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Data-driven model of glycolysis identifies the role of allostery in maintaining ATP homeostasis

Mangyu Choe, Tal Einav, Rob Phillips, View ORCID ProfileDenis V. Titov
doi: https://doi.org/10.1101/2022.12.28.522046
Mangyu Choe
1Department of Nutritional Sciences and Toxicology, University of California; Berkeley, CA 94720, USA
2Department of Molecular and Cell Biology, University of California; Berkeley, CA 94720, USA
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Tal Einav
4Division of Biology and Biological Engineering, California Institute of Technology; Pasadena, CA 91125, USA
6Basic Sciences Division and Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA
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Rob Phillips
4Division of Biology and Biological Engineering, California Institute of Technology; Pasadena, CA 91125, USA
5Department of Physics, California Institute of Technology; Pasadena, CA 91125, USA
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Denis V. Titov
1Department of Nutritional Sciences and Toxicology, University of California; Berkeley, CA 94720, USA
2Department of Molecular and Cell Biology, University of California; Berkeley, CA 94720, USA
3Center for Computational Biology, University of California; Berkeley, CA 94720, USA
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  • ORCID record for Denis V. Titov
  • For correspondence: titov@berkeley.edu
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Abstract

The specific roles of allostery in regulating metabolism are not well understood. Here, we develop a data-driven mathematical model of mammalian glycolysis that uses enzyme rate equations and coupled ordinary differential equations. The key components of our model are the rate equations for allosterically regulated enzymes based on the Monod-Wyman-Changeux model that we derive using a rigorous analysis of thousands of in vitro kinetic measurements. The resulting model recapitulates the properties of glycolysis observed in live cells and shows that the specific function of allosteric regulation is to maintain high and stable concentrations of ATP, while glycolysis without allosteric regulation is fully capable of producing ATP and ensuring that ATP hydrolysis generates energy. Our data-based modeling approach provides a roadmap for a better understanding of the role of allostery in metabolism regulation.

One-Sentence Summary The glycolysis model based on allosteric enzyme rate equations recapitulates properties of glycolysis observed in live cells.

Competing Interest Statement

The authors have declared no competing interest.

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  • Updated to permissive distribution license and updated acknowledgments

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted December 30, 2022.
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Data-driven model of glycolysis identifies the role of allostery in maintaining ATP homeostasis
Mangyu Choe, Tal Einav, Rob Phillips, Denis V. Titov
bioRxiv 2022.12.28.522046; doi: https://doi.org/10.1101/2022.12.28.522046
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Data-driven model of glycolysis identifies the role of allostery in maintaining ATP homeostasis
Mangyu Choe, Tal Einav, Rob Phillips, Denis V. Titov
bioRxiv 2022.12.28.522046; doi: https://doi.org/10.1101/2022.12.28.522046

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