Co-response analysis: a new experimental strategy for metabolic control analysis.

The formulation of the standard summation and connectivity relationships as a statement that the matrix of all the elasticities in a system is the inverse of the matrix of all the control coefficients is completely general, provided that only control coefficients for independent fluxes and concentrations are considered, and that the elasticity matrix is written to take account of the stoichiometry of the pathway and the implied dependences between concentrations. This generally implies that co-response analysis is also general, i.e. that all of the elasticities and all of the control coefficients in any system, regardless of branching, feedback effects, moiety conservation or other complications, can be determined by comparing the effects of perturbations of the enzyme activities on the steady-state fluxes and concentrations of the pathway. The approach requires no quantitative information about the magnitudes of the effects on the individual enzyme activities, and consequently no enzymes need to be studied in isolation from the pathway.