Fetal hemoglobin protein structure

Fetal hemoglobin (also hemoglobin F or HbF) is the main oxygen transport protein in the fetus during the last seven months of development in the womb. Functionally, fetal hemoglobin differs most from adult hemoglobin in that it is able to bind oxygen with greater affinity than the adult form, giving the developing fetus better access to oxygen from the mother's bloodstream. The reactivation of fetal hemoglobin synthesis in adults has been used to treat sickle-cell disease since 1995. Image File history File links Hemoglobin_F.png Fetal hemoglobin (white background). ... Image File history File links Hemoglobin_F.png Fetal hemoglobin (white background). ... General Name, Symbol, Number oxygen, O, 8 Chemical series Nonmetals, chalcogens Group, Period, Block 16, 2, p Appearance colorless Atomic mass 15. ... A transport protein is a protein involved in facilitated diffusion. ... Fetus at eight weeks Foetus redirects here. ... Female internal reproductive anatomy The uterus or womb is the major female reproductive organ of most mammals, including humans. ... 3-dimensional structure of hemoglobin. ... Red blood cells (erythrocytes) are present in the blood and help carry oxygen to the rest of the cells in the body Blood is a circulating tissue composed of fluid plasma and cells (red blood cells, white blood cells, platelets). ... Sickle-shaped red blood cells Sickle cell disease is a general term for a group of genetic disorders caused by sickle hemoglobin (Hgb S). ... 1995 (MCMXCV) was a common year starting on Sunday of the Gregorian calendar. ...

Overview

The oxygen saturation curve for fetal hemoglobin (blue) appears left-shifted when compared to adult hemoglobin (red) since fetal hemoglobin has a greater affinity for oxygen.

Both mother and fetus share a common blood supply. In particular, the fetus's blood supply is delivered via the umbilical vein from the placenta, which is anchored to the wall of the mother's uterus. As blood courses through the mother, oxygen is delivered to capillary beds for gas exchange, and by the time blood reaches the capillaries of the placenta, its oxygen saturation has decreased considerably. In order to recover enough oxygen to sustain itself, the fetus must be able to bind oxygen with a greater affinity than the mother. Image File history File links HbA_vs_HbF_saturation_curve. ... Image File history File links HbA_vs_HbF_saturation_curve. ... 3-dimensional structure of hemoglobin Hemoglobin or haemoglobin is the iron-containing oxygen-transport metalloprotein in the red cells of the blood in mammals and other animals. ... Fetal circulation; the umbilical vein is the large, red vessel at the far left The umbilical vein is a blood vessel present during fetal development that carries oxygenated blood from the placenta to the growing fetus. ... The placenta is an ephemeral (temporary) organ present only in female placental mammals during gestation (pregnancy). ... The uterus or womb is the major female reproductive organ of most mammals, including humans. ... Capillaries are the smallest of a bodys blood vessels, measuring 5-10 μm. ... It has been suggested that this article or section be merged into Respiration (physiology). ...

Fetal hemoglobin's affinity for oxygen is substantially greater than that of adult hemoglobin. Notably, the P50 value for fetal hemoglobin (i.e., the partial pressure of oxygen at which the protein is 50% saturated; lower values indicate greater affinity) is roughly 19 mmHg, whereas adult hemoglobin has a value of approximately 26.8 mmHg. As a result, the so-called "oxygen saturation curve", which plots percent saturation vs. pO₂, is left-shifted for fetal hemoglobin in comparison to the same curve in adult hemoglobin. In biochemistry, P50 indicates the partial pressure of a gas required to achieve 50% enzyme saturation. ... In Chemistry, the partial pressure of a gas in a mixture or solution is what the pressure of that gas would be if all other components of the mixture or solution suddenly vanished without its temperature changing. ... One way of defining pressure is in terms of the height of a column of fluid that may be supported by that pressure; or the height of a column of fluid that exerts that pressure at its base. ...

This greater affininty for oxygen is explained by fetal hemoglobin's interaction with 2,3-bisphosphoglycerate (2,3-BPG). In adult red blood cells, this substance decreases the affinity of hemoglobin for oxygen. It is also present in fetal red blood cells, but does not interact with fetal hemoglobin, leaving its affinity for oxygen unchanged. Adult hemoglobin alone actually has a higher affinity for oxygen than its fetal equivalent, but the levels of 2,3-BPG reduce it. Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen from the lungs or gills to body tissues via the blood. ...

Distribution

After the first 10 to 12 weeks of development, the fetus' primary form of hemoglobin switches from embryonic hemoglobin to fetal hemoglobin. At birth, fetal hemoglobin comprises 50-95% of the child's hemoglobin. These levels decline after six months as adult hemoglobin synthesis is activated while fetal hemoglobin synthesis is deactivated. Soon after, adult hemoglobin (hemoglobin A in particular) takes over as the predominant form of hemoglobin in normal children. 3-dimensional structure of hemoglobin Hemoglobin or haemoglobin is the iron-containing oxygen-transport metalloprotein in the red cells of the blood in mammals and other animals. ...

Structure and genetics

Most types of normal hemoglobin, including hemoglobin A, hemoglobin A2, hemoglobin S, and hemoglobin F, are tetramers composed of four protein subunits and four heme prosthetic groups. Whereas adult hemoglobin is composed of two alpha and two beta subunits, fetal hemoglobin is composed of two alpha and two gamma subunits, commonly denoted as α₂γ₂. Because of its presence in fetal hemoglobin, the gamma subunit is commonly called the "fetal" hemoglobin subunit. 3-dimensional structure of hemoglobin Hemoglobin or haemoglobin is the iron-containing oxygen-transport metalloprotein in the red cells of the blood in mammals and other animals. ... Hemoglobin A2 is a normal variant of hemoglobin A that consists of two alpha and two delta chains and is found in small quantity in normal human blood. ... A tetramer is a protein with four subunits (tetrameric). ... In structural biology, a protein subunit or subunit protein is a single protein molecule that assembles (or coassembles) with other protein molecules to form a multimeric or oligomeric protein. ... Structure of Heme b A haem or heme is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. ... A prosthetic group is a nonprotein (non-amino acid) component of a conjugated protein. ...

In humans, each chromosome 11 contains two identical copies of the gene that encodes the gamma subunit. The gene that codes for the alpha subunit is located on chromosome 16 and is also present in duplicate. Chromosome 11 is one of the 23 pairs of chromosomes in humans. ... This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Chromosome 16 is one of the 23 pairs of chromosomes in humans. ...

Treatment of sickle cell anemia

Sickle-shaped red blood cells

When fetal hemoglobin production is switched off after birth, normal children begin producing hemoglobin B. But children with sickle-cell disease instead begin producing a long, slender form of hemoglobin called hemoglobin S. This variety of hemoglobin causes red blood cells to change their shape from round to sickle-shaped, which have a greater tendency to stack on top of one another and crowd blood vessels. These invariably lead to so-called painful vaso-occlusive episodes, which are a hallmark of the disease. Micrograph of sickled red blood cells, taken from the NIH (US government agency) site at http://www. ... Micrograph of sickled red blood cells, taken from the NIH (US government agency) site at http://www. ... Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen to body tissues via the blood. ... Sickle-shaped red blood cells Sickle cell disease is a general term for a group of genetic disorders caused by sickle hemoglobin (Hgb S). ... Human red blood cells Red blood cells are the most common type of blood cell and are the vertebrate bodys principal means of delivering oxygen from the lungs or gills to body tissues via the blood. ... Using a sickle A sickle is a curved, hand-held agricultural tool typically used for harvesting grain crops before the advent of modern harvesting machinery. ... The arterial system The blood vessels are part of the circulatory system and function to transport blood throughout the body. ... Sickle-shaped red blood cells Sickle cell anemia (American English), sickle cell anaemia (British English) or sickle cell disease is a genetic disease in which red blood cells may change shape under certain circumstances. ...

If fetal hemoglobin remains the predominant form of hemoglobin after birth, however, the number of painful episodes decreases in patients with sickle cell anemia. Hydroxyurea, used also as an anti-cancer drug, is a viable treatment for sickle cell anemia, as it promotes the production of fetal hemoglobin while inhibiting sickling due to hemoglobin S polymerization. Hydroxyurea chemical structure Hydroxyurea or hydroxycarbamide (rINN), (brand names include Hydrea®) is an antineoplastic drug used in hematological malignancies. ... When normal cells are damaged beyond repair, they are eliminated by apoptosis. ... Oral medication A medication is a licenced drug taken to cure or reduce symptoms of an illness or medical condition. ... Polymerization is a process of reacting monomer molecules together in a chemical reaction to forinear chains or a three-dimensional network of polymer chains [1]. There are many forms of polymerization and different systems exist to categorize them. ...

Combination therapy with hydroxyurea and recombinant erythropoietin—rather than treatment with hydroxyurea alone—has been shown to further elevate hemoglobin F levels and to promote the development of HbF-containing F-cells [1]. Erythropoietin Erythropoietin (or EPO) is a glycoprotein hormone that is a growth factor for erythrocyte (red blood cell) precursors in the bone marrow. ...

References

• Hemoglobin synthesis
• Hemoglobin structure and function
• Hemoglobin F fact sheet
• Fetal hemoglobin [doc]
• Hydroxyurea in sickle-cell disease
• Management of sickle-cell disease
• Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia (original 1995 study)

External links

• Hemoglobinopathies
• Transport across the placenta
• American Sickle Cell Anemia Association