@article {324101,
	title = {Near-critical phenomena in intracellular metabolite pools.},
	journal = {Biophysical Journal},
	volume = {84},
	number = {1},
	year = {2003},
	month = {2003 Jan},
	pages = {154-70},
	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.},
	keywords = {Biochemical Phenomena, Cell Physiological Phenomena, Enzyme Activation, Enzymes, Homeostasis, Kinetics, Macromolecular Substances, Models, Biological, Models, Chemical, Sensitivity and Specificity, Stochastic Processes, Substrate Specificity},
	issn = {0006-3495},
	doi = {10.1016/S0006-3495(03)74839-5},
	author = {Elf, Johan and Paulsson, Johan and Berg, Otto G and Ehrenberg, M{\r a}ns}
}
