Metabolic Flux Analysis of CHO-320 Cells: Underdetermined Network and Effect of Measurement Errors

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 is 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. A unique flux distribution can also be computed through linear optimization and the definition of some optimality criteria. In this article, several of the above-mentioned situations are discussed, highlighting the importance of specific measurements and comparing the flux intervals under some particular assumptions such as optimal biomass growth or no Threonine catabolism. In addition, the influence of the measurement errors on the numerical results is explored using Monte Carlo techniques.