Imbalance in α and β Globin Synthesis Associated with a Hemoglobinopathy

Abstract

In contrast to findings in the thalassemia syndromes, studies of globin synthesis in subjects with structurally abnormal hemoglobins have generally revealed equal production of a and A polypeptide chains. However, in the present investigation of globin biosynthesis in vitro in blood and marrow from twoo subjects heterozygous for unstable hemoglobin Leiden, P66 or 7 Glu -* 0, a significant excess of a-chain production was revealed. A mother and daughter of northern European ancestry with mild compensated hemolytic anemia were found to have 25% hemoglobin Leiden. Increased hemolysis occurred after the ingestion of a sulfonamide and during infections. Normal levels of hemoglobin A2, 3.0 and 2.7%, and hemoglobin F, 0.8 and 0.6%, were found in the two subjects. Similar percentages of the minor hemoglobins were demonstrated in other family members without hemoglobin Leiden. After incubation of peripheral blood with [3H]-leucine, the #A/#Leiden synthesis ratio was 1.3, and the specific activity of pLelden was 1.3-2 times GAi. These results indicate preferential destruction of the unstable hemoglobin Leiden. However, in contrast to previous studies of other unstable hemoglobins, there was excess synthesis of a-chains. The total P/a synthesis ratio was 0.47-0.63 in peripheral blood and 0.82 in marrow. A pool of free a-chains was demonstrated by starch gel electrophoresis and DEAE column chromatography.

Erythropoiesis in Malaria Infections and Factors Modifying the Erythropoietic Response

“…Imbalance in α and β globin chains has been greatly discussed in cases of thalassemias [ 33 – 35 ]. Altered α / β globin gene expression ratio in such cases is an important indicator of ineffective erythropoiesis as well as disease severity [ 35 , 36 ].…”

Hemoglobin Indianapolis (beta 112[G14] arginine). An unstable beta-chain variant producing the phenotype of severe beta-thalassemia.

“…The ,8:a ratios in these hemoglobins range from 0.8 to 0.9. For two of these hemoglobins (Hbs Koln and Abraham Lincoln), experimental evidence suggested that this slight imbalance in globin chain synthesis is the result of early degradation of the unstable a-chain (41,46 (31).…”

It's not just a phase; ubiquitination in cytosolic protein quality control

“…Unlike prokaryotes which utilise operons to ensure the synthesis of related proteins in a coordinated manner, eukaryotes have a much more complicated cellular physiology which can lead to unassembled proteins [86,87]. The selective targeting of orphan proteins has been shown in the assembly of haemoglobin, a tetrameric complex composed of two α-globin subunits and two β-globin subunits, where mutations in haemoglobin result in dissociation of the complex and destruction of orphans to maintain proteostasis [88][89][90].…”