Extending double modulation: combinatorial rules for identifying the modulations necessary for determining elasticities in metabolic pathways.
The double modulation method for determining the elasticities of pathway enzymes, originally devised by Kacser & Burns (Biochem. Soc. Trans. 7, 1149-1160, 1979), is extended to pathways of complex topological structure, including branching and feedback loops. An explicit system of linear equations for the unknown elasticities is derived. The constraints imposed on this linear system imply that modulations of more than one enzyme are not necessarily independent. Simple combinatorial rules are described for identifying without using any algebra the set of independent modulations that allow the determination of the elasticities of any enzyme. By repeated application, the minimum numbers of modulations required to determine the elasticities of all enzymes of a given pathway can be determined. The procedure is illustrated with numerous examples.
Giersch
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Institut für Botanik der Technischen Hochschule, Darmstadt, Germany. giersch@biol.bio.th-darmstadt.de
Cornish-Bowden
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D000818:Animals; D019295:Computational Biology; D005246:Feedback; D006706:Homeostasis; D008660:Metabolism