Glycolytic strategy as a tradeoff between energy yield and protein cost
Open accessAbstract
Contrary to the textbook portrayal of glycolysis as a single pathway conserved across all domains of life, not all sugar-consuming organisms use the canonical Embden-Meyerhoff-Parnass (EMP) glycolytic pathway. Prokaryotic glucose metabolism is particularly diverse, including several alternative glycolytic pathways, the most common of which is the Entner-Doudoroff (ED) pathway. The prevalence of the ED pathway is puzzling as it produces only one ATP per glucose--half as much as the EMP pathway. We argue that the diversity of prokaryotic glucose metabolism may reflect a tradeoff between a pathway's energy (ATP) yield and the amount of enzymatic protein required to catalyze pathway flux. We introduce methods for analyzing pathways in terms of thermodynamics and kinetics and show that the ED pathway is expected to require several-fold less enzymatic protein to achieve the same glucose conversion rate as the EMP pathway. Through genomic analysis, we further show that prokaryotes use different glycolytic pathways depending on their energy supply. Specifically, energy-deprived anaerobes overwhelmingly rely upon the higher ATP yield of the EMP pathway, whereas the ED pathway is common among facultative anaerobes and even more common among aerobes. In addition to demonstrating how protein costs can explain the use of alternative metabolic strategies, this study illustrates a direct connection between an organism's environment and the thermodynamic and biochemical properties of the metabolic pathways it employs.
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Other studies have reported overall free energy changes through glycolysis from −30 to −70 kJ/mol.
“Other studies have reported overall free energy changes from −30 to −70 kJ/mol (Flamholz et al., 2013; Park et al., 2016)”
From Fundamental behaviors emerge from simulations of a living minimal cell (2022) · cites this paper as Flamholz et al., 2013
The Results section says the ED and EMP glycolytic pathways’ net reactions are quite exergonic, supporting a negative overall free-energy change. It does not report an overall range of −30 to −70 kJ/mol. The kJ/mol values in the Fig. 3 caption describe individual bottleneck reactions, not the overall pathways. (LLM, conf=0.85)
Experimental — accuracy not yet measuredThe main deviation in glycolysis is the FBA reaction, where the kinetic parameters result in a free energy drop of roughly 25 kJ/mol, which has been reported to be less than 10 kJ/mol.
“The main deviation here is again with the FBA reaction where the kinetic parameters result in a free energy drop of roughly 25 kJ/mol which has been reported to be less than 10 kJ/mol (Flamholz et al., 2013; Park et al., 2016).”
From Fundamental behaviors emerge from simulations of a living minimal cell (2022) · cites this paper as Flamholz et al., 2013
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- Authors
- Flamholz, A., Noor, E., Bar-Even, A., Liebermeister, W., & Milo, R.
- Affiliations
- Weizmann Institute of Science (IL)
- Department of Plant Sciences, The Weizmann Institute of Science, Rehovot 76100, Israel; and
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2013-04-29
- Volume
- 110
- Issue
- 24
- Pages
- 10039-10044
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3683749
- OpenAlex
- W2035612098
- Cited by
- 531
- References
- 53
- Citations by year
- 2026: 38 · 2025: 31 · 2024: 40 · 2023: 43 · 2022: 44 · 2021: 43 · 2020: 50 · 2019: 50 · 2018: 31 · 2017: 40 · 2016: 42 · 2015: 36 · 2014: 33 · 2013: 10
- FWCI
- 18.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, other-oa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Leona M. and Harry B. Helmsley Charitable Trust
- Deutsche Forschungsgemeinschaft (Ll1676/2-1)
- Azrieli Foundation
- FP7 Ideas: European Research Council (260392)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial metabolism and enzyme function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- glycolysis, Entner-Doudoroff pathway, ATP yield, enzyme stoichiometry, thermodynamics of metabolism, energy deprivation, anaerobic bacteria, facultative anaerobes, aerobic bacteria
- MeSH terms
- Adenosine Triphosphate, Aerobiosis, Algorithms, Anaerobiosis, Bacteria, Bacterial Proteins, Energy Metabolism, Escherichia coli, Glucose, Glycolysis, Kinetics, Models, Biological, Phylogeny, Prokaryotic Cells, Species Specificity, Thermodynamics, Metabolic Networks and Pathways
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