Hemoglobin F

Hemoglobin F (HbF) is a type of hemoglobin that is predominantly found in the fetus and newborns. It is composed of two alpha (α) and two gamma (γ) globin chains, denoted as α2γ2. Hemoglobin F plays a crucial role in fetal development by facilitating the transfer of oxygen from the mother's bloodstream to the fetus.

Structure and Function

Hemoglobin F differs from adult hemoglobin (HbA) in its globin chain composition. While adult hemoglobin is composed of two alpha and two beta chains (α2β2), fetal hemoglobin contains gamma chains instead of beta chains. This difference in structure allows HbF to bind oxygen with a higher affinity than HbA, which is essential for efficient oxygen transfer across the placenta.

The high oxygen affinity of HbF is due to its reduced interaction with 2,3-bisphosphoglycerate (2,3-BPG), a molecule that decreases the oxygen affinity of hemoglobin. This property enables the fetus to extract oxygen from the maternal blood supply effectively.

Developmental Expression

The expression of hemoglobin F is highest during fetal development and begins to decline after birth. In the fetus, HbF constitutes approximately 70-90% of total hemoglobin. After birth, the production of gamma chains decreases, and beta chain production increases, leading to a gradual replacement of HbF with adult hemoglobin (HbA).

By the age of 6 months, the majority of hemoglobin in infants is adult hemoglobin, with HbF levels dropping to less than 1% in healthy adults. However, small amounts of HbF can persist into adulthood, particularly in certain conditions.

Clinical Significance

Hemoglobin F is of clinical interest in several hematological disorders. In conditions such as beta-thalassemia and sickle cell disease, increased levels of HbF can ameliorate symptoms by compensating for defective or deficient adult hemoglobin.

Therapeutic strategies that induce the production of HbF, such as the use of hydroxyurea, are employed to treat these disorders. Hydroxyurea increases HbF levels, which can reduce the severity of symptoms in sickle cell disease by inhibiting sickling of red blood cells.

Genetic Regulation

The production of hemoglobin F is regulated by the HBG1 and HBG2 genes, which encode the gamma globin chains. The switch from fetal to adult hemoglobin involves complex genetic regulation, including the silencing of gamma globin gene expression and activation of beta globin gene expression.

Research into the genetic mechanisms controlling this switch is ongoing, with the aim of developing new therapies for hemoglobinopathies by reactivating fetal hemoglobin production in adults.

Also see

• Hemoglobin
• Sickle cell disease
• Beta-thalassemia
• Oxygen transport
• Fetal development