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Science 327 (5971): 1389-1391

Copyright © 2010 by the American Association for the Advancement of Science

Structural Sources of Robustness in Biochemical Reaction Networks

Guy Shinar1, and Martin Feinberg2,*

Abstract: 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.

1 Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
2 William G. Lowrie Department of Chemical and Biomolecular Engineering and Department of Mathematics, Ohio State University, 125 Koffolt Laboratories, 140 West 19th Avenue, Columbus, OH 43210, USA.

* To whom correspondence should be addressed. E-mail: feinberg{at}

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