Optimal flux patterns in cellular metabolic networks.
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 the 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 has 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 reactions 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.
Almaas
Eivind
E
Biosciences and Biotechnology Division, Lawrence Livermore National Laboratory, Livermore, California 94551, USA. almaas@llnl.gov
D000465:Algorithms; D002244:Carbon / Q000378:metabolism; D002477:Cells / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism; D016480:Helicobacter pylori / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D011382:Programming, Linear; D012441:Saccharomyces cerevisiae / Q000378:metabolism
D002244:Carbon