INFLUENCE OF EXPERIMENTAL ERRORS ON THE DETERMINATION OF FLUX CONTROLCOEFFICIENTS FROM TRANSIENT METABOLIC CONCENTRATIONS

The influence of experimental errors on the determination of flux cont rol coefficients from transient metabolite concentrations with the met hod proposed by Delgado and Liao [(1992) Biochem. J. 282, 919-927] has been investigated by using Monte Carlo simulations. The method requir es least-squares fitting of the transient metabolite concentrations. T hree different fitting methods have been evaluated. Simulated metaboli te concentrations of a fictive metabolic pathway were scattered random ly, emulating experimental errors, before performing the fits. This wa s repeated a large number of times; the mean values and standard devia tions 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 theoretic ally justified fitting methods. This is in particular due to the high degree of correlation between the concentrations. An alternative ad ho c fitting method produced biased mean values of the estimates of the c ontrol coefficients, but with remarkably low standard deviations.