CHEMICAL PROPERTIES OF SH GROUPS 639 



Many of the atomic and bond properties will be found in the tables of 

 Chapter 1-6. The bond dipole moments are fairly high (C — S 1.73 and S — H 

 0.68, corresponding to fractional atomic charges of 0.20 and 0.11, respec- 

 tively) and the bonds with sulfur are readily polarized (the molar refrac- 

 tions are C — S 4.43, S — H 4.62, and S — S 7.41) compared with most other 

 bonds occurring in proteins. Furthermore, the bond energies are uniformly 

 low compared with the corresponding oxygen bonds, except for the disulfide 

 bond, which is a good deal stronger than the peroxide bond (see accompa- 

 nying tabulation). These fundamental properties account for many of the 



characteristic reactions of the SH group and the relatively unique role of 

 these groups in enzyme activity and inhibitition. The inherent dipole mo- 

 ments and the high polarizability of sulfur bonds may play an important 

 role in the interactions of enzymes with substrates and inhibitors, whereas 

 the bond energies are involved in determining ionization tendencies, oxida- 

 tion-reduction potentials, and the equilibria between SH groups and disul- 

 fide structures. 



The thiol-disulfide equilibria are important for enzyme structure in all 

 probability but, in addition, may well be determining factors in the states 

 and reactivities of the SH groups. It has been shown recently that the reac- 

 tion of a thiol with a disulfide is not a simple oxidation-reduction but an 

 exchange reaction involving a two step ionic displacement (Eldjarn and 

 Pihl, 1957 a, b; Parker and Kharasch, 1959; Foss, 1961), often with the 

 formation of mixed disulfides: 



X— SH + Y— S— S— Y ±^ X— S— S— Y + Y— SH 

 X— S— S— Y -f X— SH ±? X— S— S— X + Y— SH 



Low molecular weight thiols, such as glutathione or cysteine, could thus 

 interact with enzyme SH and disulfide groups to form mixed disulfides. Par- 

 ticularly in the cell, where such thiols occur, these interactions may be im- 

 portant in regulating enzyme activity, and could easily affect the reactivity 

 of enzymes with SH reagents. That this can actually occur with proteins 

 was shown by the use of a colored disulfide, with which seralbumin and /?- 

 lactoglobulin react to form mixed disulfides (Klotz et at., 1958). If an SH 

 enzyme and oxidized glutathione (GSSG) are allowed to react, one would 



