Metabolic control in integrated biochemical systems.

A. de la Fuente, J.L. Snoep, H.V. Westerhoff, P. Mendes

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Traditional analyses of the control and regulation of steady-state concentrations and fluxes assume the activities of the enzymes to be constant. In living cells, a hierarchical control structure connects metabolic pathways to signal-transduction and gene-expression. Consequently, enzyme activities are not generally constant. This would seem to compromise analyses of control and regulation at the metabolic level. Here, we investigate the concept of metabolic quasi-steady state kinetics as a means of applying metabolic control analysis to hierarchical biochemical systems. We discuss four methods that enable the experimental determination of metabolic control coefficients, and demonstrate these by computer simulations. The best method requires extra measurement of enzyme activities, two others are simpler but are less accurate and one method is bound only to work under special conditions. Our results may assist in evaluating the relative importance of transcriptomics and metabolomics for functional genomics.
Original languageEnglish
Pages (from-to)4399-4408
JournalEuropean Journal of Biochemistry
Volume269
DOIs
Publication statusPublished - 2002

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