Dynamic disorder-driven substrate inhibition and bistability in a simple enzymatic reaction.

Conformations and catalytic rates of enzymes (biological catalysts) fluctuate over a wide range of time scales. Recent experimental and theoretical investigations demonstrated case studies where the enzymatic catalysis rate follows the Michaelis-Menten (MM) rate law despite molecular fluctuations. In this paper, we investigate deviations from MM law and their effects on the dynamical behavior of the enzymatic network. We consider a simple kinetic scheme for a single substrate enzymatic reaction in which the product release step is treated explicitly. We examine how conformational fluctuations affect the underlying rate law in the quasi-static limit when conformational dynamics is very slow in one of the states. Our numerical results and analytically solvable model indicate that slow conformational fluctuations of the enzyme-substrate complex lead to non-MM behavior, substrate inhibition, and possible bistability of the reaction network.