Understanding bistability in yeast glycolysis using general properties of metabolic pathways

• Published in: Mathematical biosciences Vol. 255; pp. 33 - 42
• Main Authors: Planqué, Robert, Bruggeman, Frank J., Teusink, Bas, Hulshof, Josephus
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2014
• Subjects: Adenosine Triphosphate - metabolism; Bifurcation analysis; Biochemical pathways; Differential equations; Energy Metabolism; Fructosediphosphates - metabolism; Glucosyltransferases - genetics; Glucosyltransferases - metabolism; Glycolysis; Mathematical Concepts; Metabolic Networks and Pathways; Models, Biological; Phosphates - metabolism; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - genetics; Saccharomyces cerevisiae Proteins - metabolism; Yeast; Glycolysis; Yeast; Biochemical pathways; Bifurcation analysis; Differential equations
• ISSN: 0025-5564; 1879-3134
• DOI: 10.1016/j.mbs.2014.06.006

•We study analytically all known behaviours of glycolysis in one core model.•The core model is based on a well-established model of yeast glycolysis.•We focus on on bistability between regular and so-called imbalanced states.•Techniques are widely applicable to biochemical pathways in general. Glycolysis is the central pathway in energy metabolism in the majority of organisms. In a recent paper, van Heerden et al. [1] showed experimentally and computationally that glycolysis can exist in two states, a global steady state and a so-called imbalanced state. In the imbalanced state, intermediary metabolites accumulate at low levels of ATP and inorganic phosphate. It was shown that Baker’s yeast uses a peculiar regulatory mechanism—via trehalose metabolism—to ensure that most yeast cells reach the steady state and not the imbalanced state. Here we explore the apparent bistable behaviour in a core model of glycolysis that is based on a well-established detailed model, and study in great detail the bifurcation behaviour of solutions, without using any numerical information on parameter values. We uncover a rich suite of solutions, including so-called imbalanced states, bistability, and oscillatory behaviour. The techniques employed are generic, directly suitable for a wide class of biochemical pathways, and could lead to better analytical treatments of more detailed models.