The Kinetics of Haemoglobin in Solution 

 and in the Red Blood Corpuscle 



F. J. W. ROUGHTON, J. W. LEGGE* and P. NICOLSON 



1 The rate of reaction of X with haemoglobin, where X = 2 

 or CO, has been expressed by the equation d [Z][Hb] jdt = k' 

 [JTj[Hb] - k [X Hb]. At high [X Hb] the equation fails, for k' is 

 now found to rise and k to fall. The discrepancy is explained on the 

 intermediate compound hypothesis. Discrepancies might also occur 

 if haemoglobin at zero time is partially saturated, instead of fully 

 saturated or fully reduced as in most previous work. None were, 

 however, found except in the dissociation of 2 Hb at neutral pH. 

 Here the reaction seems to occur in two phases, the first fast, the 

 second slow. Apparently this effect is largely due to formation of 

 choleglobin and other secondary products, presence of which inter- 

 feres with the photo-electric estimation of haemoglobin saturation. 



2 Mathematical procedures are outlined for investigating the 

 rate of passage of0 2 and CO in and out of a layer of haemoglobin 

 solution, of the same thickness and concentration as the red blood 

 corpuscle, and bounded by a membrane containing no haemoglobin. 

 By these methods, and with new experimental data, it is possible to 

 estimate the permeability of the corpuscle membrane to 2 and CO. 

 The further scope of the work is discussed. 



During the sixteen years before World War II, a large number of 

 observations were reported by H. Hartridge, F. J. W. Roughton and 

 G. A. Millikan 1-11 on the kinetics of the rapid reactions of haemo- 

 globin with oxygen and carbon monoxide. Sir Joseph Barcroft was 

 always deeply interested in this work and, indeed, spent an appreciable 

 part of the last morning of his life in discussing certain aspects of it 

 with the three authors of the present paper. For this reason, as 

 well as for its interest in regard both to special and general problems 

 of haemoglobin, we have felt it not inappropriate to contribute this 

 article to the Barcroft Memorial Conference and Volume. A pre- 

 liminary account of this work was given at the International Congress 

 of Physiology at Oxford in July 1947. 



Work on the kinetics of haemoglobin was almost completely inter- 

 rupted by World War II, and it was not till January 1947 that we were 

 able to take up the subject again in Cambridge. A review of the pre- 

 war work showed that there were many points in the kinetics of haemo- 

 globin, both in solution and in the red blood corpuscle, which had not 

 been fully worked out or understood. During the past 18 months we 



* This work was carried out during the tenure of a Fellowship from the Trustees of the 

 Estate of the late Sir Henry S. Wellcome, to whom J. W. L. wishes to express his thanks. 



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