Influence of experimental errors on the determination of flux control coefficients from transient metabolite concentrations

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Abstract
The influence of experimental errors on the determination of flux control coefficients from transient metabolite concentrations with the method proposed by Delgado and Liao [(1992) Biochem. J. 282, 919–927] has been investigated by using Monte Carlo simulations. The method requires least-squares fitting of the transient metabolite concentrations. Three different fitting methods have been evaluated. Simulated metabolite concentrations of a fictive metabolic pathway were scattered randomly, emulating experimental errors, before performing the fits. This was repeated a large number of times; the mean values and standard deviations of the resulting control coefficients are reported. The results show that the proposed method for determining control coefficients is too sensitive to experimental errors to be practicable, with theoretically justified fitting methods. This is in particular due to the high degree of correlation between the concentrations. An alternative ad hoc fitting method produced biased mean values of the estimates of the control coefficients, but with remarkably low standard deviations.