Organising metabolic networks: Cycles in flux distributions.

Metabolic networks are among the most widely studied biological systems. The topology and interconnections of metabolic reactions have been well described for many species. This is, however, not sufficient to understand how their activity is regulated in living organisms. These descriptions depict a static set of possible chains of reactions, with no information about the dynamic activity of reaction fluxes. Cyclic structures are thought to play a central role in the homeostasis of biological systems and in their resilience to a changing environment. In this work, we present a methodology to help investigating dynamic fluxes associated to biochemical reactions in metabolic networks. We introduce an algorithm for partitioning fluxes between cyclic and acyclic sub-networks, adapted from an algorithm initially developed to study fluxes in trophic networks. Using this algorithm, we analyse three metabolic systems: the central metabolism of wild type and a deletion mutant of Escherichia coli, erythrocyte metabolism and the central metabolism of the bacterium Methylobacterium extorquens. This methodology unveils the role of cycles in driving and maintaining metabolic fluxes under perturbations in these examples, and may be used to further investigate and understand the organisational invariance of biological systems.

Cyclic decomposition explains a photosynthetic down regulation for Chlamydomonas reinhardtii.

The regulation of metabolic networks has been shown to be distributed and shared through the action of metabolic cycles. Biochemical cycles play important roles in maintaining flux and substrate availability for multiple pathways to supply cellular energy and contribute to dynamic stability. By understanding the cyclic and acyclic flows of matter through a network, we are closer to understanding how complex dynamic systems distribute flux along interconnected pathways. In this work, we have applied a cycle decomposition algorithm to a genome-scale metabolic model of Chlamydomonas reinhardtii to analyse how acetate supply affects the distribution of fluxes that sustain cellular activity. We examined the role of metabolic cycles which explain the down regulation of photosynthesis that is observed when cells are grown in the presence of acetate. Our results suggest that acetate modulates changes in global metabolism, with the pentose phosphate pathway, the Calvin-Benson cycle and mitochondrial respiration activity being affected whilst reducing photosynthesis. These results show how the decomposition of metabolic flux into cyclic and acyclic components helps to understand the impact of metabolic cycling on organismal behaviour at the genome scale.