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2403.05507

The Michaelis–Menten reaction at low substrate concentrations: Pseudo-first-order kinetics and conditions for timescale separation

Justin Eilertsen, Santiago Schnell, Sebastian Walcher

correctmedium confidence
Category
Not specified
Journal tier
Specialist/Solid
Processed
Sep 28, 2025, 12:56 AM

Audit review

The paper proves global upper/lower comparisons for the Michaelis–Menten system against linear surrogates G and H and a uniform-in-time O(s0^2) error for the linearization (Proposition 2(d,e)), using Kamke’s comparison theorem and an eigen-expansion/mean-value bound; all assumptions and steps check out (notably, s0 < K is imposed to keep H Hurwitz and the upper bounds viable) . The model’s solution derives the same comparisons and the O(s0^2) error via a different route: positivity of Metzler semigroups and a variation-of-constants convolution estimate yielding an explicit bound |x−x*| ≤ (k1 s0^2/4)(−A^{-1})1, uniform in t. This method is correct and complements the paper’s approach; it also shows the inequalities sup ≥ s ≥ slow and sup ≥ s* ≥ slow hold without needing s0 < K (though the paper restricts to s0 < K to ensure the upper linear system H is stable and practically useful) .

Referee report (LaTeX)

\textbf{Recommendation:} minor revisions

\textbf{Journal Tier:} specialist/solid

\textbf{Justification:}

This work rigorously justifies pseudo-first-order linearization of the Michaelis–Menten system at low substrate, delivering global-in-time comparison bounds and a uniform O(s0\^2) error on compact parameter sets. The theoretical framing via monotone systems and Kamke’s theorem is sound; the results clarify when linearization is valid independent of timescale separation. Minor clarifications on the role of s0 < K and the availability of explicit constants would make the paper even more practical for applications.