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Optimality Principles in the Regulation of Metabolic Networks

Systems Bioinformatics, AIMMS, VU University, 1081 HV, Amsterdam, The Netherlands
Kluyver Centre for Genomics of Industrial Fermentation/NCSB, 2600 GA, Delft, The Netherlands
Regulatory Networks Group, Netherlands Institute of Systems Biology, Amsterdam, The Netherlands
Life Sciences, Centre for Mathematics and Computer Science (CWI), 1098 XG Amsterdam, The Netherlands
Author to whom correspondence should be addressed.
Metabolites 2012, 2(3), 529-552;
Received: 20 July 2012 / Revised: 15 August 2012 / Accepted: 17 August 2012 / Published: 29 August 2012
(This article belongs to the Special Issue Metabolism and Systems Biology)
PDF [2889 KB, uploaded 29 August 2012]


One of the challenging tasks in systems biology is to understand how molecular networks give rise to emergent functionality and whether universal design principles apply to molecular networks. To achieve this, the biophysical, evolutionary and physiological constraints that act on those networks need to be identified in addition to the characterisation of the molecular components and interactions. Then, the cellular “task” of the network—its function—should be identified. A network contributes to organismal fitness through its function. The premise is that the same functions are often implemented in different organisms by the same type of network; hence, the concept of design principles. In biology, due to the strong forces of selective pressure and natural selection, network functions can often be understood as the outcome of fitness optimisation. The hypothesis of fitness optimisation to understand the design of a network has proven to be a powerful strategy. Here, we outline the use of several optimisation principles applied to biological networks, with an emphasis on metabolic regulatory networks. We discuss the different objective functions and constraints that are considered and the kind of understanding that they provide. View Full-Text
Keywords: metabolic regulatory networks; optimal regulation; systems biology; design principles metabolic regulatory networks; optimal regulation; systems biology; design principles

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Berkhout, J.; Bruggeman, F.J.; Teusink, B. Optimality Principles in the Regulation of Metabolic Networks. Metabolites 2012, 2, 529-552.

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