How important is thermodynamics for identifying elementary flux modes?

PLoS One. 2017 Feb 21;12(2):e0171440. doi: 10.1371/journal.pone.0171440. eCollection 2017.

Abstract

We present a method for computing thermodynamically feasible elementary flux modes (tEFMs) using equilibrium constants without need of internal metabolite concentrations. The method is compared with the method based on a binary distinction between reversible and irreversible reactions. When all reactions are reversible, adding the constraints based on equilibrium constants reduces the number of elementary flux modes (EFMs) by a factor of two. Declaring in advance some reactions as irreversible, based on reliable biochemical expertise, can in general reduce the number of EFMs by a greater factor. But, even in this case, computing tEFMs can rule out some EFMs which are biochemically irrelevant. We applied our method to two published models described with binary distinction: the monosaccharide metabolism and the central carbon metabolism of Chinese hamster ovary cells. The results show that the binary distinction is in good agreement with biochemical observations. Moreover, the suppression of the EFMs that are not consistent with the equilibrium constants appears to be biologically relevant.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • CHO Cells
  • Carbon / metabolism
  • Computer Simulation*
  • Cricetinae
  • Cricetulus
  • Metabolic Flux Analysis / methods
  • Metabolic Networks and Pathways / physiology*
  • Models, Biological*
  • Monosaccharides / metabolism
  • Thermodynamics

Substances

  • Monosaccharides
  • Carbon

Grants and funding

The author(s) received no specific funding for this work.