The total quasi-steady-state approximation is valid for reversible enzyme kinetics.

The Briggs-Haldane approximation of the irreversible Michaelis-Menten scheme of enzyme kinetics is cited in virtually every biochemistry textbook and is widely considered the classic example of a quasi-steady-state approximation. Though of similar importance, the reversible Michaelis-Menten scheme is not as well characterized. This is a serious limitation since even enzymatic reactions that go to completion may be reversible. The current work derives a total quasi-steady-state approximation (tQSSA) for the reversible Michaelis-Menten and delineates its validity domain. The tQSSA allows the derivation of uniformly valid approximations for the limit of low enzyme concentrations, ET<<ST+KM, and under certain more restrictive conditions also for high enzyme concentrations such that ST<<ET+KM. Using these simple analytical approximations, a sequential experimental-theoretical method is suggested for unambiguously estimating all the kinetic parameters of the reversible Michaelis-Menten scheme.