294 



VI. HEMOGLOBIN 



interacts reciprocally along F21 with heme 1 and sets up F23 to heme 3. The 

 combination of oxygen witli heme 4 takes place when pathways Fh and F34 

 have already been established, but the reciprocal affects along F41 and F43 



Fig. 13. Heme-heme interaction. 



will lead to a further "settling in" of the oxygen molecule at 1 and 3. It 

 may readily be seen that the result obtained is exactly the same as that 

 obtained by Pauling when he first developed the concept of heme-heme 

 interaction along the four sides of a square. If the interaction is formulated 

 as taking place between both the imidazoles of heme 1 and both imidazoles 

 of heme f2, interaction could only take place between pairs of hemes, since 

 the transmission of the interaction could not be carried to the other hemes. 

 The transmission of a proton shift from one heme to another would be 

 expected to be influenced by constitutional alterations in the molecule, and 

 by the presence of anions bound to the protein. The effect which bicarbonate 

 ion has on the oxygen affinity of hemoglobin, which is relatively greater than 

 that shown by other ions, may be due to the fact that the resonating groups 

 O — C — O form part of the transmission mechanism. The heme-heme 



