LAPSE:2018.0355
Published Article
LAPSE:2018.0355
Prediction of Metabolite Concentrations, Rate Constants and Post-Translational Regulation Using Maximum Entropy-Based Simulations with Application to Central Metabolism of Neurospora crassa
William R. Cannon, Jeremy D. Zucker, Douglas J. Baxter, Neeraj Kumar, Scott E. Baker, Jennifer M. Hurley, Jay C. Dunlap
July 31, 2018
We report the application of a recently proposed approach for modeling biological systems using a maximum entropy production rate principle in lieu of having in vivo rate constants. The method is applied in four steps: (1) a new ordinary differential equation (ODE) based optimization approach based on Marcelin’s 1910 mass action equation is used to obtain the maximum entropy distribution; (2) the predicted metabolite concentrations are compared to those generally expected from experiments using a loss function from which post-translational regulation of enzymes is inferred; (3) the system is re-optimized with the inferred regulation from which rate constants are determined from the metabolite concentrations and reaction fluxes; and finally (4) a full ODE-based, mass action simulation with rate parameters and allosteric regulation is obtained. From the last step, the power characteristics and resistance of each reaction can be determined. The method is applied to the central metabolism of Neurospora crassa and the flow of material through the three competing pathways of upper glycolysis, the non-oxidative pentose phosphate pathway, and the oxidative pentose phosphate pathway are evaluated as a function of the NADP/NADPH ratio. It is predicted that regulation of phosphofructokinase (PFK) and flow through the pentose phosphate pathway are essential for preventing an extreme level of fructose 1,6-bisphophate accumulation. Such an extreme level of fructose 1,6-bisphophate would otherwise result in a glassy cytoplasm with limited diffusion, dramatically decreasing the entropy and energy production rate and, consequently, biological competitiveness.
Keywords
mass action kinetics, maximum entropy production, metabolism, statistical thermodynamics
Subject
Suggested Citation
Cannon WR, Zucker JD, Baxter DJ, Kumar N, Baker SE, Hurley JM, Dunlap JC. Prediction of Metabolite Concentrations, Rate Constants and Post-Translational Regulation Using Maximum Entropy-Based Simulations with Application to Central Metabolism of Neurospora crassa. (2018). LAPSE:2018.0355
Author Affiliations
Cannon WR: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA
Zucker JD: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA [ORCID]
Baxter DJ: Research Computing Group, Pacific Northwest National Laboratory, Richland, WA 99352, USA
Kumar N: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99352, USA [ORCID]
Baker SE: Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99352, USA [ORCID]
Hurley JM: Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY 12180, USA
Dunlap JC: Department of Molecular and Systems Biology, Geisel School of Medicine at Dartmouth, Hanover, NH 03755, USA
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Journal Name
Processes
Volume
6
Issue
6
Article Number
E63
Year
2018
Publication Date
2018-05-28
Published Version
ISSN
2227-9717
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Original Submission
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PII: pr6060063, Publication Type: Journal Article
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LAPSE:2018.0355
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doi:10.3390/pr6060063
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Jul 31, 2018
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