Understanding bistability in yeast glycolysis using general properties of metabolic pathways.

Robert Planqué, Frank J Bruggeman, Bas Teusink, Josephus Hulshof

Journal: Mathematical biosciences 2015;255():33-42

PMID: 24956444

Abstract

UNLABELLED

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.

Copyright © 2014 Elsevier Inc. All rights reserved.

Address: Department of Mathematics, VU University Amsterdam, De Boelelaan 1081, 1081 HV Amsterdam, The Netherlands. Electronic address: [email protected].; Molecular Cell Physiology, Netherlands Institute of Systems Biology, VU University Amsterdam, De Boelelaan 1085, 1081 HV Amsterdam, The Netherlands.; Department of Mathematics, VU University Amsterdam, De Boelelaan 1081, 1081 HV Amsterdam, The Netherlands.

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