The Intermediate Compound Hypothesis 



assumption used here, namely that the first three intermediate re- 

 actions occur ' statistically ' and only the final one shows large 

 1 interaction ', is hard to reconcile with the present x-ray crystallo- 

 graphic data on the orientation of the haem groups in crystalline 

 horse oxyhaemoglobin. There are, however, two points to be remem- 

 bered in arguments based on the crystallographic results. / It is 

 possible that the configuration of the molecule may change reversibly 

 when it passes from the dissolved to the crystalline form. 2 No x-ray 

 crystallographic data yet exist on the structure of the reduced haemo- 

 globin or of the orientation of the haem groups therein. All that is 

 known is that the structure is drastically different 13 ' 14 from that of 

 oxyhaemoglobin, methaemoglobin, etc, and it is possible that the 

 same may apply to the orientation of the haem groups. It would 

 therefore seem for the present premature to apply arguments based 

 on x-ray data to equilibria in haemoglobin solution in which oxy- 

 haemoglobin, reduced haemoglobin and compounds of intermediate 

 composition are all present. 



Although it may eventually be found that other special forms of 

 the intermediate compound hypothesis are more successful in com- 

 bined handling of the kinetic, the equilibrium and other data, I hope 

 nevertheless that the treatment given in this paper may prove to be 

 the basis for, or at any rate of aid in providing, the final successful 

 attack, whatever this may be. 



Received September 1948 



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