Fructose 2,6-bisphosphate induces irreversible transitions in cell-free extracts of rat liver

The effect of fructose 2,6-bisphosphate on the dynamics of the 6-phosphofructo-1-kinase/fructose-1,6-bisphos-phatase cycle is investigated in a cell-free extract of rat liver under steady-state conditions. Bistability emerges on the basis of the reciprocal allosteric modulation of 6-phosphofructo-1-kinase and fructose-1,6-bisphosphatase. Under conditions of bistability fructose 2,6-bisphosphate may cause transitions between alternative steady states. However, in contrast to what is frequently observed in bistable systems, within a broad range of experimental conditions these transitions proceed irreversibly from states with high ATP to states characterized by low ATP.