CONTROL OF MAXIMUM RATES OF GLYCOLYSIS IN RAT CARDIAC-MUSCLE

CONTROL OF MAXIMUM RATES OF GLYCOLYSIS IN RAT CARDIAC-MUSCLE
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DOI:
10.1161/01.res.44.2.166
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发表时间:
1979-01-01
影响因子:
20.1
通讯作者:
NEELY, JR
NEELY, JR
中科院分区:
医学1区
文献类型:
--
作者:
KOBAYASHI, K;NEELY, JR

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离体大鼠心脏对葡萄糖的最大利用率约为16.mu。mol/g干重量每分钟。这一速度在有氧心脏中观察到高水平的心室压。据报道,缺氧心脏也有同样的比率。在这两种情况下,糖酵解的刺激导致细胞质内NADH/NAD比值的增加,并且糖酵解产生的NADH的处理速率似乎限制了最大糖酵解速率。在有氧心脏中,葡萄糖和乳酸氧化随着心室压从60-150 mm Hg升高而线性增加,但随后趋于平稳。在大范围的心脏工作中,氧气消耗和丙酮酸氧化继续呈线性增加。胞质内产生NADH的底物(葡萄糖和乳酸)利用率有限,丙酮酸氧化与氧气消耗呈线性关系,表明胞质内NADH的处理限制了糖酵解的最大刺激。在最大刺激下,甘油醛-3-磷酸脱氢酶反应的速率似乎决定了糖酵解途径的总体速率。这种酶的速率可能受到细胞质内NADH/NAD比值增加的限制。在研究的任何条件下,丙酮酸的糖酵解生产速度都不足以与柠檬酸循环的利用率相匹配,并且由于葡萄糖是唯一的外源底物,柠檬酸的合成受到乙酰辅酶a可用性的限制。糖酵解产生的厌氧ATP从未占正常有氧能量需求的7%。心肌的糖酵解速率不足以支持高的氧化代谢速率。
The maximum rate of glucose utilization by isolated rat hearts was approximately 16 .mu.mol/g dry wt per min. This rate was observed in aerobic hearts developing high levels of ventricular pressure. This same rate was reported for anoxic hearts. In both conditions, stimulation of glycolysis resulted in increased cytosolic NADH/NAD ratios and rate of disposal of glycolytically produced NADH appeared to limit maximum glycolytic rate. In aerobic hearts, glucose and lactate oxidation increased linearly as developed ventricular pressure raised from 60-150 mm Hg, but then plateaued. O2 consumption and pyruvate oxidation continued to increase linearly over a wide range of cardiac work. Substrates that produce NADH in the cytosol (glucose and lactate) showed limited rates of utilization and pyruvate oxidation was linearly related to O2 consumption, indicating that disposal of cytosolic NADH limits maximum stimulation of glycolysis. With maximum stimulation, the rate of glyceraldehyde-3-phosphate dehydrogenase reaction appeared to determine the overall rate of the glycolytic pathway. The rate of this enzyme was probably restricted by increased cytosolic NADH/NAD ratio. Glycolytic production of pyruvate was not fast enough to match its utilization rate by the citric acid cycle under any condition studied, and with glucose as the only exogenous substrate, synthesis of citrate was limited by availability of acetyl-CoA. Anaerobic production of ATP from glycolysis never accounted for > 7% of the normal aerobic energy requirements. Glycolytic rate in cardiac muscle is not sufficient to support high rates of oxidative metabolism.