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 con structed to fit the kinetics of skeletal muscle phosphofructokinase wi th respect to variations in AMP, ATP, fructose-6-P, and fructose 1,6-P -2 levels. A Monod-Wyman-Changeux model for a tetrameric enzyme is con sidered. However, it is found that the kinetic data fit considerably b etter with an assumption of identical, independent subunits. With para meters that fit these data and with a previous model for the rest of g lycolysis, product activation of phosphofructokinase leads to oscillat ions of glycolytic intermediates and [ATP] resembling those observed e xperimentally in muscle extracts. The period is several minutes. The m odel can also produce oscillations at neutral pH and with [ATP] repres entative of an intact cell. Under both conditions the mean concentrati ons and oscillations vary with the rate of glucose phosphorylation in a plausible manner only if some amount of glucose-6-phosphatase or glu cose-6-P dehydrogenase activity is assumed or if hexokinase is inhibit ed by glucose-6-P. Also, the model can be reduced to two variables for ease of analysis and the oscillation mechanism thereby illustrated.