title: How important is thermodynamics for identifying elementary flux modes?
abstract: We present a method for computing thermodynamically feasible elementary flux modes (tEFMs) using equilibrium constants without need of internal metabolite concentrations. The method is compared with the method based on a binary distinction between reversible and irreversible reactions. When all reactions are reversible, adding the constraints based on equilibrium constants reduces the number of elementary flux modes (EFMs) by a factor of two. Declaring in advance some reactions as irreversible, based on reliable biochemical expertise, can in general reduce the number of EFMs by a greater factor. But, even in this case, computing tEFMs can rule out some EFMs which are biochemically irrelevant. We applied our method to two published models described with binary distinction: the monosaccharide metabolism and the central carbon metabolism of Chinese hamster ovary cells. The results show that the binary distinction is in good agreement with biochemical observations. Moreover, the suppression of the EFMs that are not consistent with the equilibrium constants appears to be biologically relevant.
authors.affiliation: LRI, Université Paris-Sud, CNRS, Université Paris-Saclay, 91405 Orsay, France.|MaIAGE, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Sabine
authors.initials: S
authors.lastname: Peres
authors.affiliation: Research Laboratory in Applied Metabolic Engineering, Department of Chemical Engineering, École Polytechnique de Montréal, P.O. Box 6079, Centre-ville Station, Montreal (Quebec), Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Jolicœur
authors.affiliation: LRI, Université Paris-Sud, CNRS, Université Paris-Saclay, 91405 Orsay, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Moulin
authors.affiliation: LRI, Université Paris-Sud, CNRS, Université Paris-Saclay, 91405 Orsay, France.|MaIAGE, INRA, Université Paris-Saclay, 78350 Jouy-en-Josas, France.
authors.forename: Philippe
authors.identifier: http://orcid.org/0000-0003-1679-0804
authors.initials: P
authors.lastname: Dague
authors.affiliation: Department of Bioinformatics, Friedrich Schiller University of Jena, 07743 Jena, Germany.
authors.forename: Stefan
authors.identifier: http://orcid.org/0000-0003-0470-9802
authors.initials: S
authors.lastname: Schuster
mesh_terms: D000818:Animals; D016466:CHO Cells; D002244:Carbon / Q000378:metabolism; D003198:Computer Simulation; D006224:Cricetinae; D003412:Cricetulus; D064688:Metabolic Flux Analysis / Q000379:methods; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D008954:Models, Biological; D009005:Monosaccharides / Q000378:metabolism; D013816:Thermodynamics
chemical_list: D009005:Monosaccharides; D002244:Carbon