Issue 8, 2016

A fuzzy logic controller based approach to model the switching mechanism of the mammalian central carbon metabolic pathway in normal and cancer cells

Abstract

Dynamics of large nonlinear complex systems, like metabolic networks, depend on several parameters. A metabolic pathway may switch to another pathway in accordance with the current state of parameters in both normal and cancer cells. Here, most of the parameter values are unknown to us. A fuzzy logic controller (FLC) has been developed here for the purpose of modeling metabolic networks by approximating the reasons for the behaviour of a system and applying expert knowledge to track switching between metabolic pathways. The simulation results can track the switching between glycolysis and gluconeogenesis, as well as glycolysis and pentose phosphate pathways (PPP) in normal cells. Unlike normal cells, pyruvate kinase (M2 isoform) (PKM2) switches alternatively between its two oligomeric forms, i.e. an active tetramer and a relatively low activity dimer, in cancer cells. Besides, there is a coordination among PKM2 switching and enzymes catalyzing PPP. These phenomena help cancer cells to maintain their high energy demand and macromolecular synthesis. However, the reduction of initial adenosine triphosphate (ATP) to a very low concentration, decreasing initial glucose uptake, destroying coordination between glycolysis and PPP, and replacement of PKM2 by its relatively inactive oligomeric form (dimer) or inhibition of the translation of PKM2 may destabilize the mutated control mechanism of the mammalian central carbon metabolic (CCM) pathway in cancer cells. The performance of the model is compared appropriately with some existing ones.

Graphical abstract: A fuzzy logic controller based approach to model the switching mechanism of the mammalian central carbon metabolic pathway in normal and cancer cells

Supplementary files

Article information

Article type
Paper
Submitted
18 Feb 2016
Accepted
10 May 2016
First published
26 May 2016

Mol. BioSyst., 2016,12, 2490-2505

A fuzzy logic controller based approach to model the switching mechanism of the mammalian central carbon metabolic pathway in normal and cancer cells

A. Dasgupta, D. Paul and R. K. De, Mol. BioSyst., 2016, 12, 2490 DOI: 10.1039/C6MB00131A

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