Control of maximum rates of glycolysis in rat cardiac muscle.

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Abstract
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.