ArticleScientific reports2019
Pareto Optimality Explanation of the Glycolytic Alternatives in Nature.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Microbial Metabolism: Primary and Secondary Metabolites.Progress in molecular and subcellular biology · 2026Review
- Article
- Plastid ancestors lacked a complete Entner-Doudoroff pathway, limiting plants to glycolysis and the pentose phosphate pathway.Nature communications · 2024Article
- Mathematical reconstruction of the metabolic network in an in-vitro multiple myeloma model.PLoS computational biology · 2023Article
- Metabolic Determinants of Cardiomyocyte Proliferation.Stem cells (Dayton, Ohio) · 2022Article
- Functional Analysis of HApplied and environmental microbiology · 2022Article
- Activating Silent Glycolysis Bypasses inBiodesign research · 2022Article
- dGPredictor: Automated fragmentation method for metabolic reaction free energy prediction and de novo pathway design.PLoS computational biology · 2021Article
- Proteome Regulation Patterns Determine Escherichia coli Wild-Type and Mutant Phenotypes.mSystems · 2021Article
- Poly-aneuploid cancer cells promote evolvability, generating lethal cancer.Evolutionary applications · 2020Article
- Article
- Redox controls metabolic robustness in the gas-fermenting acetogenProceedings of the National Academy of Sciences of the United States of America · 2020Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
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.
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