234 



VI. HEMOGLOBIN 



U61, p. 89). Beyond pH 9.5 the heat of dissociation, 11,500 cal., 

 corresponded to that expected for the terminal amino groups of lysine. 



Wyman then investigated the heat of oxygenation of hemoglobin 

 between pH 3 and pH 11 (3135). He says, "the results can be 

 accounted for on the basis of the dissociation of the hydrogen ions 

 which accompanies oxygenation if we assume a heat of dissociation 

 of 6500 calories per equivalent." This value found on horse hemo- 

 globin differed from that found by Roughton on ox hemoglobin (c/., 

 however, Section 3.2.2.4.). 



Wyman interpreted his results in the light of Conant's model by 

 assuming that the iron is situated between two imidazole groups, one 

 of which is displaced when oxygen enters the molecule, with conse- 

 f'uent changes in the ionization of the imidazoles. He attributed the 

 opposite effects, which he found the introduction of oxygen to exert 

 on the ionization on either side of pH 6.4, to the shift of one histidine 

 pK from 5.25 to 5.75 and the other from 7.81 to 6.80, both changes 

 being toward the pK value found for free histidine. Based on 

 Wyman's investigation, Coryell and Pauling (4-99) have given an 

 extremely interesting structural interpretation of the manner in 

 which change of bond type affects the ionization of "oxylabile" 

 groups. A modification of Conant's structure is taken, the heme 

 being assumed to lie between two imidazoles and, after Wyman 

 (3135), closer to one imidazole than to the other. We shall refer to 

 these as the proximal and the distal imidazoles, respectively. Pauling 

 and Coryell (499) discuss first the behavior of the proximal imidazole 

 on the entrj' of oxygen into the molecule in the light of the influence 

 of resonance on acid strength (2125). 



The most important resonance structures assumed to be present 

 are given below: 



N, 



N' 



O2 



Fc' 



N 



.N N. 



^N N' 



Fe 



-N N- 



^N N' 



Fe 



•.N N. 



'N N 



N 



Fe 



N" 



N 



V 



V 



N' 



-v 



H 



A' 



