Reaction kinetics in intracellular environments with macromolecular crowding: simulations and rate laws.

We review recent evidence illustrating the fundamental difference between cytoplasmic and test tube biochemical kinetics and thermodynamics, and showing the breakdown of the law of mass action and power-law approximation in in vivo conditions. Simulations of biochemical reactions in non-homogeneous media show that as a result of anomalous diffusion and mixing of the biochemical species, reactions follow a fractal-like kinetics. Consequently, the conventional equations for biochemical pathways fail to describe the reactions in in vivo conditions. We present a modification to fractal-like kinetics following the Zipf-Mandelbrot distribution which will enable the modelling and analysis of biochemical reactions occurring in crowded intracellular environments. Copyright 2004 Elsevier Ltd.