Pareto Optimality Explanation of the Glycolytic Alternatives in Nature

Ng, Chiam Yu; Wang, Lin; Chowdhury, Anupam; Maranas, Costas D.

doi:10.1038/s41598-019-38836-9

Title: Pareto Optimality Explanation of the Glycolytic Alternatives in Nature

Journal Article · Fri Feb 22 00:00:00 EST 2019 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-019-38836-9· OSTI ID:1624453

Ng, Chiam Yu ^[1]; Wang, Lin ^[1]; Chowdhury, Anupam ^[1];

^[1]

Pennsylvania State Univ., University Park, PA (United States)

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.

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Research Organization:: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER); National Science Foundation (NSF)

Grant/Contract Number:: AC05-00OR22725; EEC-0813570

OSTI ID:: 1624453

Journal Information:: Scientific Reports, Vol. 9, Issue 1; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cited by: 10 works

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