Temporal organization of the phosphofructokinase/fructose-1,6-biphosphatase cycle.

The dynamic and functional organization of the fructose-6-phosphate/fructose-1,6-bisphosphate cycle has been investigated in an open and homogeneous reconstituted enzyme system containing phosphofructokinase, fructose-1,6-biphosphatase, pyruvate kinase, adenylate kinase and glucose 6-phosphate isomerase. The properties of this system were analyzed by a model based on the kinetic properties of the individual enzymes. It could be shown that in a broad parameter region sustained oscillations arise. At low maximum activities of phosphofructokinase a domain of multiple stationary states occurs, in which stable stationary states can coexist with a stable oscillatory or with an alternate stable stationary state. The occurrence of oscillations and the emergence of alternate stationary motions are caused mainly by the reciprocal effect of the allosteric effectors AMP and fructose-2,6-bisphosphatase must be involved in the reaction network. The study of bisphosphatase. The attained states can either be glycolytic or gluconeogenic, their metabolic efficiencies depend mainly on the maximum activities of phosphofructokinase and fructose-1,6-bisphosphatase as well as on the supply of fructose-6-phosphate and fructose-1,6-bisphosphate. Efficient metabolic states arise only when both the enzyme concentrations and the rates of substrate supply favor either the glycolytic or the gluconeogenic mode of action. At medium maximum concentrations of the enzymes oscillations occur, in which glycolytic and gluconeogenic states are consecutively passed. A high rate of substrate cycling is observed only at the transitions between the functionally antagonistic phases of the periodicities. By this temporal organization the mean efficiency of the states is increased. The integration of fructose-2,6-bisphosphate as very sensitively acting activator of phosphofructokinase and inhibitor of fructose-1,6-bisphosphatase gives rise either to emergence of oscillations or of their extinction. Generally, the glycolytic mode is favored by this effector because of its stimulatory action on the phosphofructokinase activity.