Understanding bistability in yeast glycolysis using general properties of metabolic pathways

Math Biosci. 2014 Sep;255:33-42. doi: 10.1016/j.mbs.2014.06.006. Epub 2014 Jun 21.

Abstract

Glycolysis is the central pathway in energy metabolism in the majority of organisms. In a recent paper, van Heerden et al. 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.

Results: 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.

Conclusion: 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.

Keywords: Bifurcation analysis; Biochemical pathways; Differential equations; Glycolysis; Yeast.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • 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

Substances

  • Fructosediphosphates
  • Phosphates
  • Saccharomyces cerevisiae Proteins
  • Adenosine Triphosphate
  • Glucosyltransferases
  • trehalose-6-phosphate synthase
  • fructose-1,6-diphosphate