Excess α-Chain Synthesis relative to β-Chain Synthesis in Thalassaemia Major and Minor.

A Bank, PA Marks - Nature, 1966 - cabdirect.org
A Bank, PA Marks
Nature, 1966cabdirect.org
The now current explanation for the pathogenesis of β-thalassaemia is that the genetic
defect lies in the production of messenger-RNA for β-chain synthesis; fewer β-chains, and
hence an excess of α-chains result. The free excess of α-chains appears as insoluble
inclusions in red cells, which predisposes the cells to premature destruction. This is based
on the following experiments, which by their nature delineate the final stages of
haemoglobin production-that which occurs in circulating reticulocytes. The authors …
Abstract
The now current explanation for the pathogenesis of β-thalassaemia is that the genetic defect lies in the production of messenger-RNA for β-chain synthesis; fewer β-chains, and hence an excess of α-chains result. The free excess of α-chains appears as insoluble inclusions in red cells, which predisposes the cells to premature destruction. This is based on the following experiments, which by their nature delineate the final stages of haemoglobin production-that which occurs in circulating reticulocytes. The authors incubated red cells with radioactive leucine or valine, then separated the α-and β-chains chromatographically and measured the specific activity of the two globins. The reticulocytes of non-thalassaemic subjects synthesized both chains at the same rate (α/β ratio= 1). In thalassaemia minor the α/ratio was 2.3, and in thalassaemia major 5.2. But when purified haemoglobin was separated from the whole haemolysate of patients with thalassaemia major, its α/β ratio was found to be much lower than that in the whole haemolysate, showing that the latter contained α-chains that had not been built into complete haemoglobin molecules.[The older view, that α-chains could only be released in the presence of already formed β-chains, gave undue prominence to the hypoplastic aspects of Cooley's anaemia; the above view explains better its features of haemolysis, both in the marrow and the blood.] Alan B. Raper.
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