1. Department of Physics, University of Notre Dame, Notre Dame, Indiana 46556, USA
2. Biological Physics Department and Research Group of HAS, Eötvös University, H-1117 Budapest, Hungary
3. Department of Pathology, Northwestern University, Chicago, Illinois 60611, USA

Correspondence to: A.-L. Barabási¹ Email: alb@nd.edu

Abstract

Cellular metabolism, the integrated interconversion of thousands of metabolic substrates through enzyme-catalysed biochemical reactions, is the most investigated complex intracellular web of molecular interactions. Although the topological organization of individual reactions into metabolic networks is well understood^{1, 2, 3, 4}, the principles that govern their global functional use under different growth conditions raise many unanswered questions^{5, 6, 7}. By implementing a flux balance analysis^{8, 9, 10, 11, 12} of the metabolism of Escherichia coli strain MG1655, here we show that network use is highly uneven. Whereas most metabolic reactions have low fluxes, the overall activity of the metabolism 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. This behaviour probably represents a universal feature of metabolic activity in all cells, with potential implications for metabolic engineering.

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