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10 - Sensitivity Analysis in Metabolic Processes

Published online by Cambridge University Press:  04 May 2010

Arvind Varma
Affiliation:
University of Notre Dame, Indiana
Massimo Morbidelli
Affiliation:
ETH Zentrum, Switzerland
Hua Wu
Affiliation:
Ausimont Research and Development Center, Italy
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Summary

In the recent decades, growth in molecular biology has been explosive. The details of molecular constituents and of chemical transformations in metabolism have become increasingly clear, at least for a number of simpler organisms. An important strategy for molecular biologists is to reduce a complex biochemical reacting system to its elemental units, in order to explain it at the molecular level, and then to use this knowledge to reconstruct it. However, cellular components exhibit large interactions that are associative rather than additive. We still know relatively little about such interactions, what makes such an integrated system a living cell, and how a reconstructed system will respond to variations in novel environments and to specific variations in the metabolic pathway. To understand them, molecular biologists now recognize the need for systematic methods that can be provided by mathematical analysis.

As an effective mathematical tool, sensitivity analysis has been widely applied in biochemical reacting systems in order to understand the effects of variations in activities of enzymes, in kinetic parameters, and in external modifiers on metabolic processes. In other words, the objective is to understand how the function of an integrated biochemical system can be deduced from kinetic observations of its elemental units. The applications of sensitivity analysis in biochemical reacting systems were pioneered by Higgins (1963) and have spawned three basic theories: biochemical systems theory (Savageau, 1969a,b,c, 1971a,b, 1976), metabolic control theory (Kacser and Burns, 1973; Heinrich and Rapoport, 1974a,b; Westerhoff and Chen, 1984; Fell and Sauro, 1985; Reder, 1988; Giersch, 1988), and flux-oriented theory (Crabtree and Newsholme, 1978, 1985, 1987).

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Publisher: Cambridge University Press
Print publication year: 1999

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