Essentiality and damage in metabolic networks

Bioinformatics. 2004 Jan 1;20(1):115-9. doi: 10.1093/bioinformatics/btg386.

Abstract

Understanding the architecture of physiological functions from annotated genome sequences is a major task for postgenomic biology. From the annotated genome sequence of the microbe Escherichia coli, we propose a general quantitative definition of enzyme importance in a metabolic network. Using a graph analysis of its metabolism, we relate the extent of the topological damage generated in the metabolic network by the deletion of an enzyme to the experimentally determined viability of the organism in the absence of that enzyme. We show that the network is robust and that the extent of the damage relates to enzyme importance. We predict that a large fraction (91%) of enzymes causes little damage when removed, while a small group (9%) can cause serious damage. Experimental results confirm that this group contains the majority of essential enzymes. The results may reveal a universal property of metabolic networks.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Enzyme Activation
  • Enzyme Stability
  • Enzymes / chemistry*
  • Enzymes / classification
  • Enzymes / deficiency
  • Enzymes / metabolism*
  • Escherichia coli / enzymology*
  • Metabolism / physiology*
  • Models, Biological*
  • Multienzyme Complexes / chemistry*
  • Multienzyme Complexes / classification
  • Multienzyme Complexes / deficiency
  • Multienzyme Complexes / metabolism*
  • Mutation
  • Structure-Activity Relationship

Substances

  • Enzymes
  • Multienzyme Complexes