Modulation by citrate of glycolytic oscillations in skeletal muscle extracts

Oscillatory behavior of glycolysis in cell-free extracts of skeletal muscle involves repeated bursts of phosphofructokinase activity and associated oscillations in the [ATP]/[ADP] ratio. Addition of citrate, a potent physiological inhibitor of phosphofructokinase, decreased the frequency of the oscillations and delayed the first burst of phosphofructokinase activity in a dose-dependent manner. Citrate decreased the trigger point [ATP]/[ADP] ratio at which bursts of phosphofructokinase activity were initiated but had a much smaller effect on the average [ATP]/[ADP] ratio and did not decrease the peak values of the ratio. When oscillations were prevented by addition of fructose-2,6-P2, the decrease in the [ATP]/[ADP] ratio caused by citrate in the steady state system was similar to the decrease in the trigger point [ATP]/[ADP] ratio in the oscillatory system. The decrease in the average [ATP]/[ADP] ratio was greater in the steady state system than in the oscillating system. These results demonstrate advantages of oscillatory behavior of glycolysis in the regulation of carbohydrate utilization and the maintenance of a high [ATP]/[ADP] ratio.