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Approximation of delays in biochemical systems. (English) Zbl 1089.92021
Summary: In the past, metabolic pathway analyses have mostly ignored the effects of time delays that may be due to processes that are slower than biochemical reactions, such as transcription, translation, translocation, and transport. We show within the framework of biochemical systems theory (BST) that delay processes can be approximated accurately by augmenting the original variables and nonlinear differential equations with auxiliary variables that are defined through a system of linear ordinary differential equations. These equations are naturally embedded in the structure of S-systems and generalized mass action systems within BST and can be interpreted as linear signaling pathways or cascades. We demonstrate the approximation method with the simplest generic modules, namely single delayed steps with and without feedback inhibition. These steps are representative though, because they are easily incorporated into larger systems. We show that the dynamics of the approximated systems reflect that of the original delay systems well, as long as the systems do not operate in very close vicinity of threshold values where the systems lose stability. The accuracy of approximation furthermore depends on the selected number of auxiliary variables. In the most relevant situations where the systems operate at states away from their critical thresholds, even a few auxiliary variables lead to satisfactory approximations.

MSC:
92C45 Kinetics in biochemical problems (pharmacokinetics, enzyme kinetics, etc.)
34K28 Numerical approximation of solutions of functional-differential equations (MSC2010)
34K60 Qualitative investigation and simulation of models involving functional-differential equations
34K07 Theoretical approximation of solutions to functional-differential equations
37N25 Dynamical systems in biology
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