Control-Pattern Analysis of Metabolic Systems

Abstract

How do fluxes and metabolite concentrations, the variables of metabolic systems, respond to a change in some system parameter, such as an enzyme concentration or the affinity of an enzyme towards one of its effectors? Can such systemic behaviour be explained purely in terms of local enzymic properties? These fundamental questions about metabolic behaviour have been successfully addressed by metabolic control analysis (Kacser & Burns, 1973; Heinrich & Rapoport, 1974; also in numerous chapters of this book) and biochemical systems theory (Savageau, 1969abc, 1976; also in Chapters 4 and 5 of this book by Savageau and Voit respectively). In the language of metabolic control analysis the answer amounts to expressing control coefficients, which quantify global systemic behaviour, in terms of elasticity coefficients, which describe local enzymic behaviour. Similar coefficients are defined in biochemical systems theory. It is immaterial whether one derives these expressions from the summation and connectivity relationships of metabolic control analysis or the power law equations of biochemical systems theory. In metabolic control analysis, several methods of solution involving matrix algebra have been developed (Fell & Sauro, 1985; Sauro et al., 1987; Small & Fell, 1989; Westerhoff & Kell, 1986) and they allow for the analysis of flux and concentration control in metabolic pathways containing linear, branched, looped and moiety-conserved structures. These methods are eminently suitable for numerical control analysis, but can be tedious for obtaining the algebraic solution.