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Steady-State Kinetics of the Autocatalytic Zymogen Activation: A Comparison with the Michaelis-Menten Reaction Mechanism

preprint
revised on 18.11.2019 and posted on 27.11.2019 by Malgorzata Tyczynska, Justin Eilertsen, Santiago Schnell

A zymogen is an inactive precursor of an enzyme, which needs to go through a chemical change to become an active enzyme. The general intermolecular mechanism for the autocatalytic activation of zymogens is governed by the single-enzyme, single-substrate catalyzed reaction following the Michaelis-Menten mechanism of enzyme action, where the substrate is the zymogen and product is the same enzyme catalyzing the reaction. In this article we investigate the nonlinear chemical dynamics of the intermolecular autocatalytic zymogen activation reaction mechanism, and compare it to that of the Michaelis-Menten reaction mechanism. We show that the intermolecular autocatalytic zymogen activation exhibits significant changes in reaction dynamics relative to the Michaelis-Menten reaction mechanism. These changes include differences in the number of conservation laws, number and stability of equilibrium states, altered structure of the invariant set that influences the long-time rate of the reaction, and qualitative evolution of the reaction depending strictly on the choice of initial conditions. We find a rate law, homologous to the Michaelis-Menten equation, to estimate the kinetic parameters of the intermolecular autocatalytic zymogen activation reaction mechanism, and derive the conditions for the validity for this rate law. Finally, we derive analytical expressions to estimate the timescale for the completion of the zymogen activation, which could have a practical application to calculate the molar enthalpy of the autocatalytic zymogen reaction in calorimetry assays.

Funding

Justin Eilertsen is supported by NIH/NIDDK K12 DK071212

History

Email Address of Submitting Author

schnells@umich.edu

Institution

University of Michigan Medical School

Country

USA

ORCID For Submitting Author

0000-0002-9477-3914

Declaration of Conflict of Interest

No conflict of interest to declare.

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