Haemoglobin Synthesis in β‐Thalassaemia

Abstract

Summary. The incorporation of radioactive amino acids into the polypeptide chains of haemoglobin has been studied in reticulocyte preparations from five patients with β‐thalassaemia and four control patients. In both groups of patients an intracellular pool of free α‐chains has been found, but the pool is much larger in patients with β‐thalassaeniia major. The α‐chains exist in two forms: α‐dimers and α‐monomers, but the results suggest that they are released as dimers from the ribosomes and that the α‐chains for Hb‐A and Hb‐F synthesis are derived from the α‐dimer pool. The α‐dimers are also gradually converted to the monomers, and this may be the first stage in the denaturation of this protein. The results also show that the α‐dimer can exchange with the α‐chains of Hb‐A and that this exchange is more rapid in the presence of in vivo aged Hb‐A. In one patient with thalassaemia it was shown that there was no pool of unreleased β‐chains on the ribosomes. There is also no evidence for the release of incompleted β‐chains in our patients.

The Role of Alpha-Hemoglobin Stabilizing Protein in Redox Chemistry, Denaturation, and Hemoglobin Assembly

“…Given that a small pool of free a chains is known to exist in erythroblasts (8,20,40,64,77,93,97), Yu et al (119) hypothesized that the ill effects caused by Ahsp gene disruption might be mitigated by lowering a globin gene dosage. This would reduce or eliminate the pool of free a chains that are unescorted by AHSP, and consequently might lessen the severity of the Ahsp knockout phenotype (119).…”

Erythroid cell differentiation: murine erythroleukemia cell variant with unique pattern of induction by polar compounds.

“…Aliquots (25 ,l) of the incubation mixture were removed at intervals, 50 ,ug of bovine serum albumin was added, and the mixture was precipitated with 10% trichloroacetic acid, collected on Millipore filters, washed with 5% trichloroacetic acid, and counted by liquid scintillation with 0.2 ml of formic acid and 10 ml of Bray solution, for total protein synthesis. For globin synthesis cells were lysed and glohin chains were isolated by chromatography as described elsewhere (10,11 …”

“…Aliquots (25 ,l) of the incubation mixture were removed at intervals, 50 ,ug of bovine serum albumin was added, and the mixture was precipitated with 10% trichloroacetic acid, collected on Millipore filters, washed with 5% trichloroacetic acid, and counted by liquid scintillation with 0.2 ml of formic acid and 10 ml of Bray solution, for total protein synthesis. For globin synthesis cells were lysed and glohin chains were isolated by chromatography as described elsewhere (10,11 DR10c3 was otherwise similar in its karyotype to the parental line; both contain the same normal and rearranged (marker) chromosomes of mouse origin and show similar variation in the number of copies of specific chromosomes. The presence of identical marker chromosomes indicates that the two lines are closely related, as would be expected from their history.…”

Free α-Globin Pool in Human Bone Marrow

“…A very small pool of free a-chains has been demonstrated in peripheral blood of nonthalassemic patients by a sensitive method using gel filtration chromatography (6,7). In patients with homozygous P-thalassemia there is a marked decrease in synthesis of P-chains (3,4,8).…”

“…peripheral blood and bone marrow from these patients (6,7,9). In patients with heterozygous P-thalassemia there is decreased P-globin production in the peripheral blood reticulocytes (4,(10)(11)(12).…”