Interrelations between glycolysis and the hexose monophosphate shunt in erythrocytes as studied on the basis of a mathematical model.

A mathematical model is presented which comprises the reactions of glycolysis, the hexose monophosphate shunt (HMS) and the glutathione system in erythrocytes. The model is used to calculate stationary and time-dependent metabolic states of the cell in vitro and in vivo. The model properly accounts for the following metabolic features observed in vitro: (a) stimulation of the oxidative pentose pathway after addition of pyruvate due to a NADP-dependent lactate dehydrogenase as coupling enzyme between glycolysis and the oxidative pentose pathway, (b) relative share of the oxidative pentose pathway in the total consumption of glucose amounting to approximately 10% in the normal case and to approximately 90% under conditions of oxidative stress excreted by methylene blue. From the application of the model to in vivo conditions it is predicted that (c) under normal conditions glycolysis and the HMS are independently regulated by the energetic and oxidative load, respectively, (d) under conditions of enhanced energetic or oxidative load both glycolysis and the HMS are mainly controlled by the hexokinase; in this situation the highest possible values of the energetic and oxidative load which are compatible with cell integrity are strongly coupled and considerably restricted in comparison with the normal case, (e) the stationary states possess bifurcation points at high and low values of the energetic load.