Designing metabolism: Alternative connectivities for the pentose phosphate pathway

Jay E. Mittenthal, Ao Yuan, Bertrand Clarke, Alexander Scheeline

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Abstract

We present a method for generating alternative biochemical pathways between specified compounds. We systematically generated diverse alternatives to the nonoxidative stage of the pentose phosphate pathway, by first finding pathways between 5-carbon and 6-carbon skeletons. Each solution of the equations for the stoichiometric coefficients of skeleton-changing reactions defines a set of networks. Within each set we selected networks with modules; a module is a coupled set of reactions that occurs more than one in a network. The networks can be classified into at least 53 families in at least seven superfamilies, according to the number, the input-output relations, and the internal structure of their modules. We then assigned classes of enzymes to mediate transformations of carbon skeletons and modifications of functional groups. The ensemble of candidate networks was too large to allow complete determination of the optimal network. However, among the networks we studied the real pathway is especially favorable in several respects. It has few steps, uses no reducing or oxidizing compounds, requires only one ATP in one direction of flux, and does not depend on recurrent inputs.

Original languageEnglish (US)
Pages (from-to)815-856
Number of pages42
JournalBulletin of Mathematical Biology
Volume60
Issue number5
DOIs
Publication statusPublished - Sep 1998

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ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology
  • Mathematics(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Environmental Science(all)
  • Pharmacology
  • Agricultural and Biological Sciences(all)
  • Computational Theory and Mathematics

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