title: Near-critical phenomena in intracellular metabolite pools.
abstract: The supply and consumption of metabolites in living cells are catalyzed by enzymes. Here we consider two of the simplest schemes where one substrate is eliminated through Michaelis-Menten kinetics, and where two types of substrates are joined together by an enzyme. It is demonstrated how steady-state substrate concentrations can change ultrasensitively in response to changes in their supply rates and how this is coupled to slow relaxation back to steady state after a perturbation. In the one-substrate system, such near-critical behavior occurs when the supply rate approaches the maximal elimination rate, and in the two-substrate system it occurs when the rates of substrate supply are almost balanced. As systems that operate near criticality tend to display large random fluctuations, we also carried out a stochastic analysis using analytical approximations of master equations and compared the results with molecular-level Monte Carlo simulations. It was found that the significance of random fluctuations was directly coupled to the steady-state sensitivity and that the two substrates can fluctuate greatly because they are anticorrelated in such a way that the product formation rate displays only small variation. Basic relations are highlighted and biological implications are discussed.
authors.affiliation: Department of Cell & Molecular Biology, Uppsala University, BMC, Sweden. johan.elf@icm.uu.se
authors.forename: Johan
authors.initials: J
authors.lastname: Elf
authors.forename: Johan
authors.initials: J
authors.lastname: Paulsson
authors.forename: Otto G
authors.initials: OG
authors.lastname: Berg
authors.forename: Måns
authors.initials: M
authors.lastname: Ehrenberg
mesh_terms: D001669:Biochemical Phenomena; D002468:Cell Physiological Phenomena; D004789:Enzyme Activation; D004798:Enzymes / Q000737:chemistry* / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology; D007700:Kinetics; D046911:Macromolecular Substances; D008954:Models, Biological; D008956:Models, Chemical; D012680:Sensitivity and Specificity; D013269:Stochastic Processes; D013379:Substrate Specificity
chemical_list: D004798:Enzymes; D046911:Macromolecular Substances