On the validity of the quasi-steady state approximation of bimolecular reactions in solution.
Two-step binding kinetics are extensively used to study the relative importance of diffusion in biochemical reactions. Classical analysis of this problem assumes ad hoc that the encounter complex is at quasi-steady state (QSS). Using scaling arguments we derive a criterion for the validity of this assumption in the limit of irreversible product formation. We find that the QSS approximation (QSSA) of two-step binding is only valid if the total ligand and receptor concentrations are much smaller than (k2+k-1)/k1, where k1 and k-1 are, respectively, the forward and reverse diffusion encounter rate constants and k2 is the chemical association rate constant. This criterion can be shown to imply that the average time between encounters is much longer than the half-life of the encounter complex and also guarantees that the concentration of the encounter complex is negligible compared to the reactant and product concentrations. Numerical examples of irreversible and reversible cases corroborate our analysis and illustrate that the QSS may be invalid even if k-2<<k2. Our analysis of the irreversible case is shown to carry through to the more rigorous framework of the Smoluchowski theory of diffusion-controlled reactions. This work underscores the need for exercising greater caution in invoking the QSSA.
Tzafriri
A Rami
AR
Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Room 16-343, Cambridge, MA 02139, USA. ramitz@mit.edu
Edelman
Elazer R
ER
D000818:Animals; D004058:Diffusion; D004798:Enzymes / Q000493:pharmacokinetics*; D008956:Models, Chemical; D012995:Solubility
D004798:Enzymes