title: Fatal attraction in glycolysis: howSaccharomyces cerevisiaemanages sudden transitions to high glucose.
abstract: In the model eukaryoteSaccharomyces 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 animbalanced 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 exhibitstwodynamic 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 Piavailability under dynamic conditions. [van Heerdenet al.Science (2014), DOI: 10.1126/science.1245114.].
authors.affiliation: 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.
authors.forename: Johan H V
authors.initials: JH
authors.lastname: Heerden
authors.affiliation: 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.
authors.forename: Meike T
authors.initials: MT
authors.lastname: Wortel
authors.affiliation: 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.
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Bruggeman
authors.affiliation: 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.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Heijnen
authors.affiliation: 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.
authors.forename: Yves J
authors.initials: YJ
authors.lastname: Bollen
authors.affiliation: Department of Mathematics, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Planqué
authors.affiliation: Department of Mathematics, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.
authors.forename: Josephus
authors.initials: J
authors.lastname: Hulshof
authors.affiliation: Department of Molecular Cell Biology and Immunology, Vrije University Medical Center, v/d Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
authors.forename: Tom G
authors.initials: TG
authors.lastname: O'Toole
authors.affiliation: 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.
authors.forename: S A
authors.initials: SA
authors.lastname: Wahl
authors.affiliation: 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.
authors.forename: Bas
authors.initials: B
authors.lastname: Teusink
keywords: bistability; carbon metabolism; dynamic regulation; glycolysis; heterogeneity; metabolic model; yeast