MODULAR ANALYSIS OF THE CONTROL OF COMPLEX METABOLIC PATHWAYS

The understanding of the functioning of the intact cell would be simpl ified appreciably if it were possible first to analyze particular modu les of cell physiology separately, and then to integrate the informati on so as to yield understanding of the control structure in terms of t he mutual regulation of the modules. Here we develop a quantitative me thod based on Metabolic Control Analysis that makes this possible: The relevant properties of the modules are contained in ''overall'' elast icity coefficients, which reflect the changes in fluxes in the module upon a small variation of the environment of the module, allowing the latter to attain steady state. We show how overall control coefficient s, which reflect the control exerted by the processes catalyzed by eac h module, can be expressed into the overall elasticity coefficients. W e derive corresponding summation and connectivity theorems. A number o f possible divisions of physiological systems into modules is discusse d. This work is a generalization of previous analyses of overall contr ol properties in that it allows for multiple fluxes to connect the mod ules, and reaction stoichiometries of any complexity.