Metabolic Control Analysis in Theory and Practice

Abstract

Metabolic control analysis is the most widely used modern theoretical framework for analyzing the kinetic behavior of metabolic pathways and other multienzyme systems. It considers the responses of individual enzymes to changes in concentrations of their substrates and other metabolites in terms of elasticities, which correspond approximately to the traditional idea of order of reaction. These are local properties, because they treat each enzyme in isolation from its pathway; there are also systemic properties, which relate the behavior of a system variable such as metabolic flux or the concentration of an intermediate to changes in the external parameters, such as enzyme activities or concentrations of pool or sink metabolites. The most important of these systemic properties are the control coefficients, which express the contributions of the individual enzymes to the total effects on fluxes or metabolite concentrations. They obey summation relationships, implying for example, that control of flux is shared among the enzymes composing the system. Metabolic control analysis allows the classical ideas of metabolic regulation to be placed on a more secure theoretical base, because it allows one to dispense with any assumption that metabolic systems have to be studied in relation to certain regulatory enzymes whose properties define the behavior of the whole system. Instead of assuming the existence of “key enzymes,” metabolic control analysis allows the contribution of each enzyme to be quantified.