Impact of enzyme turnover on the dynamics of the Michaelis-Menten model (Q2137774)

The authors continue their investigations on the open Michaelis-Menten enzyme system begun in reference [\textit{J. Gabrielsson} and \textit{L. Peletier}, ``Michaelis-Menten from an in vivo perspective: open versus closed systems'', AAPS Journal 20, Paper No. 102, 13 p. (2018; \url{doi:10.1208/s12248-018-0256-z})]. In the closed system, the total pool of enzyme, free and bound, is constant. Inserting synthesis and degeneration of enzyme (enzymatic turnover) into the model leads to the open version. This model is closer to what happens in vivo, where proteins are steadily synthesized and eliminated. It also allows to keep track of the development over time after constant and after bolus supply of substrate. Various details of the open system are uncovered. An example is the fact that the maximal substrate value turns out to depend quadratically on the infusion rate. Also, the effect of the rates of enzyme turnover and of catalysis on the dynamics of the open system is discussed, and the limit behavior of the open system to the closed one if the turnover tends to zero is studied. Graphical simulation diagrams illustrate numerous results.