Which Metabolic Pathways Generate and Characterize the Flux Space? A Comparison among Elementary Modes, Extreme Pathways and Minimal Generators

Important efforts are being done to systematically identify the relevant pathways in a metabolic network. Unsurprisingly, there is not a unique set of network-based pathways to be tagged as relevant, and at least four related concepts have been proposed: extreme currents, elementary modes, extreme pathways, and minimal generators. Basically, there are two properties that these sets of pathways can hold: they can generate the flux space-if every feasible flux distribution can be represented as a nonnegative combination of flux through them-or they can comprise all the nondecomposable pathways in the network. The four concepts fulfill the first property, but only the elementary modes fulfill the second one. This subtle difference has been a source of errors and misunderstandings. This paper attempts to clarify the intricate relationship between the network-based pathways performing a comparison among them.