Metabolic flux interval analysis of CHO cells

Based on a detailed metabolic network of CHO-320 cells built using available information gathered from published reports, the flux distribution can be evaluated using tools of positive linear algebra (in particular, the algorithm METATOOL devised in T. Pfeiffer and Schuster (1999); S. Schuster (1999)), and to study the influence of the interconnection level of the network as well as the availability of specific measurement information on this flux distribution. As this latter information is usually not sufficient to completely define the metabolic fluxes (i.e., the linear system of equations is underdetermined and an infinity of solution exists), it is of interest to compute the range of possible (non-negative) solutions. Interestingly, depending on the available measurements, the intervals obtained for the intracellular fluxes can be quite narrow, especially for the fluxes surrounding the central metabolism. In this study, the construction of the metabolic network and the selection of its structure (depending on the cell life cycle) are discussed with a view to the determination of the flux distribution. In addition, the sensitivity of the solution space to the availability of specific measurements is assessed.