Errors Associated with Experimental Determinations of Enzyme Flux Control Coefficients

An analysis is presented of the likely statistical error and mathematical bias of experimental enzyme flux control coefficient estimates, calculated from observations of the flux changes caused by finite changes of the concentration of an enzyme in a metabolic pathway. The results indicate that such control coefficients are not likely to be determined with satisfactory precision unless the experimental data are evaluated by hyperbolic regression analysis, and the actual flux vs. enzyme concentration profile conforms closely to a hyperbolic relationship. It is concluded that it may not normally be feasible to obtain reliable experimental estimates of enzyme flux control coefficients in realistic systems by the examined direct approach. Arguments are presented to show that the error situation is unlikely to be more favourable as it concerns that indirect calculation of flux control coefficients from transient-state kinetic data or from experimental estimates of infinitesimally defined quantities such as elasticity coefficients and co-response coefficients.