Co-ordinate control of phosphofructokinase and pyruvate kinase by fructose diphosphate: A mechanism for amplification and step changes in the regulation of glycolysis in liver

Abstract

Activation of both phosphofructokinase and pyruvate kinase by fructose diphosphate in liver provides a means of amplifying effects of other activators or inhibitors in controlling the rate of glycolysis. Two types of behavior can occur, depending on the choice of affinity constants of the two enzymes for fructose diphosphate in a simple model: (i) there may be a steady state corresponding to each value of the fructose diphosphate concentration, so that the glycolytic rate is continuously variable, or (ii) there may be two (or more) regions of stable steady states, separated by a zone of instability, so that the system shifts abruptly between low and high glycolytic rates at critical concentrations of fructose diphosphate. A low glycolytic rate corresponds to net gluconeogenesis when the gluconeogenic enzymes are included. Calculations from data from perfused liver support the proposal that the free fructose diphosphate concentration is a major factor controlling glycolysis in liver and amplifying the effect of changes in the fructose 6-phosphate concentration which occur in response to variation in the glucose concentration.