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Metabolites 2015, 5(4), 766-793; doi:10.3390/metabo5040766

Quasi-Steady-State Analysis based on Structural Modules and Timed Petri Net Predict System’s Dynamics: The Life Cycle of the Insulin Receptor

1
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
2
Sanofi Aventis Deutschland GmbH, 65926 Frankfurt am Main, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Kazuyuki Shimizu
Received: 11 September 2015 / Revised: 23 November 2015 / Accepted: 9 December 2015 / Published: 17 December 2015
(This article belongs to the Special Issue Metabolic Flux Analysis)
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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. View Full-Text
Keywords: insulin receptor; Petri net; timed Petri net; transition invariant; functional modules; quasi-steady state insulin receptor; Petri net; timed Petri net; transition invariant; functional modules; quasi-steady state
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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MDPI and ACS Style

Scheidel, J.; Lindauer, K.; Ackermann, J.; Koch, I. Quasi-Steady-State Analysis based on Structural Modules and Timed Petri Net Predict System’s Dynamics: The Life Cycle of the Insulin Receptor. Metabolites 2015, 5, 766-793.

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