Flux-based hierarchical organization of Escherichia coli's metabolic network

摘要

Metabolism results from the activity of thousands of biochemical reactions, which create, transform and recycle all chemicals, i.e., metabolites, required by life. Metabolic reactions depend on enzymes proteins acting as biological catalyzers to proceed, which effectively links metabolism to other layers in the organization of cellular physiology, such as transcription and translation. These reactions do not operate in isolation but interact in a metabolic network due to the metabolites they share. The joint action of the reactions imposes constraints on the reaction fluxes denoting rates of conversion between metabolites. Here, we identify one such constraint imposed by the metabolic network of E. coli, which we call the flux order relation. Specifically, we identify pairs of reactions in which one reaction always carries a higher flux than the other at steady state. Hence, the flux order relation creates a hierarchical organization of metabolism. We show that the flux order relation is reflected in experimental data sets of fluxes, gene expression, protein levels, and enzyme catalytic constants. Our results point at resource partitioning and a fine-tuning of enzyme levels in E. coli to respect the flux order relation.