title: Which sets of elementary flux modes form thermodynamically feasible flux distributions?
abstract: Elementary flux modes (EFMs) are non-decomposable steady-state fluxes through metabolic networks. Every possible flux through a network can be described as a superposition of EFMs. The definition of EFMs is based on the stoichiometry of the network, and it has been shown previously that not all EFMs are thermodynamically feasible. These infeasible EFMs cannot contribute to a biologically meaningful flux distribution. In this work, we show that a set of thermodynamically feasible EFMs need not be thermodynamically consistent. We use first principles of thermodynamics to define the feasibility of a flux distribution and present a method to compute the largest thermodynamically consistent sets (LTCSs) of EFMs. An LTCS contains the maximum number of EFMs that can be combined to form a thermodynamically feasible flux distribution. As a case study we analyze all LTCSs found in Escherichia coli when grown on glucose and show that only one LTCS shows the required phenotypical properties. Using our method, we find that in our E. coli model < 10% of all EFMs are thermodynamically relevant.
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.|Austrian Centre of Industrial Biotechnology, Vienna, Austria.
authors.forename: Matthias P
authors.initials: MP
authors.lastname: Gerstl
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.|Austrian Centre of Industrial Biotechnology, Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Jungreuthmayer
authors.affiliation: Johann Radon Institute for Computational and Applied Mathematics, Austrian Academy of Sciences, Linz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Müller
authors.affiliation: Department of Biotechnology, University of Natural Resources and Life Sciences, Vienna, Austria.|Austrian Centre of Industrial Biotechnology, Vienna, Austria.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Zanghellini
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000465:Algorithms; D003198:Computer Simulation; D004926:Escherichia coli / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D007700:Kinetics; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D008954:Models, Biological; D015233:Models, Statistical; D013816:Thermodynamics
chemical_list: D000255:Adenosine Triphosphate; D005947:Glucose
keywords: constraint-based analysis; metabolic pathway analysis; metabolomics; steady-state flux cone; thermodynamics