Metabolism flows much like city traffic, according to an analysis by Eivind Almaas, Albert-László Barabási (University of Notre Dame, Notre Dame, IN), and colleagues. Although the vast majority of the reactions are less-traveled side roads, a few vital highways carry most of the metabolic traffic.
The organization of the numerous reactions that produces or consumes key metabolites is well-established in E. coli. Metabolites are arranged in a power–law distribution: a large number are made or consumed by only a few reactions, whereas a few metabolites are made or consumed by many more reactions. Barabási's group took a mathematical approach to examine the flux, or the frequency of use, through all of these reactions. Using flux–balance analysis, in which mass conservation, cellular equilibrium, and maximum growth rate constrain the possible flow through each reaction, the authors identified all possible flux states through every reaction for a given growth condition.
They find that, like the metabolite network, flux is also a power–law distribution. Nearly all reactions show low flux. A few, however, channeled the majority of metabolic flux. A similar pattern was found on a local level—when several reactions produced or consumed a given metabolite, most were low flux, whereas one carried most of the burden.
The inequality held true even if maximum growth rate was not assumed or growth conditions changed. “The distribution of flux is the same no matter what environment you have been dumped into,” says Almaas. Traffic is somewhat shifted by new conditions, however, with some high flux pathways changing their flow by orders of magnitude. Low flux pathways change little, if at all. Almaas supposes that flux patterns will be similar for most species since metabolic networks of organisms ranging from yeast to man also show power–law distributions. ▪