A model for glycolytic oscillations based on skeletal muscle phosphofructokinase kinetics

Existing models for glycolytic oscillations are not based on detailed experimental kinetics of the glycolytic enzymes. Here, a model is constructed to fit the kinetics of skeletal muscle phosphofructokinase with respect to variations in AMP, ATP, fructose-6-P, and fructose 1,6-P2 levels. A Monod-Wyman-Changeux model for a tetrameric enzyme is considered. However, it is found that the kinetic data fit considerably better with an assumption of identical, independent subunits. With parameters that fit these data and with a previous model for the rest of glycolysis, product activation of phosphofructokinase leads to oscillations of glycolytic intermediates and [ATP] resembling those observed experimentally in muscle extracts. The period is several minutes. The model can also produce oscillations at neutral pH and with [ATP] representative of an intact cell. Under both conditions the mean concentrations and oscillations vary with the rate of glucose phosphorylation in a plausible manner only if some amount of glucose-6-phosphatase or glucose-6-P dehydrogenase activity is assumed or if hexokinase is inhibited by glucose-6-P. Also, the model can be reduced to two variables for ease of analysis and the oscillation mechanism thereby illustrated.