Effects of topology and feedback inhibition on multistability and robustness of metabolic pathways

CAROLINA COGO; DIEGO FG VALLEJO; AUGUSTO MELGAREJO; ANÍBAL R. LODEIRO

Sierra de la Ventana

Congreso; XLIII Reunión Anual de la Sociedad Argentina de Biofísica; 2014

Sociedad Argentina de Biofísica

Metabolic systems are open systems in steady state out of equilibrium, which means that the concentrations of metabolites do not change over time. These systems consist of a large number of metabolites linked by enzyme-catalyzed reactions, which occur in linear or cyclic sequences. To analyze how the topology and regulation of metabolic networks influence its robustness, we proposed four simple ways in which three metabolites are linked by reactions catalyzed by enzymes that obey the Michaelis-Menten kinetics. The regulation of each pathway was modeled as a feedback inhibition of the latter metabolite on the first reaction. Furthermore, we assumed that the state of the system is determined by a vector whose components are the concentrations of all the metabolites involved. To perturb the system, we randomly modified the enzyme concentrations of the pathway in a range of 50-fold, generating a multistable steady-state system where each cell in the population contained a given concentration of each enzyme, and thus a particular set of metabolite concentrations. This set of metabolite concentrations defined the state of the system. By evaluating how these states were dispersed in response to enzyme variation, we evaluated the robustness of the system. Our results indicate that cyclic topologies promote multistable dispersion of system states, while linear topologies promote robustness. Regulation by feedback inhibition increases multistability when the topologies contain linear stretches.