucose and lactate oxidation did not differ between groups. During conditions of high work (120 mmHg aortic afterload), the extra ATP production required for mechanical function was obtained primarily from an increase in the oxidation of glucose and lactate in both groups. The contribution of palmitate oxidation to overall ATP production decreased in hypertrophied and control hearts (to 40 and 55% of overall ATP production, respectively) and was no longer significantly depressed in hypertrophied hearts. Glycolysis, on the other hand, was accelerated in control hearts to rates seen in the hypertrophied hearts. Thus a reduced contribution of fatty acid oxidation to energy production in hypertrophied rat hearts is accompanied by a compensatory increase in glycolysis during low work conditions. At higher workloads, the increased myocardial demand for ATP production overcomes these metabolic differences.