JEFFRIES WYMAN, JR. 



for the reaction, and in turn to the interaction constants in accordance 

 with various hypothetical models. 



Another landmark in the interpretation of the oxygen equilibrium 

 curve is due to Pauling, and is based on the extensive data of Ferry 

 and Green on horse haemoglobin. In his analysis Pauling accepted 

 the hypothesis discussed above, though without the evidence presented 

 there, that the four oxygen combining centres in haemoglobin were 

 all alike. He then assumed that they were subject to interactions as if 

 located at the corners of a square, with the same interaction between 

 all adjacent centres but with no interaction between centres situated at 

 the ends of a diagonal. This model leads to a formulation of the 

 oxygen equilibrium involving only one constant controlling the shape 

 of the curve. This is the interaction constant for adjacent centres. 

 The other constant, representing the inherent affinity of a haem for 

 oxygen, simply affects the position of the curve Y vs log p along the 

 log/7 axis. On the basis of this model, by taking the interaction constant 

 as 12 (corresponding to an interaction energy of about 1,500 cals) 

 Pauling found that it was possible to fit the data of Ferry and Green 

 much more exactly than with the Hill equation, in fact, as it appeared, 

 almost if not quite within the experimental error. Since the shape of 

 the curve was independent of pH, it was of course necessary to assume 

 that the interaction constant, unlike the other constant, was unaffected 

 by the dissociation of the oxygen linked acid groups. 



Figure 3. Data of Wyman and Ingalls on 

 oxygen equilibrium of horse haemoglobin in 

 strong urea solutions. The full curve is cal- 

 culated for a molecule containing two identical 

 oxygen combining centres having an interaction 

 constant of 400 corresponding to an interaction 

 energy of 3,550 cals. 



0-4 



0-8 

 Log p 



1-2 



1-6 



It is perhaps disappointing that this remarkably successful hypothesis 

 of Pauling can hardly be retained, at least as it stands. Yet the very 

 objections to it provide an increased insight into the structure of the 

 haemoglobin molecule and suggest a modification of our views which 

 appears to meet the facts, and which accords astonishingly well with 

 conclusions based on quite different considerations. Let us consider 

 these objections. In the first place the Pauling model implies an exactly 



102 



