MODULAR ANALYSIS OF THE CONTROL OF COMPLEX METABOLIC PATHWAYS

The understanding of the functioning of the intact cell would be simplified appreciably if it were possible first to analyze particular modules of cell physiology separately, and then to integrate the information so as to yield understanding of the control structure in terms of the mutual regulation of the modules. Here we develop a quantitative method based on Metabolic Control Analysis that makes this possible: The relevant properties of the modules are contained in ''overall'' elasticity 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 coefficients, which reflect the control exerted by the processes catalyzed by each module, can be expressed into the overall elasticity coefficients. We derive corresponding summation and connectivity theorems. A number of possible divisions of physiological systems into modules is discussed. This work is a generalization of previous analyses of overall control properties in that it allows for multiple fluxes to connect the modules, and reaction stoichiometries of any complexity.