Pareto Optimality Explanation of the Glycolytic Alternatives in Nature

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number2633
JournalScientific reports
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2019

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Adenosine Triphosphate
Costs and Cost Analysis
Glycolysis
Adenosine Diphosphate
Proteins
Pyruvic Acid
Thermodynamics
Glucose
Enzymes

All Science Journal Classification (ASJC) codes

  • General

Cite this

Ng, Chiam Yu ; Wang, Lin ; Chowdhury, Anupam ; Maranas, Costas D. / Pareto Optimality Explanation of the Glycolytic Alternatives in Nature. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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Pareto Optimality Explanation of the Glycolytic Alternatives in Nature. / Ng, Chiam Yu; Wang, Lin; Chowdhury, Anupam; Maranas, Costas D.

In: Scientific reports, Vol. 9, No. 1, 2633, 01.12.2019.

Research output: Contribution to journalArticle

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