The effects of increased heart work on the tricarboxylate cycle and its interactions with glycolysis in the perfused rat heart.
The effects of increased heart work on the tricarboxylate cycle and its interactions with glycolysis in the perfused rat heart.
复制标题
心脏做功增加对三羧酸循环的影响及其与灌注大鼠心脏中糖酵解的相互作用。
作者：
J. R. Neely;R. Denton;P. England;P. J. Randle
1.将Langendorff制备的主动脉压从50 mmHg升高至120 mmHg，可急剧增加灌注大鼠心脏的功;在含葡萄糖或葡萄糖+乙酸盐的培养基灌注1分钟内，耗氧率和三羧酸循环周转率增加2.5倍，糖酵解率增加一倍，甘油三酯脂肪酸氧化显著增强。2.增加心脏作功对心脏磷酸肌酸、ATP、ADP和5 '-AMP浓度无明显影响。三羧酸循环中间产物的唯一显着变化是葡萄糖灌注中苹果酸的减少、乙酰辅酶A和柠檬酸盐的减少以及葡萄糖+醋酸盐灌注中天冬氨酸的增加。3.细胞内磷酸己糖、葡萄糖和糖原浓度的测量表明，通过激活磷酸果糖激酶和随后的己糖激酶，工作加速了糖酵解;这种激活不能被已知的磷酸果糖激酶效应物的变化所解释。4.在任一灌注压下的乙酸盐增加了乙酰辅酶A、柠檬酸盐、谷氨酸盐和苹果酸盐的心脏浓度，并降低了天冬氨酸盐的浓度;乙酸盐增加了50-60%的三羧酸循环周转率，并抑制了糖酵解和丙酮酸氧化。5.鉴于乙酸和心脏工作对循环中间体浓度的显著不同影响，伴随乙酸利用的变化可能与控制糖酵解和丙酮酸氧化的循环调节功能有关，而与循环周转率的相关增加无关。这表明，控制循环周转率的关键代谢物的浓度可能会随着每次心跳而波动，这可能解释了为什么在本研究中随着工作的增加没有检测到显著变化（例如腺嘌呤核苷酸浓度）。
1. The work of the perfused rat heart was acutely increased by raising the aortic pressure in the Langendorff preparation from 50 to 120mmHg; within 1 min in perfusions with media containing glucose or glucose+acetate, rates of oxygen consumption and tricarboxylate-cycle turnover increased 2.5-fold, glycolysis rate doubled and oxidation of triglyceride fatty acid was strikingly enhanced. 2. Increased cardiac work had no significant effects on the heart concentrations of creatine phosphate, ATP, ADP or 5'-AMP. The only significant changes in tricarboxylate-cycle intermediates were a decrease in malate in perfusions with glucose and decreases in acetyl-CoA and citrate and an increase in aspartate in perfusions with glucose+acetate. 3. Measurements of intracellular concentrations of hexose phosphates, glucose and glycogen indicated that work accelerated glycolysis by activation of phosphofructokinase and subsequently hexokinase; the activation could not be accounted for by changes in the known effectors of phosphofructokinase. 4. Acetate at either perfusion pressure increased heart concentrations of acetyl-CoA, citrate, glutamate and malate and decreased that of aspartate; acetate increased tricarboxylate-cycle turnover by 50-60% and inhibited glycolysis and pyruvate oxidation. 5. In view of the markedly different effects of acetate and of cardiac work on the concentrations of cycle intermediates the changes that accompany acetate utilization may be specifically concerned with the regulatory functions of the cycle in control of glycolysis and pyruvate oxidation and not with the associated increase in cycle turnover. It is suggested that the concentrations of key metabolites controlling the rate of cycle turnover may fluctuate with each heart beat and that this may explain why no significant changes (for example, in adenine nucleotide concentrations) have been detected with increased work in the present study.