Quantifying the Importance of Regulatory Loops in homeostatic Control Mechanisms: Hierarchical Control of DNA Supercoiling

Abstract

Many regulatory structures in the cell appear to aim at maintaining an optimal cellular state. These are here referred to as homeostatic control mechanisms. After a change in environmental conditions a cell adjusts to return as closely as possible to its previous state. Interestingly, these control mechanisms also function after perturbations of the cellular state itself. Apparently this type of regulatory mechanism is not so much addressed from the extracellular as it is from the intracellular environment, a topic dealt with in this volume in Chapter 26. Although the homeostatic control mechanisms are by definition beneficial to the biological system, they can be a nuisance when trying to engineer it. Attempts to manipulate the system tend to be largely overruled by subsequent adaptation. Part of such homeostatic control mechanisms is embedded in the nature of the kinetics of the catalytic steps in the system. On activation of such a step the product of the reaction will increase initially but this increase will lead to both an inhibition of the stimulated step and an activation of the subsequent step in the pathway. In this way, both enzymes surrounding the intermediate will tend to keep the concentration of the latter constant.