Applying irreversible thermodynamics to the paradigmatic secondary transporter: lactose permease (LacY)

Lactose permease, a secondary active transporter from Escherichia coli, facilitates the co-transport of protons and lactose across the cytoplasmic membrane. Unlike passive diffusion mechanisms, lactose permease operates via conformational switching that alternately exposes the binding pocket to either membrane side. In this study, we present a theoretical treatment combining irreversible thermodynamic principles and kinetic modeling to quantify its operation. Onsager’s reciprocity is applied to analyze proton-lactose coupling, and a bisubstrate kinetic scheme is employed to simulate system behavior under various proton gradients and lactose concentrations. The complete catalytic cycle is characterized by associated rate constants and energetic transitions, highlighting that lactose permease exhibits a dissipative nature as a hallmark of secondary active transport. Altogether, this study provides a novel thermodynamic perspective on lactose permease, aiming to bridge molecular transport kinetics with the formalism of irreversible processes. This work is the first to integrate Onsager relations with the Michaelis-Menten kinetic model to quantify the energetic efficiency of lactose permease.