PHILIP GEORGE 



hemoglobin to about 6.7 in oxyhemoglobin (47). The liberation 

 of the proton, which accompanies oxygenation in the pH range 

 between these pK values, accounts for the important physio- 

 logical effect (the Bohr effect) whereby the production of GO2 

 from HCO~3 and CO=3 in the blood is enhanced when hemo- 

 globin becomes oxygenated (32) . Just as the degree of ionization 

 of this acidic group depends upon the extent of oxygenation, so 

 the affinity of the ferrous iron atom for oxygen depends upon 

 the pH of the solution. Groups whose reactions are interde- 

 pendent in this way have been designated "linked groups," and 

 the ionization, a "linked ionization" (47). Evidence has recently 

 been presented showing that the ionization of other groups on 

 the protein as a whole can also influence the reactivity of the 

 heme iron atom, but this effect is perceptible only in solutions 

 of low ionic strength (17). 



Three of the specific hemoprotein reactions are obviously 

 oxidation-reduction processes, and similar considerations are 

 entailed in understanding the specific character of the oxygena- 

 tion reaction, as will be shown later. Yet these specific reactions 

 seem to involve only the iron atom of the heme or hematin, in a 

 valency change, or in replacement reactions at the sixth position 

 in the coordination shell, just like the whole series of nonspecific 

 reactions which hemoproteins undergo. In the ferrous state, 

 for example, combination with carbon monoxide and nitric 

 oxide occurs, and in the ferric state, combination with cyanide, 

 fluoride, azide, thiocyanate, etc. (32). 



A detailed knowledge of the mechanism of these non- 

 specific reactions can therefore help to show how the specificity 

 is achieved in the other reactions, because a comparison of data 

 should enable this specificity to be ascribed to certain thermo- 

 dynamic and kinetic factors. A comparison of this kind would 

 furthermore provide a basis for deciding to what extent hemo- 

 protein reactions conform with those of simpler coordination 

 compounds and aquated ions, and to what extent the especially 

 complicated hemoprotein structure does, in fact, endow the 

 molecule with new properties. 



340 



