The puzzle of the Krebs citric acid cycle: Assembling the pieces of chemically feasible reactions, and opportunism in the design of metabolic pathways during evolution (original) (raw)
Abstract
The evolutionary origin of the Krebs citric acid cycle has been for a long time a model case in the understanding of the origin and evolution of metabolic pathways: How can the emergence of such a complex pathway be explained? A number of speculative studies have been carried out that have reached the conclusion that the Krebs cycle evolved from pathways for amino acid biosynthesis, but many important questions remain open: Why and how did the full pathway emerge from there? Are other alternative routes for the same purpose possible? Are they better or worse? Have they had any opportunity to be developed in cellular metabolism evolution? We have analyzed the Krebs cycle as a problem of chemical design to oxidize acetate yielding reduction equivalents to the respiratory chain to make ATP. Our analysis demonstrates that although there are several different chemical solutions to this problem, the design of this metabolic pathway as it occurs in living cells is the best chemical solution: It has the least possible number of steps and it also has the greatest ATP yielding. Study of the evolutionary possibilities of each one-taking the available material to build new pathways-demonstrates that the emergence of the Krebs cycle has been a typical case of opportunism in molecular evolution. Our analysis proves, therefore, that the role of opportunism in evolution has converted a problem of several possible chemical solutions into a_single-solution problem_, with the actual Krebs cycle demonstrated to be the best possible chemical design. Our results also allow us to derive the rules under which metabolic pathways emerged during the origin of life.
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Abbreviations
pyr:
pyruvate
OAA:
oxaloacetate
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Authors and Affiliations
- Departamento de Bioquímica, Facultad de Biología, Universidad de La Laguna, 38206 Tenerife, Canary Islands, Spain
Enrique Meléndez-Hevia - Department of Chemistry, University of Tennessee at Chattanooga, 615 McCallie Avenue, 37403, Chattanooga, TN, USA
Thomas G. Waddell - Departamento de Bioquímica, Facultad de Química, Universidad de Barcelona, Martí i Franqués 1, 08028, Barcelona, Spain
Marta Cascante
Authors
- Enrique Meléndez-Hevia
- Thomas G. Waddell
- Marta Cascante
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Correspondence to: E. Meléndez-Hevia
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Meléndez-Hevia, E., Waddell, T.G. & Cascante, M. The puzzle of the Krebs citric acid cycle: Assembling the pieces of chemically feasible reactions, and opportunism in the design of metabolic pathways during evolution.J Mol Evol 43, 293–303 (1996). https://doi.org/10.1007/BF02338838
- Received: 10 May 1995
- Accepted: 03 November 1996
- Issue date: September 1996
- DOI: https://doi.org/10.1007/BF02338838