Abstract
THE thalassaemia syndromes are associated with unbalanced synthesis of the globin chains of haemoglobin A (α2β2) (refs. 1–3). In cells of patients with α thalassaemia, there is a relative deficiency of α chain production; as a consequence, β chain tetramers known as haemoglobin H are formed and can be found in considerable quantities in the cells of these patients4. In the cells of patients with β thalassaemia, there is a marked decrease in β chain synthesis3,5,6, while α chain synthesis continues at a normal rate7. This leads to an accumulation of newly synthesized α chains which are not present in haemoglobins A or F, but can be characterized as α chain aggregates, ranging from monomers to tetramers, in the soluble fraction of the cell8,9. In spite of this biosynthetic evidence for the production of large amounts of α chain aggregates in the cells of patients with thalassaemia major (the homozygous condition) and minor (the heterozygous condition), intact α chains have not been reported in the cells of patients with thalassaemia minor, and are present in only small amounts in some cases of thalassaemia major10. One explanation of this is that the cells containing the greatest number of α chains uncombined with β or γ chains are preferentially destroyed in the bone marrow, or by the spleen or liver when they reach the peripheral blood11. On the other hand, the reticulocytes which survive in peripheral blood synthesize more α chains than β or γ chains3,5,6. This suggests the alternative possibility that α chains unassociated with β or γ chains might be selectively degraded by intracellular enzymatic proteolysis. Selective proteolytic digestion of normal globin chains has not been reported to date. Our results reported here, however, indicate that α chains synthesized in the cells of patients with β thalassaemia undergo significant intracellular proteolysis, while those present in non-thalassaemic cells do not.
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BANK, A., O'DONNELL, J. Intracellular Loss of Free α Chains in β Thalassaemia. Nature 222, 295–296 (1969). https://doi.org/10.1038/222295a0
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DOI: https://doi.org/10.1038/222295a0
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