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Microb Cell. 2014 Feb 20;1(3):103-106. doi: 10.15698/mic2014.01.133.

Fatal attraction in glycolysis: how Saccharomyces cerevisiae manages sudden transitions to high glucose.

Author information

1
Systems Bioinformatics/AIMMS/NISB, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands. ; Kluyver Centre for Genomics of Industrial Fermentation/NCSB, Delft University of Technology, Julianalaan 67, Delft 2628 BC, The Netherlands. ; Department of Molecular Cell Biology, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.
2
Systems Bioinformatics/AIMMS/NISB, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands. ; Department of Molecular Cell Biology, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.
3
Department of Biotechnology, Delft University of Technology, Julianalaan 67, Delft 2628 BC, Netherlands. ; Kluyver Centre for Genomics of Industrial Fermentation/NCSB, Delft University of Technology, Julianalaan 67, Delft 2628 BC, The Netherlands.
4
Department of Molecular Cell Biology, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands. ; LaserLaB Amsterdam, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.
5
Department of Mathematics, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.
6
Department of Molecular Cell Biology and Immunology, Vrije University Medical Center, v/d Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.

Abstract

In the model eukaryote Saccharomyces cerevisiae, it has long been known that a functional trehalose pathway is indispensable for transitions to high glucose conditions. Upon addition of glucose, cells with a defect in trehalose 6-phosphate synthase (Tps1), the first committed step in the trehalose pathway, display what we have termed an imbalanced glycolytic state; in this state the flux through the upper part of glycolysis outpaces that through the lower part of glycolysis. As a consequence, the intermediate fructose 1,6-bisphosphate (FBP) accumulates at low concentrations of ATP and inorganic phosphate (Pi). Despite significant research efforts, a satisfactory understanding of the regulatory role that trehalose metabolism plays during such transitions has remained infamously unresolved. In a recent study, we demonstrate that the startup of glycolysis exhibits two dynamic fates: a proper, functional, steady state or the imbalanced state described above. Both states are stable, attracting states, and the probability distribution of initial states determines the fate of a yeast cell exposed to glucose. Trehalose metabolism steers the dynamics of glycolysis towards the proper functional state through its ATP hydrolysis activity; a mechanism that ensures that the demand and supply of ATP is balanced with Pi availability under dynamic conditions. [van Heerden et al. Science (2014), DOI: 10.1126/science.1245114.].

KEYWORDS:

bistability; carbon metabolism; dynamic regulation; glycolysis; heterogeneity; metabolic model; yeast

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