fetal hemoglobin , or fetal hemoglobin , (also hemoglobin F , HbF , or ? 2 2 ) is the main oxygen-carrying protein in the human fetus during the last seven months of development in the womb and persists in newborns up to about 6 months. Functionally, fetal hemoglobin is very different from adult hemoglobin because it is able to bind oxygen with a greater affinity than the adult form, giving the fetus a better access to oxygen from the mother's bloodstream.
In newborns, fetal hemoglobin is almost completely replaced by adult hemoglobin about 6 months after birth, except in some cases of thalassemia where there may be a delay in halting HbF production up to 3-5 years of age. In adults, fetal hemoglobin production can be pharmacologically reactivated, which is useful in the treatment of diseases such as sickle cell disease.
Video Fetal hemoglobin
Overview
Oxygenated blood is sent to the fetus through the umbilical vein of the placenta, which is anchored to the mother's uterine wall. Chorion acts as a barrier between maternal and fetal circulation so that there is no mixture of maternal and fetal blood. Blood in the mother's circulation is sent through the open arteriole to the intervillous chorionic plate chamber, where it baths chorionic villi carrying umbilical capillaries, allowing gas exchange to occur between the mother and fetal circulation. Deoxygenated mother's blood flows into the open intervillus venule and ends back into the mother's circulation. Because oxygenated and deoxygenated blood mixing, maternal blood in the intervillous space is lower in oxygen than in arterial blood. Thus, fetal hemoglobin should be able to bind oxygen with a greater affinity than adult hemoglobin to compensate for the relatively lower oxygen tension of the mother's blood supplying the chorion.
The affinity of fetal hemoglobin for oxygen is substantially greater than that of adult hemoglobin. In particular, the P50 value for fetal hemoglobin is lower than that of adult hemoglobin (ie, the oxygen partial pressure in which the protein is 50% saturated, the lower value indicates a greater affinity). P50 from fetal hemoglobin is about 19 mmHg, whereas adult hemoglobin is about 26.8 mmHg. As a result, the "oxygen saturation curve", which calculates the saturation percent vs. pO 2 , shifting to the left for fetal hemoglobin compared with adult hemoglobin.
This greater affinity for oxygen is explained by the lack of interaction of fetal hemoglobin with 2,3-biphosphoglycerate (2,3-BPG or 2,3-DPG). In adult red blood cells, this substance decreases the affinity of hemoglobin for oxygen. 2,3-BPG is also present in fetal red blood cells, but interacts less efficiently with fetal hemoglobin than in adult hemoglobin. This is due to a change in a single amino acid (residue 143) found in a 2,3-BPG 'binding bag: from histidine to serine, which causes an increase in oxygen affinity.
While histidine is positively charged and interacts well with the negative charge found on the 2.3-BPG surface, Serine has neutral side chains at physiological pH, and poorly interacted. This change produces less binding 2,3-BPG to fetal Hb, and as a result oxygen will bind it with a higher affinity than adult hemoglobin.
For mothers to deliver oxygen to the fetus, it is necessary for fetal hemoglobin to extract oxygen from oxygenated oxygen hemoglobin across the placenta. Higher oxygen affinity needed for fetal hemoglobin is achieved by protein subunits? (Gamma), is not it? (beta) subunit. Because? subunits have fewer positive charges than (adults)? subunit, 2,3-BPG less electrostatic bound to fetal hemoglobin compared with adult hemoglobin. This inherited affinity allows adult hemoglobin (maternal hemoglobin) to readily transfer oxygen to the fetal bloodstream.
Maps Fetal hemoglobin
Distribution
After the first 10-12 weeks of development, the primary form of fetal hemoglobin switches from embryonic hemoglobin to fetal hemoglobin. At birth, fetal hemoglobin comprises 50-95% of infant hemoglobin. This level decreases after six months when the synthesis of adult hemoglobin is activated while the synthesis of fetal hemoglobin is disabled. Soon after, adult hemoglobin (hemoglobin A in particular) takes over as the dominant form of hemoglobin in a normal child. However HbF has been traced even in adult blood (& lt; 1% of all hemoglobin).
Certain genetic abnormalities may cause a shift to the synthesis of adult hemoglobin to failure, resulting in a condition known as the hereditary persistence of fetal hemoglobin (HPFH).
Structure and genetics
Most normal hemoglobin types, including hemoglobin A, hemoglobin A2, and hemoglobin F, are tetramer consisting of four protein subunits and four heme prosthetic groups. Whereas adult hemoglobin consists of two? (alpha) and two? (beta) subunit, fetal hemoglobin consists of two? subunit and two ? (gamma) subunit, and is usually denoted as? 2 ? 2 . Because of its presence in fetal hemoglobin, is it? The subunit is usually called the "fetal" hemoglobin subunit.
In humans, gamma subunits are encoded on chromosome 11, as are beta subunits. There are two copies of the gamma subunit gene that are similar:? G which has glycine at position 136, and? A that has alanine. The gene encoding the alpha subunit lies on chromosome 16 and is also present in duplicate.
Clinical interests
Sickle cell disease treatment
When fetal hemoglobin production is switched off after birth, normal children begin to produce adult hemoglobin (HbA). Children with sickle cell disease begin to produce a form of hemoglobin defect called hemoglobin S that collects together and forms a filament that causes red blood cells to change from spherical to crescent shape. These damaged red blood cells have a greater tendency to accumulate on top of each other and block blood vessels. This always leads to so-called painful vaso-occlusive episodes , which are characteristic of the disease.
If fetal hemoglobin remains the dominant form of hemoglobin after birth, the number of painful episodes decreases in patients with sickle cell disease. Hydroxyurea promotes the production of fetal hemoglobin and thus can be used to treat sickle cell disease. The decrease in fetal hemoglobin in disease severity stems from its ability to inhibit the formation of hemoglobin aggregates in red blood cells that also contain hemoglobin S. Combination therapy with hydroxyurea and recombinant erythropoietin - rather than treatment with hydroxyurea alone - has been shown to further increase H hemoglobin levels and to promote development F cells containing HbF.
References
External links
- Hemoglobinopathies
- Carry the entire placenta
- American Ants Association of Cyclones
- SCDAA: Breaking the Cycles Cycle
- Synthesis of hemoglobin
- Structure and function of hemoglobin (archived February 3, 2002
- Fact sheets Hemoglobin F (archived October 29, 2009)
- Fetal hemoglobin (doc file; archived March 30, 2003)
- Hydroxyurea in sickle cell disease (archived on December 28, 2014 on [1])
- Chapter 26 Induction of Fetal Hemoglobin; Disease Management Sickle-Cell Edition 4 2002 (Publication NIH No. 02-2117)
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