HbA

Hemoglobin A (HbA) is the major adult form of hemoglobin and the primary oxygen transporter in healthy humans. In most adults, HbA comprises about 97% of circulating hemoglobin and is mainly HbA1, a tetramer made of two alpha and two beta globin chains (α2β2). A smaller fraction consists of HbA2 (α2δ2), about 2–3%, and fetal hemoglobin HbF (α2γ2) is normally less than 1% in adulthood.

Structure and function

HbA1 binds Oxygen in the lungs and releases it in tissues. The four globin chains coordinate with four heme groups containing iron, enabling reversible oxygen binding. The protein exhibits cooperativity and the Bohr effect, adjusting oxygen affinity in response to pH and carbon dioxide levels. The relative amounts of HbA1, HbA2, and HbF reflect developmental stages and physiological conditions.

Genetics and development

The alpha-globin genes HBA1 and HBA2 on chromosome 16 and the beta-globin gene HBB on chromosome 11 encode the major adult chains. The delta-globin gene HBD forms HbA2, and the gamma-globin genes HBG1/HBG2 form HbF. After birth, HbF declines while HbA1 rises to become the dominant form; HbA2 remains a stable minor component.

Clinical relevance

Variations in HbA or the presence of abnormal hemoglobins can lead to disease. Sickle cell disease arises from a Glu6Val mutation in the beta chain, producing HbS that can polymerize under low oxygen and deform red blood cells. Thalassemias involve reduced production of alpha or beta chains, altering HbA ratios and causing anemia. HbA measurements are also used in diagnostic testing and in monitoring therapy.

HbA1c

HbA1c is a related concept referring to the glycated fraction of HbA, used to monitor long-term glycemic control in diabetes. It reflects average blood glucose over roughly three months but can be affected by hemoglobin variants and red blood cell turnover.