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Cellular metabolism, the integrated interconversion of thousands of metabolic substrates through enzyme-catalyzed biochemical reactions, is the most investigated complex intercellular web of molecular interactions. While the topological organization of individual reactions into metabolic networks is increasingly well understood, the principles governing their global functional utilization under different growth conditions pose many open questions. We implement a flux balance analysis of the E. coli MG1655 metabolism, finding that the network utilization is highly uneven: while most metabolic reactions have small fluxes, the metabolisms activity is dominated by several reactions with very high fluxes. E. coli responds to changes in growth conditions by reorganizing the rates of selected fluxes predominantly within this high flux backbone. The identified behavior likely represents a universal feature of metabolic activity in all cells, with potential implications to metabolic engineering.
An important goal of medical research is to develop methods to recover the loss of cellular function due to mutations and other defects. Many approaches based on gene therapy aim to repair the defective gene or to insert genes with compensatory funct
Metabolic reactions of single-cell organisms are routinely observed to become dispensable or even incapable of carrying activity under certain circumstances. Yet, the mechanisms as well as the range of conditions and phenotypes associated with this b
Understanding the system level adaptive changes taking place in an organism in response to variations in the environment is a key issue of contemporary biology. Current modeling approaches such as the constraint-based flux balance analyses (FBA) have
Understanding the organization of reaction fluxes in cellular metabolism from the stoichiometry and the topology of the underlying biochemical network is a central issue in systems biology. In this task, it is important to devise reasonable approxima
Complex biological systems are very robust to genetic and environmental changes at all levels of organization. Many biological functions of Escherichia coli metabolism can be sustained against single-gene or even multiple-gene mutations by using redu