Changes in Water Dynamics by Osmolytes Regulate Enzyme Activity.

Area of Science:

• Biochemistry
• Physical Chemistry
• Enzymology

Background:

• Water's critical role in biological functions is recognized, but its molecular dynamics' impact on enzyme activity remains unclear.
• Osmolytes are known to influence biological systems, yet their precise mechanism of action, particularly concerning solvent dynamics, requires further elucidation.

Purpose of the Study:

• To investigate how osmolytes affect enzyme activity by examining the dynamics of surrounding water molecules.
• To establish a correlation between water dynamics, modulated by osmolytes, and the rates of enzymatic reactions.

Main Methods:

• Enzyme activity was measured by monitoring the degradation of amylose by alpha-amylase using visible light absorption.
• Terahertz time-domain spectroscopy was employed to probe the picosecond-scale collective rotational dynamics of water molecules.
• The study analyzed both binary osmolyte-water solutions and ternary enzyme-osmolyte-water systems.

Main Results:

• A direct correlation was found between enzyme activity and water dynamics, independent of the specific osmolyte.
• Osmolytes enhancing water mobility (e.g., urea) accelerated enzymatic reactions.
• Osmolytes restricting water mobility (e.g., sugars, polyols) suppressed enzymatic reactions.

Conclusions:

• Enzyme activity is highly sensitive to picosecond-scale solvent dynamics, suggesting an indirect effect of osmolytes via water modulation.
• Osmolytes likely function as enzyme activity modulators through their influence on water hydration.
• This study provides a framework for understanding osmolyte effects in biological systems by emphasizing the central role of water dynamics in enzymatic catalysis.