Use of implicit methods from general sensitivity theory to develop a systematic approach to metabolic control. I. Unbranched pathways

Abstract

It is shown that metabolic control theory (MCT), is its present form, is a particular case of general sensitivity theory, which studies the effects of parameter variations on the behavior of dynamic systems. It has been shown that metabolic control theory is obtained from this more general theory for the particular case of steady-state and linear relationships between velocities and enzyme concentrations. In such conditions the relationships between elasticities and flux control coefficients are easily obtained. These relationships are in the form of a matrix product constructed in a priori form. Relationships between combined response coefficients and concentration control coefficients are presented. The use of implicit methodology from general sensitivity theory provides a generalization of MCT, which is applied to unbranched pathways. For this particular case, provided the matrices have been properly constructed, the matrix of global properties (flux and concentration control coefficients) can be obtained by inversion of the matrix of local properties (elasticities). The theorems of MCT (concentration summation, flux summation, flux connectivity, and concentration connectivity) applicable for unbranched pathways are directly obtained by inspection of the matrix product. With these results, the present theoretical basis of MCT is extended with a more structured framework that allows a wider range of application. The results make clearer the relatedness of MCT to the more general approach provided by biochemical systems theory (BST).