ELIMINATION OF SELF-ASSOCIATION AS THE SOURCE OF THE THERMODYNAMIC NONIDEALITY IN AQUEOUS PROLINE SOLUTIONS

The effect of high concentrations of proline on the diffusion coeffici ent of water has been examined to assess the extent to which the resul ting thermodynamic nonideality could be explained on the statistical-m echanical basis of excluded volume. In fact, such a space-filling role not only accounts for the proline concentration-dependence of the dif fusion coefficient of water but it also accounts for the nonideality o f proline in freezing point depression and isopiestic measurements. Th ese findings refute the conclusion (Schobert, B. and Tschesche, H. (19 78) Biochim. Biophys. Acta 541, 270-277) that the stabilization of enz yme structure by high concentrations of proline stems from self-associ ation of the imino acid via intermolecular hydrogen bonding; and there by support the concept that the protective effect of proline on enzyme stability must reside mainly in its action as an inert, space-filling solute.