Metabolic control analysis for large changes: extension to variable elasticity coefficients.

Modular approaches are powerful systems biology strategies to deal with complexity. They consist in lumping conceptually all that is irrelevant to the problem under study, leaving explicit the portions of interest. Modular (or top-down) metabolic control analysis is a theoretical and experimental approach to study the sensitivity properties of complex metabolic systems. Initially, it was conceived for infinitesimal changes but, recently, it started to be developed for large metabolic changes. A central result of this approach is that the systemic properties, represented by control coefficients, can be expressed as a function of the properties of isolated modules, the elasticity coefficients. Here we extend the theory for large changes to the case that the elasticity coefficients depend on the extent of the change. The novel theory is used to analyse experimental data related to the control of glycolytic flux in Escherichia coli. Our analysis shows that the pattern of control for large changes is quantitatively and qualitatively different from the one obtained applying the infinitesimal treatment.