Regulation in metabolic systems under homeostatic flux control

The general properties of metabolic systems under homeostatic flux control are analyzed. It is shown that the main characteristic point for an enzyme in such a system is a sharp transition from limitation outside the system to limitation by some enzyme inside the system. A method for the quantitative treatment of the experimental dependence of metabolic flux on enzyme content is presented. The conception of "nonlimiting," "near-limiting," and "limiting" enzymes is developed for these systems. It is pointed out that reactions close to a thermodynamic equilibrium under normal conditions can considerably limit the homeostatic fluxes. The rules for regulation of fluxes in such systems are illustrated by the data obtained for transgenic plants with reduced activities of some Calvin-cycle enzymes and further examples. A comparison is made between the developed quantitative description of metabolic fluxes under homeostatic flux control and the methods of metabolic control analysis.