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Hemoglobin is the oxygen-carrying protein that is found within all red blood cells (RBCs). It picks up oxygen where it is abundant (the lungs) and drops off oxygen where it is needed around the body. Hemoglobin is also the pigment that gives RBCs their red color. Heme groups and globins As its name suggests, hemoglobin is composed of "heme" groups (iron-containing rings) and "globins" (globular proteins). In fact, hemoglobin is composed of four globin proteins—two alpha chains and two beta chains—each with a heme group. The heme group contains one iron atom, and this can bind one molecule of oxygen. Because each molecule of hemoglobin contains four globins, it can carry up to four molecules of oxygen.
Hemoglobin transports oxygen In the lungs, a hemoglobin molecule is surrounded by a high concentration of oxygen, therefore, it binds oxygen. In active tissues, the oxygen concentration is lower, so hemoglobin releases its oxygen. This behavior is effective because the hemoglobin-oxygen binding is "co-operative", which means that the binding of one molecule of oxygen makes it easier for the binding of subsequent oxygen molecules. Likewise, the unbinding of oxygen makes it easier for other oxygen molecules to be released. Hence, the response of hemoglobin to the oxygen needs of active tissues is much quicker. Aside from the oxygen saturation of hemoglobin, other factors that influence how readily hemoglobin binds oxygen include plasma pH, plasma bicarbonate levels, and the pressure of oxygen in the air (high altitudes in particular). The molecule 2,3-disphosphoglycerate (2,3-DPG ) binds to hemoglobin and lowers its affinity for oxygen, thus promoting oxygen release. In individuals who have become acclimatized to living at high altitudes, the level of 2,3-DPG in the blood increases, allowing the delivery of more oxygen to tissues under low oxygen tension. Fetal hemoglobin Fetal hemoglobin differs from adult hemoglobin in that it contains two gamma chains instead of two beta chains. Fetal hemoglobin binds oxygen with a much greater affinity than adult hemoglobin; this is an advantage in the womb because it allows fetal blood to extract oxygen from maternal blood, despite its low concentration of oxygen. Normally, all fetal hemoglobin is replaced by adult hemoglobin by the time of birth. Breaking down hemoglobin Old or damaged RBCs are removed from the circulation by macrophages in the spleen and liver, and the hemoglobin they contain is broken down into heme and globin. The globin protein may be recycled, or broken down further to its constituent amino acids, which may be recycled or metabolized. The heme contains precious iron that is conserved and reused in the synthesis of new hemoglobin molecules. During its metabolism, heme is converted to bilirubin, a yellow pigment that can discolor the skin and sclera of the eye if it accumulates in the blood, a condition known as jaundice. Instead, the plasma protein albumin binds to bilirubin and carries it to the liver, where it is secreted in bile and also contributes to the color of feces. Jaundice is one of the complications of an incompatible blood transfusion. This occurs when the recipient's immune system attacks the donor RBCs as being foreign. The rate of RBC destruction and subsequent bilirubin production can exceed the capacity of the liver to metabolize the bilirubin produced. Hemoglobinopathies Hemoglobinopathies form a group of inherited diseases that are caused by mutations in the globin chains of hemoglobin. Sickle cell anemia is the most common of these and is attributable to a mutation that changes one of the amino acids in the hemoglobin beta chain, producing hemoglobin that is "fragile". When the oxygen concentration is low, RBCs tend to become distorted and "sickle" shaped. These deformed cells can block small blood vessels and damage the organs they are supplying. This can be very painful, and if not treated, a sickle cell crisis can be fatal. Another inherited anemia that particularly affects individuals of Mediterranean descent is thalassemia. A fault in the production of either alpha or beta globin chains causes a range of symptoms, depending on how many copies of the alpha and beta genes are affected. Some individuals may be carriers of the disease and have no symptoms, whereas if all copies of the genes are lost, the disease is fatal. The porphyrias are a group of inherited disorders in which the synthesis of heme is disrupted. Depending upon the stage at which the disruption occurs, there are a range of neurological and gastrointestinal side effects. King George III of England ("the madness of King George") was one of the most famous individuals who suffered from porphyria. Source: Blood Groups and Red Cell Antigens - published by National Library of Medicine, USA.
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