Irreversible metabolic transitions: the glucose 6-phosphate metabolism in yeast cell-free extracts

The steady-state and dynamic behavior of a partial glycolytic reaction sequence are investigated in cell-free extracts of yeast. Pyruvate kinase, adenylate kinase and glucose 6-phosphate isomerase cooperate to a multienzyme system centered around the 6-phosphofructokinase (6-PFK) and fructose 1,6-bisphosphatase (FBPase) cycle. The reaction system operates under thermodynamically open conditions maintained by a continuous supply of substrates, i.e., glucose 6-phosphate (Glc6P), ATP and phosphoenolpyruvate (PPrv) in a flow-through reaction chamber. Appropriate conditions lead to the occurrence of (two) coexisting and markedly different time-independent states in the metabolite concentrations and fluxes. For particular experimental conditions, changes in the influx adenylic energy charge, [AEC]IN, may cause transitions between these alternative steady states which are either reversible as it occurs in classical hysteresis phenomena, or, more importantly, irreversible (irreversible transitions, IT) where the system is not able to switch back to its previous state even when the perturbation is reverted. The emergence of these irreversible transitions do not result from artificial or non-realistic experimental constraints, but are a potential intrinsic property of any non-linear dynamic system exhibiting bi- or multistability. These one-way transitions may well have important biological implications with respect to switching, adaptation and memory phenomena.