Hemoglobin A

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Hemoglobin A (HbA)

What it is
Hemoglobin A is the main form of hemoglobin in adults. It makes up about 97% of red blood cell hemoglobin. HbA is a tetramer, built from two alpha (α) chains and two beta (β) chains (α2β2). Each chain carries a heme group that can bind one molecule of oxygen, helping transport oxygen from the lungs to tissues throughout the body.

Structure and function
- Each of the four subunits has a heme group with iron that binds oxygen.
- When HbA binds oxygen, it becomes oxyhemoglobin and releases oxygen where it’s needed.
- All four subunits must be present for HbA to pick up and release oxygen normally.

How HbA is made
- Heme synthesis: Heme forms through steps that occur partly in mitochondria and partly in the cytosol. It starts with building a molecule called 5-aminolevulinic acid and ends with inserting iron into protoporphyrin IX to make heme.
- Globin synthesis: The protein parts of HbA are made in ribosomes in the cytosol. Two alpha chains and two beta chains come together to form HbA. The genes for these chains are located on two different chromosomes: alpha globin genes on chromosome 16 (HBA1 and HBA2) and beta globin genes on chromosome 11 (HBB and related genes). Fetal hemoglobin (HbF) uses gamma chains (α2γ2) instead of beta. HbA2 is another adult form (α2δ2) that makes up a small percentage.

Development and variants
- After birth, HbA becomes the predominant adult form as HbF levels fall.
- HbA2 and HbF remain present in smaller amounts.
- Other hemoglobins (like HbS, HbC, HbF) are variants that can affect health when inherited.

Clinical significance
Errors in HbA synthesis or in its globin or heme parts can lead to blood disorders:
- Alpha-thalassemia: reduced or absent production of alpha chains. In severe cases, Hb Bart’s (gamma tetramers) forms and doesn’t deliver oxygen well, which can be fatal before birth. Carriers are often asymptomatic.
- Beta-thalassemia: reduced or absent beta chain production. This can cause anemia and requires treatment, especially in severe forms. Carriers may have mild symptoms.
- Sickle cell disease: a common abnormal form (HbS) of the beta chain causes red blood cells to sickle under low oxygen. This can lead to pain episodes, anemia, and organ damage. Sickle cell trait (one HbS gene plus one normal HbA gene) usually causes few or no symptoms, but can cause problems under extreme conditions.

Simple takeaway
HbA is the most common adult hemoglobin, made from two alpha and two beta chains. It carries oxygen in the blood. Genetic changes can disrupt its production or produce variants like HbS, leading to conditions such as thalassemias or sickle cell disease, which vary in severity and needed treatment.