Multisite Enzymes as a Mechanism for Bistability in Reaction Networks

Here, we focus on a common class of enzymes that have multiple substrate binding sites (multisite enzymes) and analyze their capacity to generate bistable dynamics in the reaction networks that they are embedded in. These networks include both substrate- product-substrate cycles and substrate-to-product conversion with subsequent product consumption. Using mathematical techniques, we show that the inherent binding and catalysis reactions arising from multiple substrate-enzyme complexes create a potential for bistable dynamics in such reaction networks. We construct a generic model of an enzyme with n-substrate binding sites and derive an analytical solution for the steady-state concentration of all enzyme-substrate complexes. By studying these expressions, we obtain a mechanistic understanding of bistability, derive parameter combinations that guarantee bistability, and show how changing specific enzyme kinetic parameters and enzyme levels can lead to bistability in reaction networks involving multisite enzymes. Thus, the presented findings provide a biochemical and mathematical basis for predicting and engineering bistability in multisite enzymes.

Automated summary

The study focuses on the capacity of multisite enzymes to generate bistable dynamics in reaction networks, showing that multiple substrate-enzyme complexes have the potential for bistable dynamics. A generic model of an enzyme with n-substrate binding sites is constructed, providing an analytical solution for steady-state concentrations of enzyme-substrate complexes. By analyzing these expressions, mechanisms of bistability are understood and parameter combinations for bistability are derived, demonstrating how specific enzyme kinetic parameters and enzyme levels can influence bistability in multisite enzyme networks.