Foetal Haemoglobin and Rh. Antagonisms 



At/?H 11-7 the haemoglobin of an adult denatures slowly. Under 

 this condition it becomes evident that the haemoglobin of adult men 

 is made up of two different fractions having slightly different resistances 

 to alkali {Figure 3). Because the difference in denaturation rate 

 between the two haemoglobins in the blood of human adults is only 

 slight, the angle between the two lines representing the different rates 

 of denaturation is small. The possibility must be considered that this 

 phenomenon is the result of a secondary reaction. To exclude this 

 possibility I stopped the reaction after six minutes. At this time 

 nearly all haemoglobin of the less resistant fraction had been de- 

 natured. The denaturation-product, alkaline-globin-haemochromogen, 

 was precipitated and the remaining undenatured haemoglobin was 

 concentrated. This haemoglobin solution should contain only the 

 more resistant fraction, and this proved to be the case. 



The occurrence of two different haemoglobins in adults has also 

 been demonstrated by others. R. Brinkman 7 determined the per- 

 centage of these two fractions in his own blood every day for a month 

 or more. It seems that the fraction which is slightly more resistant 

 is at times nearly absent. Subsequently over a period of a few weeks 

 its percentage increases slowly up to about 50 per cent ; after that it 

 once more gradually diminishes. 



Although little is known about these different haemoglobins in 

 adult men, more is known about the differences between foetal and 

 later haemoglobin. There is an interesting difference between the 

 behaviour of later and foetal haemoglobin when spread in a mono- 

 molecular layer on the surface of water in a trough 8 ' 9 . When the 

 pH of the water is about the iso-electric point of the haemoglobin 

 (concentration of the buffer solution : 3 millimolar) the later haemo- 

 globin rapidly forms a stable monomolecular layer with a thickness of 

 about 8A. Foetal haemoglobin forms a stable layer but far more 

 slowly, taking about 10 minutes to spread completely. In other words 

 the molecule of foetal haemoglobin unfolds itself more slowly than 

 the later form. The nature of the differences between foetal and later 

 haemoglobin is uncertain, but is known to lie in the protein com- 

 ponents (i.e. the globins). A comparison of some of the properties 

 of foetal and later haemoglobin of different species throws some light 

 on the nature of these differences. In human beings foetal haemo- 

 globin is more resistant to alkali and unfolds itself more slowly to a 

 monomolecular layer ; furthermore the oxygen dissociation curve of 

 foetal haemoglobin is shifted to the right of the adult curve. 



In most animals (e.g. goat, sheep, cow) the relation is just the 

 opposite. In the sheep, goat and cow foetal haemoglobin is less 

 resistant to alkali, the molecule unfolds itself more rapidly to a mono- 



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