The Haem-Globin Linkage 1 87 



a propionate group with a much more basic group, the strength of the com- 

 bination being only shghtly affected on reduction. 



A weak acid-weak base Hnkage would be expected to be considerably 

 affected by neutral salts and specific ions, as is the oxygenation of haemoglobin, 

 while a linkage to a stronger base would be less affected. This concept could 

 explain the effect known as 'haem-haem interaction', and at the same time 

 account for the Bohr effect. That these effects are apparently interrelated is 

 indicated by the loss of both under certain conditions of reconstitution of 

 haemoglobins (Wyman, 1948). Rossi-Fanelli and Antonini (1959) from a 

 study of human deuterohaemoglobin considered the vinyl groups to be 

 involved in 'haem-haem interaction' and illustrated, but did not explain, 

 the influence of removal of these groups in decreasing the Bohr effect at a 

 given pH. The results seem comparable to the findings of Riggs and Wolbach 

 (1956) on addition of mersalyl to horse haemoglobin. In both cases these 

 effects would appear to be secondary, in the first from a decrease in acid 

 strength of the haem propionates, brought about by removal of the vinyl 

 groups; in the second on account of the propionate binding group of the 

 protein becoming more basic, through combination of a neighbouring 

 sulphydryl group with the mersalyl. 



A labile electrostatic linkage between at least one of the two haem pro- 

 pionates of each of the four haems and imidazolium side-chains of the 

 apoprotein might explain, better than 'haem-haem interaction', the sigmoid 

 oxygen dissociation curve and the Bohr effect in horse haemoglobin. Linkage 

 to more or less basic groups than the imidazoliums of horse haemoglobin 

 could conceivably explain the curves for other species, including those with 

 'atypical' curves. The detachment of the propionates in ferrohaemoglobins 

 could explain the change in molecular shape on deoxygenation and also 

 partly account for dry oxyhaemoglobin not releasing oxygen at low oxygen 

 pressures (Haurowitz and Hardin, 1954), the electrostatic bond breaking only 

 in solution. 



While the exact state of the haemoglobin in the erythrocyte is unknown 

 (see Wintrobe, 1956), the most likely condition — attachment to a framework 

 of stromatin at an equivalent concentration of 34 % haemoglobin — could be 

 conceived as decreasing the velocity of diffusion of oxygen into the interior 

 of the cell. A change in shape of the haemoglobin molecules on breaking the 

 electrostatic link might counteract this to some extent by 'agitation' of the 

 cell contents. 



SUMMARY 



1. Reduction of haematin to haem markedly decreases the acid strength 

 of one or (more probably) both of the propionate side-chains. 



2. Nickel mesoporphyrin which can only combine through its propionate 

 side-chains, links with a group or groups in horse apohaemoglobin v/ith 

 imidazolium characteristics. 



H.E. — VOL. I — o 



