Metabolic flux analysis of an underdetermined network of CHO cells [abstract]

The flux distribution in a detailed metabolic network of CHO-320 cells is evaluated using Metabolic Flux Analysis. As in many practical situations, the available information are not sufficient to completely define the metabolic fluxes, and so, the mass balance system of equations is underdetermined. However, the measurements of the time evolution of a number of extracellular components can provide a set of constraints on the metabolic network, so that a range of possible (non-negative) solutions for each metabolic reaction can be computed instead. In this way, metabolic flux intervals can be established for each intra-extracellular flux in the metabolic network. Moreover, the incorporation of simple theoretical assumptions or the addition of further extracellular measurements, result in the determination of certain metabolic fluxes and the delimitation of quite narrow intervals for the others, so providing a good guess of the real flux distribution in CHO-320 cells. An unique flux distribution can also be computed through linear optimization and the definition of some optimality criteria. In addition, the chosen network structure is analyzed in the light of the different possible configurations that the metabolic network can take due to the alternation of some of their reversible reactions.