title: Lower glycolysis carries a higher flux than any biochemically possible alternative.
abstract: The universality of many pathways of core metabolism suggests a strong role for evolutionary selection, but it remains unclear whether existing pathways have been selected from a large or small set of biochemical possibilities. To address this question, we construct in silico all possible biochemically feasible alternatives to the trunk pathway of glycolysis and gluconeogenesis, one of the most highly conserved pathways in metabolism. We show that, even though a large number of alternative pathways exist, the alternatives carry lower flux than the real pathway under typical physiological conditions. We also find that if physiological conditions were different, different pathways could outperform those found in nature. Together, our results demonstrate how thermodynamic and biophysical constraints restrict the biochemical alternatives that are open to evolution, and suggest that the existing trunk pathway of glycolysis and gluconeogenesis may represent a maximal flux solution.
authors.affiliation: SUPA, School of Physics and Astronomy, University of Edinburgh, James Clerk Maxwell Building, Peter Guthrie Tait Road, Edinburgh EH9 3FD, UK.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Court
authors.affiliation: SUPA, School of Physics and Astronomy, University of Edinburgh, James Clerk Maxwell Building, Peter Guthrie Tait Road, Edinburgh EH9 3FD, UK.
authors.forename: Bartlomiej
authors.identifier: http://orcid.org/0000-0001-5355-7994
authors.initials: B
authors.lastname: Waclaw
authors.affiliation: SUPA, School of Physics and Astronomy, University of Edinburgh, James Clerk Maxwell Building, Peter Guthrie Tait Road, Edinburgh EH9 3FD, UK.
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Allen
mesh_terms: D005075:Biological Evolution; D003198:Computer Simulation; D005943:Gluconeogenesis; D006019:Glycolysis; D008956:Models, Chemical