Metabolic control and its analysis. Extensions to the theory and matrix method

Abstract

The matrix algebra procedure for determining the flux control coefficients of enzymes in metabolic pathways has been extended to allow determination of the concentration control coefficients. Although it is shown that the procedure is essentially unchanged in most cases, the presence of moiety-conserved cycles in a pathway places additional limitations on the form of the equations that can be used in the matrix formulation for concentration control coefficients. In the case of branched pathways, a new coefficient has been defined, the branch distribution control coefficient, which can be obtained via the matrix procedure. Thus a single matrix equation permits calculation or algebraic evaluation of the control coefficients for flux, concentration and distribution of flux at branches, so that the complete response of a pathway to alteration of enzyme content, or to modulation by an effector, can be determined. The relationships have been determined between flux control coefficients in isolated sections of metabolic pathways and the coefficients for the same enzymes when part of a larger metabolic system. It is shown that the control analysis of the isolated system provides useful information towards determining the control properties of the extended system.