Deterministic and Stochastic Models in Enzyme Kinetics

Enzyme kinetics has historically been described by deterministic models, with the Michaelis-Menten (MM) equation serving as a paradigm. However, recent experimental and theoretical advances have made it clear that stochastic fluctuations, particularly at low copy numbers or single-enzyme levels, can profoundly impact reaction outcomes. In this paper, we present a comprehensive view of enzyme kinetics from both deterministic and stochastic perspectives. We begin by deriving the classical Michaelis-Menten equation under the quasi-steady-state assumption (QSSA) and discuss its validity. We then formulate the corresponding stochastic model via the chemical master equation (CME) and illustrate how the Gillespie algorithm can simulate single-molecule events and briefly use Kampen's system-size expansion to justify our simulation methods. Through extended computational analyses -- including variance calculations, phase-plane exploration, and parameter sensitivity -- we highlight how deterministic and stochastic predictions coincide in certain limits but can diverge in small systems. We further incorporate case studies from single-enzyme turnover experiments and cellular contexts to showcase the real-world implications of noise. Taken together, our results underscore the necessity of a multifaceted modeling strategy, whereby one can switch between deterministic methods and stochastic realism to gain a fuller understanding of enzyme kinetics at different scales.

Jiaji Qu, Malini Rajbhandari · 2025