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Molecular noise-induced activator-inhibitor duality in enzyme inhibition kinetics

, Manmath Panigrahy
Published in Americal Institute of Physics
2023
Volume: 159
   
Pages: 155101-1 - 155101-14
Abstract

Classical theories of enzyme inhibition kinetics predict a monotonic decrease in the mean catalytic activity with the increase in inhibitor concentration. The steady-state result, derived from deterministic mass action kinetics, ignores molecular noise in enzyme-inhibition mech- anisms. Here, we present a stochastic generalization of enzyme inhibition kinetics to mesoscopic enzyme concentrations by systematically accounting for molecular noise in competitive and uncompetitive mechanisms of enzyme inhibition. Our work reveals an activator-inhibitor duality as a non-classical effect in the transient regime in which inhibitors tend to enhance enzymatic activity. We introduce statistical measures that quantify this counterintuitive response through the stochastic analog of the Lineweaver–Burk plot that shows a merging of the inhibitor-dependent velocity with the Michaelis–Menten velocity. The statistical measures of mean and temporal fluctuations - fractional enzyme activity and waiting time correlations - show a non-monotonic rise with the increase in inhibitors before subsiding to their baseline value. The inhibitor and substrate dependence of the fractional enzyme activity yields kinetic phase diagrams for non-classical activator-inhibitor duality. Our work links this duality to a molecular memory effect in the transient regime, arising from positive correlations between consecutive product turnover times. The vanishing of memory in the steady state recovers all the classical results.

About the journal
JournalJournal of Chemical Physics
PublisherAmerical Institute of Physics
Open AccessNo