Robustness of glycolysis in yeast to internal and external noise

Glycolysis is one of the most essential intracellular networks, found in a wide range of organisms. Due to its importance and due to its wide industrial applications, many experimental studies on all details of this process have been performed. Until now, however, to the best of our knowledge, there has been no comprehensive investigation of the robustness of this important process with respect to internal and external noise. To close this gap, we applied two complementary and mutually supporting approaches to a full-scale model of glycolysis in yeast: (a) a linear stability analysis based on a generalized modeling that deals only with those effective parameters of the system that are relevant for its stability, and (b) a numerical integration of the rate equations in the presence of noise, which accounts for imperfect mixing. The results suggest that the occurrence of metabolite oscillations in part of the parameter space is a side effect of the optimization of the system for maintaining a constant adenosine triphosphate level in the face of a varying energy demand and of fluctuations in the parameters and metabolite concentrations.