Changes in Water Dynamics by Osmolytes Regulate Enzyme Activity.

Although water is considered to play a crucial role in biological functions, the relationship between the water's molecular dynamics and enzyme activity has not been systematically clarified. In the present study, we investigated the effects of osmolytes on enzyme activity by focusing on the dynamics of the surrounding water. Degradation of amylose by α-amylase (iodine-starch reaction) was monitored by visible light absorption to determine reaction rates. Terahertz time-domain spectroscopy was used to probe the collective rotational dynamics of water molecules on a picosecond time scale, allowing us to assess changes in water dynamics caused by osmolytes. We identified a clear correlation between enzyme activity and water dynamics beyond the molecular species of osmolytes: osmolytes that enhanced water mobility, such as urea, accelerated enzymatic reactions, whereas those that restricted water mobility, including sugars and polyols, suppressed enzymatic reactions. This correlation was consistently observed not only for osmolyte-water binary solutions but also in enzyme-osmolyte-water ternary systems, strongly implying that osmolytes affect enzyme activity indirectly through modifications of the surrounding water dynamics. These findings provide experimental evidence that enzymatic reactions are highly sensitive to picosecond-scale solvent dynamics. Osmolytes probably function as modulators of enzyme activity through their hydration effects. By highlighting the central role of water dynamics in enzymatic catalysis, this study deepens our understanding of the molecular mechanisms underlying enzyme function and offers a framework for interpreting osmolyte effects in biological systems.