Abstract
Enzyme performance parameters, including the turnover number and specificity constant, exhibit remarkable diversity due to biological evolution and natural selection. In some bacterial and human enzymes, catalytic efficiencies approach fundamental physical limits, underscoring the importance of physical constraints on enzymatic function. A deeper understanding of these constraints, particularly in far-from-equilibrium irreversible processes, is therefore essential for rational enzyme engineering. Such constraints are most naturally addressed within the frameworks of nanothermodynamics and stochastic thermodynamics, which remain relatively unfamiliar to much of the molecular biology community. Recent theoretical and experimental advances indicate that classical enzyme kinetic parameters are not independent, but are systematically linked to energetic dissipation. In particular, enzymes appear to occupy a characteristic dissipation plane defined by entropy production, reflecting the coupled influence of thermodynamic principles and evolutionary selection. In this review, we synthesize evidence across diverse enzyme families demonstrating correlated increases in housekeeping dissipation, evolutionary divergence, and enzymatic performance. Together, these findings support dissipation as a physically grounded parameter that connects enzyme kinetics, biological evolution, and nonequilibrium thermodynamics.