What regulates hemoglobin synthesis?
What regulates hemoglobin synthesis?
In heme deficiency, inhibition of protein synthesis correlates with the activation of heme-regulated eIF-2α kinase (HRI), which blocks the initiation of protein synthesis by phosphorylating eIF-2α. HRI is a hemoprotein with 2 distinct heme-binding domains.
How is globin chain production regulated in the body?
Normal α-globin synthesis is regulated by duplicate α-globin genes on chromosome 16. The genotype is usually represented as αα/αα and α-thalassaemia usually results from deletion of one or both α-genes. Occasionally point mutations in critical regions of the α-genes may cause non-deletional α-thalassaemia (αT).
How does heme regulate globin synthesis?
During the synthesis of hemoglobin, one molecule of heme is incorporated into each globin chain. When heme concentration is high, heme binds to the second heme-binding domain of HRI and keeps HRI in inactive state, thereby permitting globin protein synthesis and the formation of stable hemoglobin.
Where does the synthesis of globin starts?
Hemoglobin (Hb) is synthesized in a complex series of steps. The heme part is synthesized in a series of steps in the mitochondria and the cytosol of immature red blood cells, while the globin protein parts are synthesized by ribosomes in the cytosol.
What is globin synthesis?
Globin synthesis refers to the expression of the α-like and β-like globin genes in red blood cells. Mutations of these genes cause the ‘haemoglobinopathies’, the most common genetic disorders in humans.
What does globin do in hemoglobin?
The globins are a superfamily of heme-containing globular proteins, involved in binding and/or transporting oxygen. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members include myoglobin and hemoglobin.
What is HbA2 test?
The increase in hemoglobin A2 (HbA2) level is the most significant parameter in the identification of β-thalassemia carriers.
What is the function of globin in hemoglobin?
What will happen if there is no globin part in hemoglobin?
Alpha globin is made on chromosome 16. So, if any gene that tells chromosome 16 to produce alpha globin is missing or mutated, less alpha globin is made. This affects hemoglobin and decreases the ability of red blood cells to transport oxygen around the body.
What is HbA2 levels?
HbA2, composing of two α chains and two δ chains, is a minor component of the hemoglobin present in normal adult red blood cells, accounting for about 2.5% of the total hemoglobin in healthy individuals. However, HbA2 level is also elevated in some pregnant women.
Why is globin synthesis highly regulated in the body?
Globin synthesis is highly regulated so that there is a balanced production of globin and heme. This is critical because an excess of globin chains, protoporphyrin IX, or iron can accumulate and damage the cell, reducing its life span.
What is the history of gene regulation?
The field of gene regulation is also heavily indebted to scientists working on globins. β-globin was the first promoter to be extensively characterized in its constitutive elements (6) and the so-called LCR represented the first demonstration of the existence of distant regulatory elements controlling complex clusters of genes (7).
What happens when a globin gene is activated?
Consequently, when the programmed developmental time for the activation of a globin gene is reached, the transcription machinery will be positioned and engaged on its promoter even when the gene is defective and unable to produce any protein.
What is the function of aglobins?
Globins are ubiquitous heme-binding a-helical proteins whose function is principally thought to regulate oxygen homoeostasis [1, 2 ].
