The Haem-Globin Linkage 



183 



conclusive, these studies could indicate the existence of a group of pA!" less 

 than 5-3, if the aetiohaemin is behaving as a weak base (it does not attach to 

 apomyoglobin above pH 8-0) and is acting as an indicator of the ionization 

 of the haem-linked group of the protein. These studies are being extended to 

 apohaemoglobin combination. 



DISCUSSION 



That a change occurs in the acid strength of the haematin propionate 

 groups on reduction of the haematin iron is not unexpected, since it has been 

 well established that variation of the side-chains influences the oxidation- 

 reduction potentials of ferro-ferrihaemochrome systems (Lemberg and 

 Legge, 1949). If alterations to the side-chains can affect the reactions of the 

 iron atom, it is not unreasonable to expect that modifications to the electronic 

 structure of the iron could alter the acid strength of ionizable side-chains. 

 The parallelism between changes of the oxidation-reduction potential at 

 50% oxidation and log/?, where /j is the oxygenation pressure at 50% satura- 

 tion of haemoglobin, with alteration in hydrogen ion concentration, has been 

 clearly demonstrated (Wyman and Ingalls, 1941; see Lemberg and Legge, 

 1949). We may therefore infer that oxygenation affects the acid strength of 

 the propionate groups in much the same way as does oxidation of the iron. 



It was first suggested by Altschul and Hogness (1939) that, on oxygenation, 

 a change occurred in the acid strength of groups of the haem rather than of 

 those of the apoprotein. They considered it very probable that the two 

 carboxyl groups of each haem were influenced by oxygenation. They calcu- 

 lated the pAT values of these carboxyl groups as shown in Table 1. The 



Table 1. Calculated pA" values of haem propionate groups 



IN FERRO- and OXYHAEMOGLOBIN (AlTSCHUL AND HoGNESS, 1939) 



* Temperature unspecified, presumably 25°C. 



actual values may lie somewhere between the extreme values of 5- 5-6-9 

 since the two acid groups may not be altered in an exactly uniform manner, 

 since the dissociation constants may differ as do those of dibasic acids. 

 Examination of the haem structure shows that the vinyl groups at positions 

 2 and 4 give asymmetry, which may mean influence of the propionate at 



