IDENTIFYING RATE-CONTROLLING ENZYMES IN METABOLIC PATHWAYS WITHOUT KINETIC-PARAMETERS

The flux control coefficients, originally defined by Kacser and Burns, provide a sound theoretical basis for identifying rate-controlling enzymes in metabolic pathways. However, the calculation of these quantities requires kinetic parameters, which are usually unavailable in practical systems. This article presents a method for evaluating the flux control coefficients by using measurements of metabolite concentrations in a transient state. The basis of this approach is the relationship identified here between transient fluxes and the flux control coefficients. Principal component analysis in the form of singular value decomposition is used to identify such relationships and evaluate the flux control coefficients. The approach does not require kinetic parameters and depends only on the knowledge of pathway stoichiometry, which is generally available.