Regulation of reaction fluxes via enzyme sequestration and co-clustering. Issue 156 (26th July 2019)

• Record Type: Journal Article
• Authors: Hinzpeter, Florian; Tostevin, Filipe; Gerland, Ulrich
• Is Part Of: Journal of the Royal Society interface. Volume 16:Issue 156(2019)
• Publication Date: 2019-07-26
• Subjects: reaction–diffusion dynamics -- metabolic flux regulation -- spatial regulation strategies -- purine biosynthesis pathway; Physical sciences -- Research -- Periodicals; Life sciences -- Research -- Periodicals; Interdisciplinary research -- Periodicals; 570.5
• DOI: 10.1098/rsif.2019.0444
• Languages: English
• ISSNs: 1742-5689

Abstract

Abstract : Experimental observations suggest that cells change the intracellular localization of key enzymes to regulate the reaction fluxes in enzymatic networks. In particular, cells appear to use sequestration and co-clustering of enzymes as spatial regulation strategies. These strategies should be equally useful to achieve rapid flux regulation in synthetic biomolecular systems. Here, we leverage a theoretical model to analyse the capacity of enzyme sequestration and co-clustering to control the reaction flux in a branch of a reaction–diffusion network. We find that in both cases, the response of the system is determined by two dimensionless parameters, the ratio of total activities of the competing enzymes and the ratio of diffusion to reaction timescales. Using these dependencies, we determine the parameter range for which sequestration and co-clustering can yield a biologically significant regulatory effect. Based on the known kinetic parameters of enzymes, we conclude that sequestration and co-clustering represent a viable regulation strategy for a large fraction of metabolic enzymes, and suggest design principles for reaction flux regulation in natural or synthetic systems.