The thalassaemia syndromes / D.J. Weatherall.

  • Weatherall, D. J.
Date:
1972
Catalogue details

Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: The thalassaemia syndromes / D.J. Weatherall. Source: Wellcome Collection.

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    20 THE THALASSAEMIA SYNDROMES most mammalian red cells, is specifically bound to deoxyhaemoglobin in the relationship of one molecule per haemoglobin tetramer (Benesch and Benesch, 1969). The binding of oxygen and DPG is mutually exclusive and the oxygenation of haemoglobin in the presence of DPG can be written Hb. DPG + O2 ^Hb02 + DPG In energetic terms this means that there is a decrease in oxygen afl&nity as the concentration of DPG increases. Perutz (1970) has suggested that with haemoglobin in the deoxygenated form, DPG fits into the positively charged cavity between the N-termini of the /S-chains. On oxygenation this binding site closes so accounting for the observed interactions between oxyhaemoglobin, deoxyhaemoglobin and DPG. It is clear, therefore, that the level of DPG is critical in determining the oxygen affinity. It seems likely that the differences in oxygen affinity between foetal and adult blood depend on the differential binding of DPG with foetal as compared with adult haemoglobin. Other situations where the interaction between DPG and haemoglobin is of particular importance include the change in oxygen affinity which follows prolonged storage of blood, the adaptive changes which occur with increasing altitude, and the relationship of sodium transport across the red cell membrane to the oxygenation of haemoglobin. This is the subject of an excellent review by Benesch and Benesch (1969). In addition to its role of oxygen carrier, haemoglobin is also responsible for the transport of some of the carbon dioxide in the blood. It has been shown by Kilmartin and Rossi Bernardi (1969) that CO2 combines rever- sibly at physiological pH and temperature with the terminal a-amino groups of the four peptide chains of haemoglobin to form a carbamate ion; RNH2 + CO2 ^ RNH. CO2- + HT Many years ago Christiansen et al (1914) demonstrated that deoxy¬ genated blood binds considerably more CO2 than does oxygenated blood. Thus although oxygen and carbon dioxide are held at quite different sites in the haemoglobin molecule, their respective reactions, although of a different type, nevertheless influence each other in a way which is of great physiological importance. This mutual interaction, incidentally, is another example of an allosteric effect in haemoglobin. THE GENETIC CONTROL OF HAEMOGLOBIN SYNTHESIS There is now good evidence from studies of a few critical families that the structures of the a-, ß-, y-. S- and presumably e-chains are controlled by