Ересектердегі гемоглобин А және оның түрілерi

Normal human hemoglobin in adults

Hemoglobin A (HbA), also known as adult hemoglobin, hemoglobin A1 or α2β2, is the most common human hemoglobin tetramer, accounting for over 97% of the total red blood cell hemoglobin. Hemoglobin is an oxygen binding protein, found in erythrocytes, which transports oxygen from the lungs to the tissues. Hemoglobin A is the most common adult form of hemoglobin and exists as a tetramer containing two alpha subunits and two beta subunits (α2β2). Hemoglobin A2 (HbA2) is a less common adult form of hemoglobin and is composed of two alpha and two delta globin subunits. This hemoglobin makes up 1 3% of hemoglobin in adults.

Hemoglobin A (HbA) is the most common adult form of hemoglobin and exists as a tetramer containing two alpha subunits and two beta subunits (α2β2). In addition to oxygen, subunit assembly and quaternary structure are known to play important roles in Hb affinity. When hemoglobin binds to O2 (oxyhemoglobin), it will attach to the Iron II (Fe2+) of heme and it is this iron ion that can bind and unbind oxygen to transport oxygen throughout the body.

Heme synthesis involves a series of enzymatic steps that take place within the mitochondrion and cytosol of the cell. First, in the mitochondrion, the condensation of succinyl CoA and glycine by ALA synthase takes place to produce 5 aminolevulinic acid (ALA). ALA then moves to the cytosol and after a series of reactions creates coproporphyringen III. This molecule moves back into the mitochondrion where it reacts with protoporphyrin III oxidase to produce protoporphyrin IX. Iron is then enzymatically inserted into protoporphyrin via ferrochelatase to produce heme.

Globin synthesis takes place in the ribosomes which are located within the cytosol. Two globin chains that have heme groups combine to form hemoglobin. One of the chains is an alpha chain and the other is a non alpha chain. Non alpha chain nature in hemoglobin molecules varies due to different variables. Fetuses have a non alpha chain called gamma and after birth it is then called beta. The beta chain will pair with the alpha chain. It is the combining of two alpha and non alpha chains which create a hemoglobin molecule. Two alpha and two gamma chains form fetal hemoglobin or hemoglobin F (HbF). After the first five to six months after birth, the combining of two alpha chains and two beta chains form adult hemoglobin (HbA). The genes that encode for the alpha chains are located on chromosome 16, while the genes that encode for non alpha chains are located on chromosome 11. These hemoglobinopathies are often inherited as autosomal recessive traits.

Alpha thalassemia (α thalassemia) is defined by a lack of α globin chain production in hemoglobin, and those who carry a mutation impacting the α globin chain on only one chromosome are considered to have a “silent” α thalassemia whereas, if the mutation is on both then it is considered an α thalassemia trait. Like other hemoglobin related disorders (sickle cell and β thalassemia), it is hypothesized that α thalassemia is selected for within populations due to carriers being better protected against malaria falciparum. Single α globin gene carriers usually have no profound fatigue or anemia because they have a compensating increase in the number of microcytic red blood cells. This usually results in fatal hydrops fetalis and associated symptoms include intra uterine anemia, slowing of brain growth, oedema, deformities of the skeleton, and cardiovascular deformities that could lead to cardiac failure.

Sickle hemoglobin (HbS) is the most common variant of hemoglobin and arises due to an amino acid substitution in the beta globin subunit at the sixth residue from glutamic acid to valine. There are different forms of sickle cell disease. HB SS which is the most common and severe form of sickle cell. Hb SC is due to inheriting Hb S from one parent and Hb C (hemoglobin C) from the other parent. Hb S beta thalassemia is the least common and is experienced in patients who have inherited beta thalassemia hemoglobin from one parent and HbS from the other. In addition, there is sickle cell trait (HbAS) which is defined by having HbA and HbS. This makes the individual heterozygous for sickle cell. Of the world population, it is estimated that there are about 300 million individuals with the sickle cell trait and about 100 million of those are in sub Saharan Africa. There is also a higher prevalence of sickle cell trait in areas that malaria is commonly found, with the prevalence in some parts of Africa and Saudi Arabia being as high as 25% and 60%, respectively. Individuals who have HbAS have about 40%HbS, 56% HBA, and are usually asymptomatic unless there is a severe lack of oxygen to the body (hypoxia) which can lead to symptoms of sickle cell disease. Current treatments include blood transfusions which aid with increasing the number of normal red blood cells, bone marrow transplants to help the patients body produce healthy red blood cells, and medications to help alleviate the symptoms listed previously.