skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Optimal flux patterns in cellular metabolic networks

Journal Article · · Chaos, vol. 17, N/A, June 28, 2007, pp. 026107
DOI:https://doi.org/10.1063/1.2737828· OSTI ID:936992

The availability of whole-cell level metabolic networks of high quality has made it possible to develop a predictive understanding of bacterial metabolism. Using the optimization framework of flux balance analysis, I investigate metabolic response and activity patterns to variations in the availability of nutrient and chemical factors such as oxygen and ammonia by simulating 30,000 random cellular environments. The distribution of reaction fluxes is heavy-tailed for the bacteria H. pylori and E. coli, and the eukaryote S. cerevisiae. While the majority of flux balance investigations have relied on implementations of the simplex method, it is necessary to use interior-point optimization algorithms to adequately characterize the full range of activity patterns on metabolic networks. The interior-point activity pattern is bimodal for E. coli and S. cerevisiae, suggesting that most metabolic reaction are either in frequent use or are rarely active. The trimodal activity pattern of H. pylori indicates that a group of its metabolic reactions (20%) are active in approximately half of the simulated environments. Constructing the high-flux backbone of the network for every environment, there is a clear trend that the more frequently a reaction is active, the more likely it is a part of the backbone. Finally, I briefly discuss the predicted activity patterns of the central-carbon metabolic pathways for the sample of random environments.

Research Organization:
Lawrence Livermore National Laboratory (LLNL), Livermore, CA (United States)
Sponsoring Organization:
USDOE
DOE Contract Number:
W-7405-ENG-48
OSTI ID:
936992
Report Number(s):
UCRL-JRNL-227543; TRN: US200821%%191
Journal Information:
Chaos, vol. 17, N/A, June 28, 2007, pp. 026107, Vol. 17
Country of Publication:
United States
Language:
English

References (33)

Genome-wide analysis of vaccinia virus protein-protein interactions journal April 2000
Minimal Reaction Sets for Escherichia coli Metabolism under Different Growth Requirements and Uptake Environments journal October 2001
Phenotype phase plane analysis using interior point methods journal February 2005
Genome-scale models of microbial cells: evaluating the consequences of constraints journal November 2004
Genome-Scale In Silico Models of E. coli Have Multiple Equivalent Phenotypic States: Assessment of Correlated Reaction Subsets That Comprise Network States journal September 2004
Flux analysis of underdetermined metabolic networks: the quest for the missing constraints journal August 1997
Metabolic gene–deletion strains of Escherichia coli evolve to computationally predicted growth phenotypes journal September 2004
Statistical mechanics of complex networks journal January 2002
Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry journal January 2002
Reconstruction and Validation of Saccharomyces cerevisiae iND750, a Fully Compartmentalized Genome-Scale Metabolic Model journal June 2004
Topological and causal structure of the yeast transcriptional regulatory network journal April 2002
Metabolic flux profiling of Escherichia coli mutants in central carbon metabolism using GC-MS: Metabolic flux profiling in E.���coli journal March 2003
More Is Different journal August 1972
Advances in flux balance analysis journal October 2003
The Activity Reaction Core and Plasticity of Metabolic Networks journal January 2005
Genomic analysis of regulatory network dynamics reveals large topological changes journal September 2004
Computational systems biology journal November 2002
Global organization of metabolic fluxes in the bacterium Escherichia coli journal February 2004
Linear Programming and Extensions book December 1963
BioGRID: a general repository for interaction datasets journal January 2006
Interior Point Algorithms: Theory and Analysis book August 1997
Proteomics to study genes and genomes journal June 2000
A comprehensive two-hybrid analysis to explore the yeast protein interactome journal March 2001
Network motifs in the transcriptional regulation network of Escherichia coli journal April 2002
Formation of Regulatory Patterns During Signal Propagation in a Mammalian Cellular Network journal August 2005
Expansion of the BioCyc collection of pathway/genome databases to 160 genomes journal October 2005
Comparison of network-based pathway analysis methods journal August 2004
The Escherichia coli MG1655 in silico metabolic genotype: Its definition, characteristics, and capabilities journal May 2000
Functional organization of the yeast proteome by systematic analysis of protein complexes journal January 2002
The Human Transcriptome Map: Clustering of Highly Expressed Genes in Chromosomal Domains journal February 2001
Escherichia coli K-12 undergoes adaptive evolution to achieve in silico predicted optimal growth journal November 2002
Chipping away at the transcriptome journal March 2001
A comprehensive analysis of protein–protein interactions in Saccharomyces cerevisiae journal February 2000