The mathematics of metabolic control analysis revisited

In this minireview, several different approaches to derivation of the theorems and relationships of Metabolic Control Analysis (MCA) are discussed and an alternative approach is presented. This new approach consists of solving the steady-state mass balances for the intracellular metabolites using linearized kinetics. The application of linearized kinetics reflects the fact that MCA is based on linearization of the system equations in a reference steady state. Our derivation is valid for metabolic networks of arbitrary complexity, including those containing conserved moieties and branches. The value of our approach is its simplicity: the derivation is straightforward and therefore easy to follow. It can serve as a compact introduction to the mathematical basis of MCA.