title: Quasi-Steady-State Analysis based on Structural Modules and Timed Petri Net Predict System's Dynamics: The Life Cycle of the Insulin Receptor.
abstract: The insulin-dependent activation and recycling of the insulin receptor play an essential role in the regulation of the energy metabolism, leading to a special interest for pharmaceutical applications. Thus, the recycling of the insulin receptor has been intensively investigated, experimentally as well as theoretically. We developed a time-resolved, discrete model to describe stochastic dynamics and study the approximation of non-linear dynamics in the context of timed Petri nets. Additionally, using a graph-theoretical approach, we analyzed the structure of the regulatory system and demonstrated the close interrelation of structural network properties with the kinetic behavior. The transition invariants decomposed the model into overlapping subnetworks of various sizes, which represent basic functional modules. Moreover, we computed the quasi-steady states of these subnetworks and demonstrated that they are fundamental to understand the dynamic behavior of the system. The Petri net approach confirms the experimental results of insulin-stimulated degradation of the insulin receptor, which represents a common feature of insulin-resistant, hyperinsulinaemic states.
authors.affiliation: Molecular Bioinformatics, Cluster of Excellence "Macromolecular Complexes", Institute of Computer Science, Johann Wolfgang Goethe-University Frankfurt am Main, Robert-Mayer-Str. 11-15, 60325 Frankfurt am Main, Germany. J.Scheidel@bioinformatik.uni-frankfurt.de.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Scheidel
authors.affiliation: Sanofi Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany. Klaus.Lindauer@sanofi-aventis.com.
authors.forename: Klaus
authors.initials: K
authors.lastname: Lindauer
authors.affiliation: Molecular Bioinformatics, Cluster of Excellence "Macromolecular Complexes", Institute of Computer Science, Johann Wolfgang Goethe-University Frankfurt am Main, Robert-Mayer-Str. 11-15, 60325 Frankfurt am Main, Germany. J.Ackermann@bioinformatik.uni-frankfurt.de.
authors.forename: Jörg
authors.initials: J
authors.lastname: Ackermann
authors.affiliation: Molecular Bioinformatics, Cluster of Excellence "Macromolecular Complexes", Institute of Computer Science, Johann Wolfgang Goethe-University Frankfurt am Main, Robert-Mayer-Str. 11-15, 60325 Frankfurt am Main, Germany. Ina.Koch@bioinformatik.uni-frankfurt.de.
authors.forename: Ina
authors.initials: I
authors.lastname: Koch
keywords: Petri net; functional modules; insulin receptor; quasi-steady state; timed Petri net; transition invariant