title: Understanding bistability in yeast glycolysis using general properties of metabolic pathways.
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.
  
  
  CONCLUSIONS
  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.
authors: Department of Mathematics, VU University Amsterdam, De Boelelaan 1081, 1081 HV Amsterdam, The Netherlands. Electronic address: r.planque@vu.nl.
authors: Robert
authors: R
authors: Planqué
authors: Molecular Cell Physiology, Netherlands Institute of Systems Biology, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.
authors: Frank J
authors: FJ
authors: Bruggeman
authors: Molecular Cell Physiology, Netherlands Institute of Systems Biology, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.
authors: Bas
authors: B
authors: Teusink
authors: Department of Mathematics, VU University Amsterdam, De Boelelaan 1081, 1081 HV Amsterdam, The Netherlands.
authors: Josephus
authors: J
authors: Hulshof
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D004734:Energy Metabolism; D005635:Fructosediphosphates / Q000378:metabolism; D005964:Glucosyltransferases / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis; D055641:Mathematical Concepts; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D010710:Phosphates / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D005635:Fructosediphosphates; D010710:Phosphates; D029701:Saccharomyces cerevisiae Proteins; D000255:Adenosine Triphosphate; D005964:Glucosyltransferases; C023180:trehalose-6-phosphate synthase; C029063:fructose-1,6-diphosphate
keywords: Bifurcation analysis; Biochemical pathways; Differential equations; Glycolysis; Yeast