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A Delayed Mass-Action Model for the Transcriptional Control of Hmp, an NO Detoxifying Enzyme, by the Iron-Sulfur Protein FNR

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Delays and Interconnections: Methodology, Algorithms and Applications

Part of the book series: Advances in Delays and Dynamics ((ADVSDD,volume 10))

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Abstract

In Escherichia coli, an enzyme called Hmp is a key contributor to the detoxification of nitric oxide (NO). In the absence of NO, the transcription of the hmp gene is repressed by an iron-sulfur protein called FNR. NO damages the iron-sulfur cluster of FNR, weakening the repression of hmp and allowing expression of Hmp to high levels. A delayed mass-action model for the Hmp-FNR network has been developed. This model has 33 parameters, all but three of which were estimated. One of the unknown parameters, the rate of NO inflow into the cell’s cytoplasm, was used as a control parameter in a study of the steady-state structure of this model. This study revealed bistability across a wide range of inflow rates, oxygen concentrations, and values of the unknown parameters. The bistability is caused by substrate inhibition of Hmp by NO, which allows for a high-NO steady state, which would likely be lethal, to coexist with a biologically desirable low-NO steady state.

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Acknowledgements

I would like to thank Professor Nick Le Brun of the University of East Anglia for answering some of my questions about this system. This work was supported by the Natural Sciences and Engineering Research Council of Canada.

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Authors and Affiliations

  1. Alberta RNA Research and Training Institute, Department of Chemistry and Biochemistry, University of Lethbridge, Lethbridge, Alberta, T1K 3M4, Canada

    Marc R. Roussel

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  1. Marc R. Roussel
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Correspondence to Marc R. Roussel .

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Editors and Affiliations

  1. Laboratoire des Signaux et Systèmes, CNRS-CentraleSupèlec-Université Paris-Saclay, Gif-sur-Yvette, France

    Giorgio Valmorbida

  2. Laboratoire d’Analyse et d’Architecture de Systèmes-CNRS, Toulouse, France

    Alexandre Seuret

  3. Laboratoire des Signaux et Systèmes, CNRS-CentraleSupèlec-Université Paris-Saclay, Gif-sur-Yvette, France

    Islam Boussaada

  4. Mechanical and Industrial Engineering, Northeastern University, Boston, MA, USA

    Rifat Sipahi

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Roussel, M.R. (2019). A Delayed Mass-Action Model for the Transcriptional Control of Hmp, an NO Detoxifying Enzyme, by the Iron-Sulfur Protein FNR. In: Valmorbida, G., Seuret, A., Boussaada, I., Sipahi, R. (eds) Delays and Interconnections: Methodology, Algorithms and Applications. Advances in Delays and Dynamics, vol 10. Springer, Cham. https://doi.org/10.1007/978-3-030-11554-8_14

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