842 15. EFFECTS OF VARIOUS FACTORS ON INHIBITION 



field of the other reactant. Finally, in enzyme interactions there is always 

 the possibility of alterations in the protein structure, since the active cen- 

 ters of some enzymes appear to be flexible and in other enzymes a certain 

 amount of unfolding or local denaturation may occur upon reaction with 

 the substrates or inhibitors. 



With respect to the contributions of the water to the volume changes, 

 the most important effects are probably due to the changes in the ionic 

 character or polarity of the reactants. A charged group is hydrated and 

 the electric field causes the water molecules to occupy less space than they 

 would if they were free, this being termed electrostriction. The appearance 

 of charged groups thus reduces the solvent volume and the disappearance 

 of charged groups releases water of hydration to increase the solvent 

 volume. Although ionic effects are often dominant, one must also consider 

 the smaller charges associated with dipoles. The electric fields of the 

 reactants may change in quite complex fashion during the formation of the 

 activated complex or the final products and the over-all result will depend 

 on whether there is an increase or decrease in the total polarity. An in- 

 crease of the total polarity in a reaction will constrict the water and a rise 

 in the pressure will thus favor the reaction. Particularly significant volume 

 changes may occur when oppositely charged ionic reactants form a neutral 

 complex, or when a neutral complex breaks down to ionic products. Solvent 

 volume changes may also occur when neutral molecules react, inasmuch 

 as water molecules may be displaced from the nonpolar surfaces and they 

 will be free to enter into the normal water structure, which has somewhat 

 less volume than randomly distributed water molecules. 



The over-all volume change may therefore be made up of many contri- 

 butions, some negative and some positive, but in most simple reactions it 

 is possible to interpret volume changes readily. In reactions occurring in 

 aqueous solution, the major volume changes most commonly relate to the 

 alterations in the water structure. The effects of pressure on the rates 

 of enzyme reactions will, of course, in the general case depend on changes 

 in the binding of the substrate to the enzyme and on the rate of breakdown 

 of the ES complex to products. Thus, both K, (or /i,„) and ko may be altered 

 by pressure. In more complex enzyme reactions, pressure effects may be 

 exerted on different steps in the sequence or on the binding of coenzymes 

 or cofactors to the enzyme. The effects of pressure on enzyme inhibition 

 will be usually more easily interpretable. Excellent discussions of the 

 effects of pressure on enzyme reactions have been presented by Laidler 

 (1958, Chapt. VIII) and Johnson et al. (1954, Chapt. 9). 



Variation of Equilibrium and Rate Constants with Pressure 

 The free energy change for a reaction is given by: 



AF = RTlnK = AE + PAV - TAS (15-105) 



