Steady-state modelling of metabolic flux between the tricarboxylic acid cycle and the glyoxylate bypass in Escherichia coli.

Abstract

In this study, mathematical modelling, using the computer package MetaModel, was employed to calculate the steady-state fluxes and the concentration of various metabolites of the central pathways during growth of Escherichia coli on acetate. This package also enabled us to formulate the matrices of the elasticity coefficients and the control and response coefficients under different steady states. In this paper, we have assessed the relative contribution of the competing enzymes at the metabolic junction of isocitrate, i.e. isocitrate dehydrogenase (ICDH) and isocitrate lyase (ICL), to the overall distribution of carbon flux among the enzymes of the central pathways thus extending the pioneering work of Walsh and Koshland on the partition of carbon flux between the two metabolic cycles of the tricarboxylic acid and the glyoxylate bypass. This study revealed that ICDH is not 'rate limiting' during growth on acetate and that flux through ICL is essential not only to replenish the central pathways with biosynthetic precursors but also to sustain a high intracellular level of isocitrate. Furthermore, above certain threshold concentration of ICL, the Krebs cycle and the glyoxylate bypass work in concert and the partition of carbon flux between ICDH and ICL is no longer a problem.