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Analysis of Homeostatic Mechanisms in Biochemical Networks.

Publication ,  Journal Article
Reed, M; Best, J; Golubitsky, M; Stewart, I; Nijhout, HF
Published in: Bulletin of mathematical biology
November 2017

Cell metabolism is an extremely complicated dynamical system that maintains important cellular functions despite large changes in inputs. This "homeostasis" does not mean that the dynamical system is rigid and fixed. Typically, large changes in external variables cause large changes in some internal variables so that, through various regulatory mechanisms, certain other internal variables (concentrations or velocities) remain approximately constant over a finite range of inputs. Outside that range, the mechanisms cease to function and concentrations change rapidly with changes in inputs. In this paper we analyze four different common biochemical homeostatic mechanisms: feedforward excitation, feedback inhibition, kinetic homeostasis, and parallel inhibition. We show that all four mechanisms can occur in a single biological network, using folate and methionine metabolism as an example. Golubitsky and Stewart have proposed a method to find homeostatic nodes in networks. We show that their method works for two of these mechanisms but not the other two. We discuss the many interesting mathematical and biological questions that emerge from this analysis, and we explain why understanding homeostatic control is crucial for precision medicine.

Duke Scholars

Published In

Bulletin of mathematical biology

DOI

EISSN

1522-9602

ISSN

0092-8240

Publication Date

November 2017

Volume

79

Issue

11

Start / End Page

2534 / 2557

Related Subject Headings

  • Systems Biology
  • Models, Biological
  • Methionine
  • Metabolic Networks and Pathways
  • Mathematical Concepts
  • Kinetics
  • Humans
  • Homeostasis
  • Folic Acid
  • Feedback, Physiological
 

Citation

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Reed, M., Best, J., Golubitsky, M., Stewart, I., & Nijhout, H. F. (2017). Analysis of Homeostatic Mechanisms in Biochemical Networks. Bulletin of Mathematical Biology, 79(11), 2534–2557. https://doi.org/10.1007/s11538-017-0340-z
Reed, Michael, Janet Best, Martin Golubitsky, Ian Stewart, and H Frederik Nijhout. “Analysis of Homeostatic Mechanisms in Biochemical Networks.Bulletin of Mathematical Biology 79, no. 11 (November 2017): 2534–57. https://doi.org/10.1007/s11538-017-0340-z.
Reed M, Best J, Golubitsky M, Stewart I, Nijhout HF. Analysis of Homeostatic Mechanisms in Biochemical Networks. Bulletin of mathematical biology. 2017 Nov;79(11):2534–57.
Reed, Michael, et al. “Analysis of Homeostatic Mechanisms in Biochemical Networks.Bulletin of Mathematical Biology, vol. 79, no. 11, Nov. 2017, pp. 2534–57. Epmc, doi:10.1007/s11538-017-0340-z.
Reed M, Best J, Golubitsky M, Stewart I, Nijhout HF. Analysis of Homeostatic Mechanisms in Biochemical Networks. Bulletin of mathematical biology. 2017 Nov;79(11):2534–2557.
Journal cover image

Published In

Bulletin of mathematical biology

DOI

EISSN

1522-9602

ISSN

0092-8240

Publication Date

November 2017

Volume

79

Issue

11

Start / End Page

2534 / 2557

Related Subject Headings

  • Systems Biology
  • Models, Biological
  • Methionine
  • Metabolic Networks and Pathways
  • Mathematical Concepts
  • Kinetics
  • Humans
  • Homeostasis
  • Folic Acid
  • Feedback, Physiological