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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Shared Science Publishers OG
2015-02-01
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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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language | English |
last_indexed | 2025-03-14T01:45:18Z |
publishDate | 2015-02-01 |
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series | Microbial Cell |
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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