Identifying and characterising regulatory metabolites with generalised supply-demand analysis

Date
2008
Authors
Rohwer J.M.
Hofmeyr J.-H.S.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
We present the framework of generalised supply-demand analysis (SDA) of a kinetic model of a cellular system, which can be applied to networks of arbitrary complexity. By fixing the concentrations of each of the variable species in turn and varying them in a parameter scan, rate characteristics of supply-demand are constructed around each of these species. By inspecting the shapes of the rate characteristic patterns and comparing the flux-response coefficients of the supply and demand blocks with the elasticities of the enzymes that interact directly with the fixed metabolite, regulatory metabolites in the system can be identified and characterised. The analysis provides information on whether and where the system is functionally differentiated and which of its species are homeostatically buffered. The novelty in our proposed method lies in the fact that all metabolites are considered for SDA (hence the term "generalised"), which removes investigator bias. It supplies an entry point for the further analysis and detailed characterisation of large models of cellular systems, in which the choice of metabolite around which to perform a SDA is not always obvious. © 2007 Elsevier Ltd. All rights reserved.
Description
Keywords
bioenergetics, cytology, elasticity, enzyme activity, homeostasis, metabolite, reaction kinetics, article, cell function, concentration (parameters), conceptual framework, homeostasis, kinetics, metabolic regulation, metabolite, priority journal, protein interaction, quantitative analysis, statistical model, Animals, Computational Biology, Elasticity, Homeostasis, Metabolic Networks and Pathways, Models, Biological, Systems Biology
Citation
Journal of Theoretical Biology
252
3