Analysis of Homeostatic Mechanisms in Biochemical Networks.

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Reed, M; Best, J; Golubitsky, M; Stewart, I; Nijhout, HF

Published Date

  • November 2017

Published In

Volume / Issue

  • 79 / 11

Start / End Page

  • 2534 - 2557

PubMed ID

  • 28884446

Electronic International Standard Serial Number (EISSN)

  • 1522-9602

International Standard Serial Number (ISSN)

  • 0092-8240

Digital Object Identifier (DOI)

  • 10.1007/s11538-017-0340-z

Language

  • eng