TY - JOUR T1 - Robustness in Glyoxylate Bypass Regulation A1 - Shinar, Guy A1 - Rabinowitz, Joshua D. A1 - Alon, Uri Y1 - 2009/03/06 N2 - Author Summary To grow well, the cell needs to produce a balanced set of building blocks by means of its metabolic network. Regulatory circuits are used to maintain appropriate fluxes as metabolites flow through the branching pathways in the network. Here, we asked how such regulatory circuits can work precisely, despite the fact that they are made of proteins whose levels vary from cell to cell and in the same cell over time. We used a well-studied circuit, at a key branch point called the glyoxylate bypass, as a model system. Previous experiments showed that this system is remarkably robust to changes in the levels of its proteins. Here, we propose a mechanism to explain this robustness, based on a bifunctional enzyme that catalyzes two opposing reactions. We show that a simple explanation based on enzyme saturation is inconsistent with more rigorous mathematical analysis. Our proposed mechanism suggests several experimentally testable predictions. It shows how a systems-level feature (robustness) may arise from seemingly unrelated biochemical details. Because analogous designs with bifunctional enzymes are found in other systems in different organisms, the present mechanism might apply more broadly. JF - PLOS Computational Biology JA - PLOS Computational Biology VL - 5 IS - 3 UR - https://doi.org/10.1371/journal.pcbi.1000297 SP - e1000297 EP - PB - Public Library of Science M3 - doi:10.1371/journal.pcbi.1000297 ER -