Metabolic Control Analysis: Sensitivity of Control Coefficients to Experimentally Determined Variables

Metabolic Control Analysis has provided tools for understanding and quantifying the regulation of biochemical systems, but the values of control coefficients in non-trivial systems can depend on the values of a large number of quantities: metabolite concentrations, fluxes and elasticity coefficients. This poses two related questions. One concerns the accuracy and precision of the values obtained for the control coefficients, depending as they do on a large number of experimentally determined values. The second concerns the importance of the variables in determining the values of the control coefficients: as these variables represent components of the biochemical system under consideration, this corresponds to the question of how do the components determine the regulatory properties of the system? This paper describes an extension to an earlier sensitivity analysis of the control coefficients that can be used to answer both of these questions. The analysis has been incorporated into a computer program (MetaCon), so enabling rapid and automatic determination of the sensitivities of each of the control coefficients to each of the experimental quantities. The program has been used to analyse the control coefficients of two experimental systems taken from the literature. The results of the analysis are presented. Two important points arise: control coefficients in a given biochemical system can show wide variations in their sensitivities to experimental error but, for non-trivial systems, experimental errors of greater than 10-20% may well result in unacceptable errors in calculated control coefficients.