CONTROL OF MAXIMUM RATES OF GLYCOLYSIS IN RAT CARDIAC-MUSCLE

The maximum rate of glucose utilization by isolated rat hearts was approximately 16 μmol/g dry weight per minute. This rate was observed in aerobic hearts that were developing high levels of ventricular pressure. This same rate has been reported for anoxic hearts. In both conditions, stimulation of glycolysis resulted in increased cytosolic NADH/NAD ratios and the rate of disposal of glycolytically produced NADH appeared to limit the maximum glycolytic rate. In aerobic hearts, oxidation of glucose and lactate increased linearly as developed ventricular pressure was raised from 60 to 150 mm Hg, but then plateaued. Oxygen consumption and pyruvate oxidation, on the other hand, continued to increase linearly over a wide range of cardiac work. The observation that substrates that produce NADH in the cytosol (glycose and lactate) showed limited rates of utilization, whereas pyruvate oxidation was linearly related to oxygen consumption, indicates that disposal of cytosolic NADH limits maximum stimulation of glycolysis. With maximum stimulation, the rate of glyceraldehyde-3-phosphate dehydrogenase appeared to determine the overall rate of the glycolytic pathway. The rate of this enzyme was probably restricted by an increased cytosolic NADH/NAD ratio. Glycolytic production of pyruvate was not fast enough to match the rate of its utilization 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 more than 7% of the normal aerobic requirements for energy. It is concluded that glycolytic rate in cardiac muscle is not sufficient to support high rates of oxidative metabolism.