Stabilization against thermal inactivation promoted by sugars on enzyme structure and function: Why is trehalose more effective than other sugars?

Trehalose has been described to act as the best stabilizer of structure and function of several macromolecules. Although other sugars also stabilize m acromolecules, none of them are as effective as trehalose. The extraordinar y effect of trehalose has been attributed to several of its properties such as making hydrogen bonds with membranes car the ability to modify the solv ation layer of proteins. However, the explanations always result in a quest ion: Why is trehalose more effective than other sugars? Here, we show that trehalose has a larger hydrated volume than other related sugars. According to our results, trehalose occupies at least 2.5 times larger volume than s ucrose, maltose, glucose, and fructose. We correlate this property with the ability to protect the structure and function of enzymes against thermal i nactivation. When the concentrations of all sugars were corrected by the pe rcentage of the occupied volume, they presented the same effectiveness. Our results suggest that because of this larger hydrated volume, trehalose can substitute more water molecules in the solution, and this property is very close to its effectiveness. Finally, these data drive us to conclude that the higher size exclusion effect is responsible for the difference in effic iency of protection against thermal inactivation of enzymes, (C) 1998 Acade mic Press.