Differences in affinity of beta and delta hemoglobin chains for alpha chains. A possible explanation for the variation in the percentages of hemoglobin A2 in thalassemia and other disorders.
Individual human alpha, beta and delta hemoglobin chain types were isolated in a native form so that the hemoglobin tetramers Hb A and Hb A2 could be reconstituted. In order to measure the relative affinity of beta and delta chains for alpha chains, an equimolar mixture of beta and delta chains was incubated with decreasing concentrations of alpha chains. When alpha chains were present in an amount equal to or greater than that of the mixture of beta and delta chains, the amount of Hb A2 was similar to that of Hb A. When alpha chains were in limiting concentrations, more Hb A than A2 was always formed with gradually decreasing amounts of Hb A2. The data as interpreted indicate that alpha chains have an affinity for beta chains at least 7.6-times greater than that for delta chains. These results also suggest that the differential affinity between beta and delta chains may be a major post-translational mechanism, which explains the increased level of Hb A2 in beta-thalassemia, and its reduced amounts in alpha-thalassemia and in acquired disorders with deficient alpha-chain synthesis.
D006441:Hemoglobin A / Q000378:metabolism*; D006443:Hemoglobin A2 / Q000378:metabolism*; D006454:Hemoglobins / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D046911:Macromolecular Substances; D013789:Thalassemia / Q000097:blood*
D006454:Hemoglobins; D046911:Macromolecular Substances; D006441:Hemoglobin A; D006443:Hemoglobin A2