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 ki nase, adenylate kinase and glucose g-phosphate isomerase cooperate to a multienzyme system centered around the 6-phosphofructokinase (6-PFK) and fructose 1,6-bisphosphatase (FBPase) cycle. The reaction system o perates under thermodynamically open conditions maintained by a contin uous supply of substrates, i.e., glucose 6-phosphate (Glc6P), ATP and phosphoenolpyruvate (PPrv) in a flow-through reaction chamber. Appropr iate conditions lead to the occurence of (two) coexisting and markedly different time-independent states in the metabolite concentrations an d fluxes. For particular experimental conditions, changes in the influ x adenylic energy charge, [AEC](IN), may cause transitions between the se 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 hom artific ial or non-realistic experimental constraints, but are a potential int rinsic property of any non-linear dynamic system exhibiting bi- or mul tistability. These one-way transitions may well have important biologi cal implications with respect to switching, adaptation and memory phen omena. (C) 1997 Academic Press.