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The Problem of Futile Cycles in Metabolic Flux Modeling: Flux Space Characterization and Practical Approaches to Its Solution

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Modelling and Simulation of Diffusive Processes

Part of the book series: Simulation Foundations, Methods and Applications ((SFMA))

Abstract

In the past decade, metabolic flux modeling has been established as an important technique to elucidate detailed snapshot information on a complex cellular system. The basis of such modeling is flux balance analysis, which can identify the optimal flux distribution of a particular phenotype of the system based on physicochemical properties. However, characterization of the functional states of a large-scale system can yield alternate optimal solutions (AOS) and the resultant flux distributions are commonly obscured with the presence of futile cycles in a complex system. Here, we review the current flux modeling techniques for characterization of multiple equally valid cellular phenotypes and explore the fundamentals of the occurrences of futile cycles in a system. We consider that most of the futile cycles are by-products of the numerical techniques and are not biologically relevant. In order to tackle the problem of cycles, we present some rational approaches to efficiently eliminate the meaninglessly high flux values arising from the presence of the cycles, without degrading the functional states of systems. Our novel methods discussed here only use the known stoichiometry of the network and are straightforward to apply.

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Authors and Affiliations

  1. Faculty of Ag & Life Science, Centre for Advanced Computational Solutions (C-fACS), Lincoln University, Lincoln, New Zealand

    Wynand S. Verwoerd & Longfei Mao

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  1. Wynand S. Verwoerd
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  2. Longfei Mao
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Correspondence to Wynand S. Verwoerd .

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Editors and Affiliations

  1. Banaras Hindu University, Varanasi, Uttar Pradesh, India

    S.K. Basu

  2. Banaras Hindu University, Varanasi, Uttar Pradesh, India

    Naveen Kumar

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Verwoerd, W., Mao, L. (2014). The Problem of Futile Cycles in Metabolic Flux Modeling: Flux Space Characterization and Practical Approaches to Its Solution. In: Basu, S., Kumar, N. (eds) Modelling and Simulation of Diffusive Processes. Simulation Foundations, Methods and Applications. Springer, Cham. https://doi.org/10.1007/978-3-319-05657-9_11

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  • DOI: https://doi.org/10.1007/978-3-319-05657-9_11

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