The quasi-steady-state approximation is widely used to develop simplified deterministic or stochastic models of enzyme catalyzed reactions. In deterministic models, the quasi-steady-state approximation can be mathematically justified from singular perturbation theory. For several closed enzymatic reactions, the homologous extension of the quasi-steady-state approximation to the stochastic regime, known as the stochastic quasi-steady-state approximation, has been shown to be accurate under the analogous conditions that permit the quasi-steady-state reduction in the deterministic counterpart. However, it was recently demonstrated that the extension of the stochastic quasi-steady-state approximation to an open Michaelis-Menten reaction mechanism is only valid under a condition that is far more restrictive than the qualifier that ensures the validity of its corresponding deterministic quasi-steady-state approximation. In this paper, we suggest a possible explanation for this discrepancy from the lens of geometric singular perturbation theory. In so doing, we illustrate a misconception in the application of the quasi-steady-state approximation: timescale separation does not imply singular perturbation.
Keywords: Fenichel theory; Langevin equation; Linear noise approximation; Michaelis–Menten reaction mechanism; Quasi-steady-state approximation; Singular perturbation; Slow scale linear noise approximation; Stochastic process; Tikhonov’s theorem.
© 2021. The Author(s), under exclusive licence to Society for Mathematical Biology.