Chalmers Conferences, 9th European Conference on Mathematical and Theoretical Biology

Understanding bistability in yeast glycolysis using general properties of metabolic pathways
Bob Planqué

Last modified: 2014-03-31


Trehalose biosynthesis is a side branch in the glycolytic pathways in many organisms. It has been known for a long time that knocking out this function deprives yeast cells to grow on excess glucose. Instead, intermediate metabolites keep accumulating, at the expense of inorganic phosphate and ATP production. In a recent paper in Science, Van Heerden et al. [1] showed, using a combination of numerical and experimental studies, that trehalose biosynthesis acts as a rescue mechanism. Intermediate metabolite concentrations are steered towards normal values, so that the `imbalanced state' is avoided. Surprisingly, both in the knock-out and wild type cells, bistability may be found between regular steady states and imbalanced states. Here, we explore this bistability in a core model of glycolysis that is based on a well-established detailed model by Teusink et al [2]. We study in great detail the occurrence of regular and imbalanced states, bistability between the two, and also oscillatory behaviour. The techniques we employ are not taylored to the specific situation, but use generic properties of metabolic pathways. We will discuss to what extent these allow larger and more detailed metabolic networks to be studied analytically.

[1] Van Heerden, et al. Lost in transition: uncontrolled startup of glycolysis results in subpopulations of non-growing cells. 2014. Science. DOI:10.1126/science.1245114

[2] Teusink et al. Can yeast glycolysis be understood in terms of in vitro kinetics of constituent enzymes? Testing biochemistry. Eur. J. Biochem. 2000 267:5313-5329.


systems biology; metabolic pathways; differential equations; yeast; bifurcation analysis