Propagation of extrinsic perturbation in a multi-step biochemical pathway
by
Somdatta Sinha
Centre for Cellular & Molecular Biology, Uppal Road, Hyderabad 500007, AP, India
Coauthors: R. Maithreye

Biochemical pathways underlie cellular processes. These pathways are inter-connected chemical reactions forming an intricate network of functional and physical interactions between molecular species in the cell. Many of the steps in a pathway take place at different cellular compartments and hence are subjected to different environmental milieus. It is thus both interesting and surprising as to how such an interacting dynamical system can faithfully transmit signals in spite of perturbations of different types acting at different steps of the multi-step process. Using a simple three-step negatively auto-regulated model pathway, we show that the effect of perturbation at different steps of the pathway and its transmission through the network is dependent on the context (i.e., the position) of the particular reaction step in relation to the topology of the regulatory network, stoichiometry of reactions, type of nonlinearity involved in the reactions and also on the intrinsic dynamical state of the pathway variables. We delineate the qualitative and quantitative changes in the pathway dynamics for constant (‘bias’) and random external perturbations acting on the pathway steps locally or globally to all steps. We show that constant perturbation induces qualitative change in dynamics, whereas random fluctuations cause significant quantitative variations in the concentrations of the different variables. Thus, the dynamic response of multi-step biochemical pathways to external perturbation depends on their biochemical, topological and dynamical features.

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Date received: February 9, 2008