Structural sources of robustness in biochemical reaction networks.
In vivo variations in the concentrations of biomolecular species are inevitable. These variations in turn propagate along networks of chemical reactions and modify the concentrations of still other species, which influence biological activity. Because excessive variations in the amounts of certain active species might hamper cell function, regulation systems have evolved that act to maintain concentrations within tight bounds. We identify simple yet subtle structural attributes that impart concentration robustness to any mass-action network possessing them. We thereby describe a large class of robustness-inducing networks that already embraces two quite different biochemical modules for which concentration robustness has been observed experimentally: the Escherichia coli osmoregulation system EnvZ-OmpR and the glyoxylate bypass control system isocitrate dehydrogenase kinase-phosphatase-isocitrate dehydrogenase. The structural attributes identified here might confer robustness far more broadly.
Shinar
Guy
G
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
Feinberg
Martin
M
D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism*; D001426:Bacterial Proteins / Q000378:metabolism*; D004926:Escherichia coli / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000378:metabolism*; D006038:Glyoxylates / Q000378:metabolism; D007521:Isocitrate Dehydrogenase / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D008956:Models, Chemical; D009097:Multienzyme Complexes / Q000378:metabolism*; D009994:Osmolar Concentration; D010766:Phosphorylation; D015398:Signal Transduction; D015534:Trans-Activators / Q000378:metabolism*
D001425:Bacterial Outer Membrane Proteins; D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D006038:Glyoxylates; D009097:Multienzyme Complexes; D015534:Trans-Activators; C112177:osmolarity response regulator proteins; C548023:AceK protein, E coli; D007521:Isocitrate Dehydrogenase; C057843:envZ protein, E coli; C031150:glyoxylic acid