The Intermediate Compound Hypothesis 



in Relation to the Equilibria and Kinetics 



of the Reactions of Haemoglobin with 



Oxygen and Carbon Monoxide 



F. J. W. ROUGHTON 



The various forms of the intermediate compound hypothesis which 

 have appeared in the literature during the past twenty-five years are 

 reviewed in light of the most satisfactory experimental data on the 

 oxyhaemoglobin dissociation curve. Several of the special forms 

 prove to be unserviceable and have to be rejected. A common feature 

 of the remaining is that in each case very little ' interaction ' has to 

 be assumed until three out of four of the 2 or CO molecules have 

 combined. It is then shown how in one such special case, the kinetics 

 of the reactions of combination and dissociation can be rather 

 successfully explained. Further work is, however, needed to see 

 whether the selection of this special case is justified. 



The present paper is devoted to two main objects : 



1 To review the existing position of the intermediate compound 

 hypothesis in regard to the best available dissociation curve data ; 



2 To study further the relation between the empiric equations to 

 which the kinetic data on the haemoglobin reactions conform and 

 the requirements of the intermediate compound hypothesis. 



Not until the kinetics of the reactions as well as the equilibrium are 

 fully interpreted on the intermediate compound hypothesis can the 

 position of the latter be regarded as satisfactory. 



THE INTERMEDIATE COMPOUND HYPOTHESIS IN RELATION 

 TO THE DISSOCIATION CURVE DATA 



According to this hypothesis the general equation for the equilibrium 

 between 2 (or CO) and haemoglobin is given by 



J>_ = K lP + 2K x K 2 p 2 + 3K x K 2 K 3 p* + 4K X K 2 K 3 K^ 

 100 4(1+ K x p + K x K 2 p 2 + K x K 2 K z p* + K X K 2 K Z K^) 



....(1) 



83 



