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

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 asingle-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.

[1]  B. Buchanan,et al.  A new ferredoxin-dependent carbon reduction cycle in a photosynthetic bacterium. , 1966, Proceedings of the National Academy of Sciences of the United States of America.

[2]  R. Annett,et al.  Oxalacetate keto-enol tautomerase. Purification and characterization. , 1969, The Journal of biological chemistry.

[3]  P. W. Hochachka,et al.  Invertebrate Facultative Anaerobiosis , 1972, Science.

[4]  R. Lemmon Chemical Evolution , 1972, Nature.

[5]  J. Lawless,et al.  Dicarboxylic acids from electric discharge , 1974, Nature.

[6]  A. Duffield,et al.  Dicarboxylic acids in the Murchison meteorite , 1974, Nature.

[7]  F. Jacob,et al.  Evolution and tinkering. , 1977, Science.

[8]  Jack E. Baldwin,et al.  The evolution of metabolic cycles , 1981, Nature.

[9]  J. Beatty,et al.  Biosynthetic and Bioenergetic Functions of Citric Acid Cycle Reactions in Rhodopseudomonas capsulata , 1981, Journal of bacteriology.

[10]  H. Gest Evolution of the citric acid cycle and respiratory energy conversion in prokaryotes , 1981 .

[11]  E. Meléndez-Hevia,et al.  The game of the pentose phosphate cycle. , 1985, Journal of theoretical biology.

[12]  R. Dawkins The Blind Watchmaker , 1986 .

[13]  T. G. Waddell,et al.  Chemical evolution of the citric acid cycle: sunlight photolysis of alpha-ketoglutaric acid. , 1987, Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life.

[14]  P. Weitzman,et al.  Krebs' citric acid cycle : half a century and still turning , 1987 .

[15]  H. Gest Evolutionary roots of the citric acid cycle in prokaryotes. , 1987, Biochemical Society symposium.

[16]  R. Thauer Citric-acid cycle, 50 years on , 1988 .

[17]  E. Meléndez-Hevia,et al.  Economy of design in metabolic pathways: further remarks on the game of the pentose phosphate cycle. , 1988, Journal of theoretical biology.

[18]  E. Meléndez-Hevia,et al.  The game of the pentose phosphate cycle: a mathematical approach to study the optimization in design of metabolic pathways during evolution. , 1990, Biomedica biochimica acta.

[19]  R. Mortlock The Evolution of Metabolic Function , 1992 .

[20]  H. Gottlieb,et al.  Enol oxalacetic acid exists in the Z form in the crystalline state and in solution , 1992 .

[21]  E. Meléndez-Hevia,et al.  Optimization of molecular design in the evolution of metabolism: the glycogen molecule. , 1993, The Biochemical journal.

[22]  Richard Dawkins,et al.  The eye in a twinkling , 1994, Nature.

[23]  F. Montero,et al.  Optimization of Metabolism: The Evolution of Metabolic Pathways Toward Simplicity Through the Game of the Pentose Phosphate Cycle , 1994 .

[24]  A. Spormann,et al.  Anaerobic acetate oxidation to CO2 by Desulfotomaculum acetoxidans , 1988, Archives of Microbiology.

[25]  B. Buchanan,et al.  A reverse KREBS cycle in photosynthesis: consensus at last , 2004, Photosynthesis Research.

[26]  A. Spormann,et al.  Anaerobic acetate oxidation to CO2 by Desulfotomaculum acetoxidans , 1989, Archives of Microbiology.

[27]  F. Widdel,et al.  Acetate oxidation to CO2 in anaerobic bacteria via a novel pathway not involving reactions of the citric acid cycle , 1986, Archives of Microbiology.

[28]  T. G. Waddell,et al.  Chemical evolution of the citric acid cycle: Sunlight and ultraviolet photolysis of cycle intermediates , 2005, Origins of life and evolution of the biosphere.

[29]  Chemical evolution of the citric acid cycle: Sunlight photolysis of the amino acids glutamate and aspartate , 1992, Origins of life and evolution of the biosphere.