Activation entropy, protein denaturation

The activation entropy of the denaturation process is lowered by the isotopic substitution of the solvent (AS (D20) < AS (H20)). It is difficult to see how this could be done other than through solvent effects, since the protein configurational entropy can hardly be affected by replacement of hydrogen by deuterium inside the macromolecule. 

In addition to chemical reactions, the isokinetic relationship can be applied to various physical processes accompanied by enthalpy change. Correlations of this kind were found between enthalpies and entropies of solution (20, 83-92), vaporization (86, 91), sublimation (93, 94), desorption (95), and diffusion (96, 97) and between the two parameters characterizing the temperature dependence of thermochromic transitions (98). A kind of isokinetic relationship was claimed even for enthalpy and entropy of pure substances when relative values referred to those at 298° K are used (99). Enthalpies and entropies of intermolecular interaction were correlated for solutions, pure liquids, and crystals (6). Quite generally, for any temperature-dependent physical quantity, the activation parameters can be computed in a formal way, and correlations between them have been observed for dielectric absorption (100) and resistance of semiconductors (101-105) or fluidity (40, 106). On the other hand, the isokinetic relationship seems to hold in reactions of widely different kinds, starting from elementary processes in the gas phase (107) and including recombination reactions in the solid phase (108), polymerization reactions (109), and inorganic complex formation (110-112), up to such biochemical reactions as denaturation of proteins (113) and even such biological processes as hemolysis of erythrocytes (114). 

An interesting aspect of the photoreaction of PYP is the similarity to the protein folding/unfolding reaction. Hellingwerf and his coworkers applied the transition state theory to the photoreaction of PYP and estimated the thermodynamic parameters, the entropy, enthalpy, and heat capacity changes of activation [29]. They also carried out thermodynamic analysis on the thermal denaturation of PYP. Consequently, they found that the heat capacity changes in the photoreaction are comparable to those in the unfolding... 

The denaturation of proteins is a process in which the whole structure becomes less highly ordered. The rate at which it occurs has an extraordinarily high temperature coefficient which corresponds to an enormous activation energy. This fact is important and shows various things. In the first place, the high value of E points to a not inconsiderable stability of the ordered structure itself. Secondly, the fact that the rate of reaction is not thereby reduced to a low value necessitates the conclusion that the non-exponential factor of the denaturation process is very high. In other words, the entropy of activation is great, so that the transition state is much less ordered... 

We studied the effects of total and partial deuteration on the kinetics of thermal denaturation of met-hemoglobin. The kinetics were shown to be first order with respect to protein concentration this was true both in H2O and in D2O within the entire range of temperatures examined. Deuterium oxide increased the stability of the native conformation of met-hemoglobin this effect increased progressively by increasing the amount of D2O in the solution. Extension of the experiments to the amplest possible temperature range (50-63°C) allowed the determination of the isotopic effect on the activation enthalpy and entropy of the denaturation reaction the isotopic effect resulted to be mainly entropic. 

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