The switch from gamma to beta chain occurs through a transcriptional switch in erythroid precursor cells in the bone marrow. Approximately all HbF is replaced by HbA by 6 to 12 months of age unless hemoglobinopathy is present in the individual the average adult has less than 1% of HbF as a result. In the fetus, HbF is preceded by the embryonic hemoglobins, whose production in the yolk sac (weeks 3 through 8) decreases shortly after HbF is produced in the liver (weeks 6 through 30), followed by the spleen (9 through 28), and finally the bone marrow (28 through birth). The gamma-globin genes of fetal hemoglobin are products derived from duplications of beta-globin gene clusters. Mutations that resulted in changes to the primary structure of globin altered its properties and genetic regulatory regions. The evolution of hemoglobin follows gene mutations, such as gene duplication, gene conversion, and translocation of genes in ancient hemoproteins. The lower oxygen tension in the fetus is important for development, particularly angiogenesis. In the fetal systemic circulation, the low oxygen tension allows for proper unloading of oxygen, despite HbF's oxygen affinity. Fetal hematocrit (15g/dL) is higher than that in the mother (12g/dL), yielding a higher potential oxygen content per liter of blood. Another property of fetal circulation, allowing for oxygen transfer to the fetus, is fetal hematocrit. 2,3-DPG is essential for proper oxygen unloading in the postnatal circulation. A higher binding affinity to 2,3-DPG causes a right shift in HbA, favoring the unloading of oxygen. HbF also shows a decreased affinity for 2,3-bisphosphoglycerate (2,3-DPG), a metabolic intermediate produced in tissues with high energy use (low ATP, high acid production). This value indicates that HbF has a high affinity for oxygen, giving HbF the ability to bind oxygen more readily from the maternal circulation. The partial pressure at which HbF is half saturated with oxygen (P50) is 19 mm Hg, compared to 27 mm Hg for HbA. The HbF oxygen dissociation curve is left-shifted in comparison to HbA. Oxygen transfer from the maternal circulation to the fetal circulation is made possible by HbF having a high oxygen affinity but decreased affinity to 2,3-bisphosphoglycerate relative to HbA. Cellularįetal hemoglobin has a vital role in the transport of oxygen from maternal to fetal circulation. This difference introduces conformational changes to the protein that gives rise to several physiological differences in oxygen delivery that are important in fetal circulation. The gamma subunit differs from its adult counterpart in that it contains either an alanine or a glycine at position 136, both of which are neutral, nonpolar amino acids. The genes that express gamma chain proteins are present in the beta chain locus on chromosome 11. HbF contains two alpha and two gamma subunits, while the major form of adult hemoglobin, hemoglobin A (HbA), contains two alpha and two beta subunits. HbF is produced by erythroid precursor cells from 10 to 12 weeks of pregnancy through the first six months of postnatal life. Fetal hemoglobin (HbF) is the dominant form of hemoglobin present in the fetus during gestation.
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