On the validity of the stochastic quasi-steady-state approximation in open enzyme catalyzed reactions: Timescale separation or singular perturbation?


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 of 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 explain this discrepancy through the rigorous application of geometric singular perturbation theory. In so doing, we illustrate a common misconception in the application of the quasi-steady-state approximation: a problem which involves timescale separation is not always a singular perturbation problem.

ARXIV, 2103.10566 [math.DS]