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The conditions for the validity of the standard quasi-steady-state approximation in the Michaelis–Menten mechanism in a closed reaction vessel have been well studied, but much less so the conditions for the validity of this approximation for the system with substrate inflow. We analyze quasi-steady-state scenarios for the open system attributable to singular perturbations, as well as less restrictive conditions. For both settings we obtain distinguished invariant manifolds and time scale estimates, and we highlight the special role of singular perturbation parameters in higher order approximations of slow manifolds. We close the paper with a discussion of distinguished invariant manifolds in the global phase portrait.