ON THE STABILITY OF OXYHAEMOGLOBIN 



By J. H. Wang 



Sterling Chemistry Laboratory, Yale University, Connecticut 



It is well known that in the absence of oxygen, haem and haemochromes 

 combine reversibly with carbon monoxide. But these carbon-monoxyhaem 

 compounds are rapidly oxidized when their aqueous solutions are exposed 

 to air. By analogy it is generally inferred that free haem also combines with 

 molecular oxygen, but the resulting 'oxyhaem' is so unstable in aqueous 

 solutions that it immediately goes over to the Fe+++-state. 



Previous infra-red and magnetic studies (Wang, Nakahara and Fleischer, 

 1958) show that there is no detectable difference in the nature of the primary 

 valence which binds the carbon monoxide molecule to haemoglobin and haem 

 respectively. Quantitative equilibrium measurements show that the standard 

 free energy of formation, AF°, of carbonmonoxyhaem from carbon monoxide 

 and haem is only about 2 kcal/mole higher than that of carboxy haemoglobin. 

 This value is clearly too small to account for the much greater resistance of 

 oxyhaemoglobin and carboxyhaemoglobin toward oxidation by molecular 

 oxygen as compared to 'oxyhaem' and carbonmonoxyhaem respectively. In 

 fact the standard free energy of formation of the complex pyridine-haem- 

 carbon monoxide is even closer to that of carboxyhaemoglobin (Nakahara 

 and Wang, 1958). 



On the other hand, one could attempt to attribute the stability of oxyhaemo- 

 globin to the greater stability of the Fe++-state (relative to the Fe+++-state) 

 in haemoglobin as compared to that in free haem. For example, at pH 8 

 and 25°C the standard potential of the couple 



methaemoglobin + Ae" :^ haemoglobin 



is 0-3 V higher than that for the couple 



ferrihaem + e~ ^ haem 



(Barron, 1937; Havemann, 1943). However, the standard potential of the 

 couple 



dipyridine ferrihaemochrome + e~ :^ dipyridine ferrohaemochrome 



IS about the same as that of haemoglobin, and yet it is a known fact that 

 aqueous solutions of haemochromes, whether in monomeric form or 



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