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

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 p...

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Main Authors: Johan H. van Heerden, Meike T. Wortel, Frank J. Bruggeman, Joseph J. Heijnen, Yves J.M. Bollen, Robert Planqué, Josephus Hulshof, Tom G. O’Toole, S. Aljoscha Wahl, Bas Teusink
Format: Article
Language:English
Published: Shared Science Publishers OG 2015-02-01
Series:Microbial Cell
Subjects:
Online Access:http://microbialcell.com/researcharticles/fatal-attraction-in-glycolysis-how-saccharomyces-cerevisiae-manages-sudden-transitions-to-high-glucose/
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author Johan H. van Heerden
Meike T. Wortel
Frank J. Bruggeman
Joseph J. Heijnen
Yves J.M. Bollen
Robert Planqué
Josephus Hulshof
Tom G. O’Toole
S. Aljoscha Wahl
Bas Teusink
author_facet Johan H. van Heerden
Meike T. Wortel
Frank J. Bruggeman
Joseph J. Heijnen
Yves J.M. Bollen
Robert Planqué
Josephus Hulshof
Tom G. O’Toole
S. Aljoscha Wahl
Bas Teusink
author_sort Johan H. van Heerden
collection DOAJ
description 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.]
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spelling doaj.art-dd2ccf032fec4f26af023e85a24c081a2025-03-12T13:46:42ZengShared Science Publishers OGMicrobial Cell2311-26382015-02-011310310610.15698/mic2014.01.133Fatal attraction in glycolysis: how Saccharomyces cerevisiae manages sudden transitions to high glucoseJohan H. van Heerden0Meike T. Wortel1Frank J. Bruggeman2Joseph J. Heijnen3Yves J.M. Bollen4Robert Planqué5Josephus Hulshof6Tom G. O’Toole7S. Aljoscha Wahl8Bas Teusink9Systems Bioinformatics/AIMMS/NISB, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.Systems Bioinformatics/AIMMS/NISB, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.Systems Bioinformatics/AIMMS/NISB, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.Department of Biotechnology, Delft University of Technology, Julianalaan 67, Delft 2628 BC, Netherlands.Department of Molecular Cell Biology, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.Department of Mathematics, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.Department of Mathematics, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands. Department of Molecular Cell Biology and Immunology, Vrije University Medical Center, v/d Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.Department of Biotechnology, Delft University of Technology, Julianalaan 67, Delft 2628 BC, Netherlands.Systems Bioinformatics/AIMMS/NISB, VU University, De Boelelaan 1085, 1081HV Amsterdam, The Netherlands.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.]http://microbialcell.com/researcharticles/fatal-attraction-in-glycolysis-how-saccharomyces-cerevisiae-manages-sudden-transitions-to-high-glucose/carbon metabolismglycolysisdynamic regulationmetabolic modelbistabilityheterogeneityyeast
spellingShingle Johan H. van Heerden
Meike T. Wortel
Frank J. Bruggeman
Joseph J. Heijnen
Yves J.M. Bollen
Robert Planqué
Josephus Hulshof
Tom G. O’Toole
S. Aljoscha Wahl
Bas Teusink
Fatal attraction in glycolysis: how Saccharomyces cerevisiae manages sudden transitions to high glucose
Microbial Cell
carbon metabolism
glycolysis
dynamic regulation
metabolic model
bistability
heterogeneity
yeast
title Fatal attraction in glycolysis: how Saccharomyces cerevisiae manages sudden transitions to high glucose
title_full Fatal attraction in glycolysis: how Saccharomyces cerevisiae manages sudden transitions to high glucose
title_fullStr Fatal attraction in glycolysis: how Saccharomyces cerevisiae manages sudden transitions to high glucose
title_full_unstemmed Fatal attraction in glycolysis: how Saccharomyces cerevisiae manages sudden transitions to high glucose
title_short Fatal attraction in glycolysis: how Saccharomyces cerevisiae manages sudden transitions to high glucose
title_sort fatal attraction in glycolysis how saccharomyces cerevisiae manages sudden transitions to high glucose
topic carbon metabolism
glycolysis
dynamic regulation
metabolic model
bistability
heterogeneity
yeast
url http://microbialcell.com/researcharticles/fatal-attraction-in-glycolysis-how-saccharomyces-cerevisiae-manages-sudden-transitions-to-high-glucose/
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