%0 Journal Article %J Biophysical Journal %D 2003 %T Near-critical phenomena in intracellular metabolite pools. %A Elf, Johan %A Paulsson, Johan %A Berg, Otto G %A Ehrenberg, Måns %K Biochemical Phenomena %K Cell Physiological Phenomena %K Enzyme Activation %K Enzymes %K Homeostasis %K Kinetics %K Macromolecular Substances %K Models, Biological %K Models, Chemical %K Sensitivity and Specificity %K Stochastic Processes %K Substrate Specificity %X 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. %B Biophysical Journal %V 84 %P 154-70 %8 2003 Jan %G eng %N 1 %1 http://www.ncbi.nlm.nih.gov/pubmed/12524272?dopt=Abstract %R 10.1016/S0006-3495(03)74839-5