A new constraint-based description of the steady-state flux cone of metabolic networks

Metabolic pathway analysis is an important area in computational biology, which has received considerable attention in the recent past. The set of all possible flux distributions over a metabolic network at steady state defines a polyhedral cone, the steady-state flux cone. Two major approaches exist to characterize this cone: elementary flux modes and extreme pathways. Both use an inner description of the flux cone, which is based on sets of generating vectors. The number of these generators may be very large even for small networks. This limits the practical applicability of these methods. We present a new constraint-based approach to metabolic pathway analysis which uses an outer description of the flux cone, based on sets of non-negativity constraints. These can be identified with irreversible reactions and thus have a direct biochemical interpretation. The resulting description of the flux cone is minimal and unique. Furthermore, it satisfies a simplicity condition similar to the one that holds for elementary flux modes. (c) 2008 Elsevier B.V. All rights reserved.