A new method for assembling metabolic networks, with application to the Krebs citric acid cycle

Jay E. Mittenthal, Bertrand Clarke, Thomas G. Waddell, Glenn Fawcett

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

To understand why a molecular network has a particular connectivity one can generate an ensemble of alternative networks, all of which meet the same performance criteria as the real network. We have generated alternatives to the Krebs cycle, allowing group transfers and B12-mediated shifts that were excluded in previous work. Our algorithm does not use a reaction list, but determines the reactants and products in generic reactions. It generates networks in order of increasing number of reaction steps. We find that alternatives to the Krebs cycle are very likely to be cycles. Many of the alternatives produce toxic or unstable compounds and use group transfer reactions, which have unfavorable consequences. Although alternatives are better than the Krebs cycle in some respects, the Krebs cycle has the most favorable combination of traits.

Original languageEnglish (US)
Pages (from-to)361-382
Number of pages22
JournalJournal of Theoretical Biology
Volume208
Issue number3
DOIs
StatePublished - Feb 7 2001

ASJC Scopus subject areas

  • Statistics and Probability
  • Modeling and Simulation
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)
  • Agricultural and Biological Sciences(all)
  • Applied Mathematics

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