Control-pattern analysis of metabolic pathways. Flux and concentration control in linear pathways.

Metabolic control analysis [Kacser and Burns (1973) Symp. Soc. Exp. Biol. 27, 65-104; Heinrich and Rapoport (1974) Eur. J. Biochem. 42, 89-95] leads to a description of the systemic properties of a metabolic system (expressed as control coefficients) in terms of the local kinetic properties of the individual enzyme-catalyzed reactions (expressed as elasticity coefficients). This paper describes a non-algebraic diagrammatic method which generates the mathematical expressions for flux or concentration-control coefficients in terms of elasticity coefficients. According to a set of simple rules, 'flux-control patterns' or 'concentration-control patterns' are drawn on a metabolic diagram. Each control pattern represents a product of elasticity coefficients that occurs as a term in the expression for a control coefficient. The rules also generate the correct sign that precedes each term. The control patterns are then used to build the expressions for control coefficients. The procedure was developed in such a way that each control pattern can be understood in terms of a 'chain of local effects' which shows how a perturbation in the activity of an enzyme is propagated through the metabolic pathway.