Aspects of metabolic regulation can be fruitfully studied with a combination of generic modelling, control analysis and graphical analysis using rate characteristics. This paper analyses a prototypical supply-demand system consisting of a biosynthetic subsystem subject to allosteric inhibition by its product and a demand process that consumes this product. The effect of changes in affinity of the committing supply enzyme for the pathway substrate on the regulatory properties of the supply subsystem is compared for the Monod-Wyman-Changeux and the reversible Hill allosteric enzyme models. We found that the Hill model has a distinct advantage in that the steady-state concentration at which it maintains the product is set by the half-saturating product concentration and is independent of changes in the degree of saturation for substrate. In contrast, with the Monod-Wyman-Changeux model this set point varies with affinity for substrate. Explicitly incorporating reversibility in all rate equations made it possible to distinguish between kinetic and thermodynamic aspects of regulation. Combining the supply and demand rate characteristics allows us to explore both the control distribution at steady state and the regulatory performance of the system over a wide range of demand activities.
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Conference Article|
April 01 2002
The regulatory design of an allosteric feedback loop: the effect of saturation by pathway substrate
S. Hofmeyr Jan-Hendrik;
S. Hofmeyr Jan-Hendrik
1
1Department of Biochemistry, University of Stellenbosch, Private Bag XI, Matieland 7602, South Africa
1To whom correspondence should be addressed (e-mail jhsh@maties.sun.ac.za).
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Brett G. Olivier
Brett G. Olivier
1Department of Biochemistry, University of Stellenbosch, Private Bag XI, Matieland 7602, South Africa
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Publisher: Portland Press Ltd
Received:
November 26 2001
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2002 Biochemical Society
2002
Biochem Soc Trans (2002) 30 (2): 19–25.
Article history
Received:
November 26 2001
Citation
S. Hofmeyr Jan-Hendrik, Brett G. Olivier; The regulatory design of an allosteric feedback loop: the effect of saturation by pathway substrate. Biochem Soc Trans 1 April 2002; 30 (2): 19–25. doi: https://doi.org/10.1042/bst0300019
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