Modelling Simple Biochemical Networks

Abstract

At the cellular level, networks of coupled biochemical reactions underlie all functions - from cell cycle to development. These reactions control and co-ordinate the cellular functions through regulated activities of the genetic and metabolic reactions in a highly repeatable manner, in the face of uncertain external and noisy internal environment [1]. The co-ordinated behaviour exhibited by the cell in response to a variety of signals and perturbations is achieved through various regulatory interactions involving both short and long range feedback loops of the positive and negative type. The cell is quite flexible in its use of types of regulation and uses various combinations of feedback processes for such activities. Nested feedback loops are frequently seen in amino acid biosynthetic pathways, where a single common precursor can lead to the synthesis of more than one amino acid [2]. Living systems seem to have taken advantage of the variability in functional dynamics emerging from a few common components by simply connecting them in different ways. Given the predominance of negative feedback processes and reaction pathways with low connectivity observed in both metabolic and transcriptional regulatory pathways in, E. coli., [3,4], we have studied the canonical three-step single negative feedback system with end product inhibition and compared it to a structurally more complex system in terms of an additional negative feedback. The results of this study of the different topologies of feedback processes, in isolation as well as when they are interacting with each other, show the type of dynamics attainable by these designs under various genetic and biochemical alterations of the pathway. We also evaluate the response of the pathway to perturbation in the end product concentration in order to judge the robustness of the dynamics in that particular topology. Our approach could be a possible way of studying regulation in cellular processes and arriving at a set of minimal designs adopted by nature.