Maximum Entropy Production Theorem for Transitions between Enzyme Functional States and Its Applications

Area of Science:

• Biochemistry
• Thermodynamics
• Enzyme kinetics

Background:

• Enzyme functional state transitions involve conformational changes, atomic movements, and transport processes.
• These fluxes are driven by non-equilibrium substrate and product concentrations, leading to entropy production.
• Maximal transitional entropy production (MTEP) is a theoretical concept, but its direct link to increased total entropy production and enzyme performance is not always guaranteed.

Purpose of the Study:

• To investigate the conditions under which total entropy production increases alongside enhanced enzyme or bioenergetic system performance.
• To explore the applicability of the MTEP theorem in understanding enzyme functional state transitions.
• To identify rate-limiting steps in catalytic cycles and optimize them for efficiency.

Main Methods:

• Application of the MTEP theorem to specific enzymes: triosephosphate isomerase, ATP synthase, and β-lactamases.
• Analysis of the photochemical cycle of bacteriorhodopsin.
• Identification of rate-limiting steps based on free-energy dissipation and catalytic efficiency.

Main Results:

• MTEP requirements do not automatically ensure increased total entropy production or catalytic performance.
• Rate-limiting steps are identified as those most efficient in dissipating free-energy gradients and performing catalysis.
• The final step in catalytic cycles often involves significant free-energy dissipation, particularly through proton currents, and can be optimized using MTEP.

Conclusions:

• Biological evolution towards optimal catalytic efficiency is coupled with accelerated thermodynamic evolution.
• The 'evolution-coupling hypothesis' describes this synergistic relationship between catalytic and thermodynamic advancements.
• Optimizing rate-limiting steps, especially the final recovery step involving proton currents, can enhance enzyme efficiency through MTEP principles.