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Title: Pareto Optimality Explanation of the Glycolytic Alternatives in Nature

Abstract

The Entner-Doudoroff (ED) and Embden-Meyerhof-Parnas (EMP) glycolytic pathways are largely conserved across glycolytic species in nature. Is this a coincidence, convergent evolution or there exists a driving force towards either of the two pathway designs? We addressed this question by first employing a variant of the optStoic algorithm to exhaustively identify over 11,916 possible routes between glucose and pyruvate at different pre-determined stoichiometric yields of ATP. Subsequently, we analyzed the thermodynamic feasibility of all the pathways at physiological metabolite concentrations and quantified the protein cost of the feasible solutions. Pareto optimality analysis between energy efficiency and protein cost reveals that the naturally evolved ED and EMP pathways are indeed among the most protein cost-efficient pathways in their respective ATP yield categories and remain thermodynamically feasible across a wide range of ATP/ADP ratios and pathway intermediate metabolite concentration ranges. In contrast, pathways with higher ATP yield (>2) while feasible, are bound within stringent and often extreme operability ranges of cofactor and intermediate metabolite concentrations. The preponderance of EMP and ED is thus consistent with not only optimally balancing energy yield vs. enzyme cost but also with ensuring operability for wide metabolite concentration ranges and ATP/ADP ratios.

Authors:
 [1];  [1];  [1]; ORCiD logo [1]
  1. Pennsylvania State Univ., University Park, PA (United States)
Publication Date:
Research Org.:
Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Science Foundation (NSF)
OSTI Identifier:
1624453
Grant/Contract Number:  
AC05-00OR22725; EEC-0813570
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY; science & technology; computational models; computer modelling; metabolic pathways

Citation Formats

Ng, Chiam Yu, Wang, Lin, Chowdhury, Anupam, and Maranas, Costas D. Pareto Optimality Explanation of the Glycolytic Alternatives in Nature. United States: N. p., 2019. Web. doi:10.1038/s41598-019-38836-9.
Ng, Chiam Yu, Wang, Lin, Chowdhury, Anupam, & Maranas, Costas D. Pareto Optimality Explanation of the Glycolytic Alternatives in Nature. United States. https://doi.org/10.1038/s41598-019-38836-9
Ng, Chiam Yu, Wang, Lin, Chowdhury, Anupam, and Maranas, Costas D. Fri . "Pareto Optimality Explanation of the Glycolytic Alternatives in Nature". United States. https://doi.org/10.1038/s41598-019-38836-9. https://www.osti.gov/servlets/purl/1624453.
@article{osti_1624453,
title = {Pareto Optimality Explanation of the Glycolytic Alternatives in Nature},
author = {Ng, Chiam Yu and Wang, Lin and Chowdhury, Anupam and Maranas, Costas D.},
abstractNote = {The Entner-Doudoroff (ED) and Embden-Meyerhof-Parnas (EMP) glycolytic pathways are largely conserved across glycolytic species in nature. Is this a coincidence, convergent evolution or there exists a driving force towards either of the two pathway designs? We addressed this question by first employing a variant of the optStoic algorithm to exhaustively identify over 11,916 possible routes between glucose and pyruvate at different pre-determined stoichiometric yields of ATP. Subsequently, we analyzed the thermodynamic feasibility of all the pathways at physiological metabolite concentrations and quantified the protein cost of the feasible solutions. Pareto optimality analysis between energy efficiency and protein cost reveals that the naturally evolved ED and EMP pathways are indeed among the most protein cost-efficient pathways in their respective ATP yield categories and remain thermodynamically feasible across a wide range of ATP/ADP ratios and pathway intermediate metabolite concentration ranges. In contrast, pathways with higher ATP yield (>2) while feasible, are bound within stringent and often extreme operability ranges of cofactor and intermediate metabolite concentrations. The preponderance of EMP and ED is thus consistent with not only optimally balancing energy yield vs. enzyme cost but also with ensuring operability for wide metabolite concentration ranges and ATP/ADP ratios.},
doi = {10.1038/s41598-019-38836-9},
journal = {Scientific Reports},
number = 1,
volume = 9,
place = {United States},
year = {Fri Feb 22 00:00:00 EST 2019},
month = {Fri Feb 22 00:00:00 EST 2019}
}

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Pathway Thermodynamics Highlights Kinetic Obstacles in Central Metabolism
journal, February 2014


Group Contribution Method for Thermodynamic Analysis of Complex Metabolic Networks
journal, August 2008

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The Protein Cost of Metabolic Fluxes
text, January 2016


Lower glycolysis carries a higher flux than any biochemically possible alternative
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