hemoglobin A

Hemoglobin A is a tetrameric protein composed of two alpha-globin chains (encoded on chromosome 16) and two beta-globin chains (encoded on chromosome 11), each bound to a heme group containing iron in the ferrous (Fe2+) state that reversibly binds oxygen. HbA replaces fetal hemoglobin (HbF, α2γ2) as the dominant hemoglobin after birth, with the switch occurring around 6 months of age due to gamma-to-beta globin gene switching.

Clinically, HbA is central to understanding hemoglobinopathies. Sickle cell disease results from a point mutation (Glu6Val) in the beta-globin gene, producing HbS instead of HbA; heterozygotes (HbAS, sickle trait) have both HbA and HbS. Beta-thalassemia involves reduced or absent beta-globin chain synthesis, leading to decreased HbA and compensatory increases in HbA2 (α2δ2) and HbF. Hemoglobin electrophoresis or HPLC is used to quantify these different hemoglobin fractions for diagnosis.

HbA also has a variant, HbA1c (glycated hemoglobin), formed by non-enzymatic glycosylation of the beta chain's N-terminal valine in proportion to plasma glucose levels. HbA1c is a critical clinical marker for long-term glycemic control in diabetes mellitus, reflecting average blood glucose over the preceding 2-3 months (the lifespan of RBCs).

Understanding oxygen-hemoglobin dissociation curves is essential: HbA exhibits cooperative binding (sigmoidal curve), with allosteric modulators including 2,3-BPG, pH (Bohr effect), CO2, and temperature affecting oxygen affinity and delivery to tissues.