Transferrins are glycoproteins found in vertebrates which bind and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encoded by the TF gene and produced as a 76 kDa glycoprotein.
Iron overload is the abnormal and increased accumulation of total iron in the body causing organ damage. Oxidative stress is the primary mediator of organ damage, as abnormally elevated intracellular iron levels increase free radical formation. Iron overload is often primary but may also be secondary to repeated blood transfusions. Iron deposition most commonly occurs in the liver, pancreas, skin, heart, and joints. People with iron overload, therefore, classically present with the triad of liver cirrhosis, secondary diabetes mellitus, and bronze skin. However, due to the earlier detection nowadays, symptoms are often limited to general chronic malaise, arthralgia, and hepatomegaly.
Anemia of chronic disease (ACD) or anemia of chronic inflammation is a form of anemia seen in chronic infection, chronic immune activation, and malignancy. These conditions all produce elevation of interleukin-6, which stimulates hepcidin production and release from the liver. Hepcidin production and release shuts down ferroportin, a protein that controls export of iron from the gut and from iron storing cells. As a consequence, circulating iron levels are reduced. Other mechanisms may also play a role, such as reduced erythropoiesis. It is also known as anemia of inflammation, or anemia of inflammatory response.
Human iron metabolism is the set of chemical reactions that maintain human homeostasis of iron at the systemic and cellular level. Iron is both necessary to the body and potentially toxic. Controlling iron levels in the body is a critically important part of many aspects of human health and disease. Hematologists have been especially interested in systemic iron metabolism, because iron is essential for red blood cells, where most of the human body's iron is contained. Understanding iron metabolism is also important for understanding diseases of iron overload, such as hereditary hemochromatosis, and iron deficiency, such as iron-deficiency anemia.
Hepcidin is a protein that in humans is encoded by the HAMP gene. Hepcidin is a key regulator of the entry of iron into the circulation in mammals.
Ferroportin-1, also known as solute carrier family 40 member 1 (SLC40A1) or iron-regulated transporter 1 (IREG1), is a protein that in humans is encoded by the SLC40A1 gene. Ferroportin is a transmembrane protein that transports iron from the inside of a cell to the outside of the cell. Ferroportin is the only known iron exporter.
Human homeostatic iron regulator protein, also known as the HFE protein, is a transmembrane protein that in humans is encoded by the HFE gene. The HFE gene is located on short arm of chromosome 6 at location 6p22.2
The Duke University School of Medicine, commonly known as Duke Med, is the medical school of Duke University. It was established in 1925 by James B. Duke.
Iron-binding proteins are carrier proteins and metalloproteins that are important in iron metabolism and the immune response. Iron is required for life.
Transferrin receptor (TfR) is a carrier protein for transferrin. It is needed for the import of iron into cells and is regulated in response to intracellular iron concentration. It imports iron by internalizing the transferrin-iron complex through receptor-mediated endocytosis. The existence of a receptor for transferrin iron uptake has been recognized since the late 1950s. Earlier two transferrin receptors in humans, transferrin receptor 1 and transferrin receptor 2 had been characterized and until recently cellular iron uptake was believed to occur chiefly via these two well documented transferrin receptors. Both these receptors are transmembrane glycoproteins. TfR1 is a high affinity ubiquitously expressed receptor while expression of TfR2 is restricted to certain cell types and is unaffected by intracellular iron concentrations. TfR2 binds to transferrin with a 25-30 fold lower affinity than TfR1. Although TfR1 mediated iron uptake is the major pathway for iron acquisition by most cells and especially developing erythrocytes, several studies have indicated that the uptake mechanism varies depending upon the cell type. It is also reported that Tf uptake exists independent of these TfRs although the mechanisms are not well characterized. The multifunctional glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase has been shown to utilize post translational modifications to exhibit higher order moonlighting behavior wherein it switches its function as a holo or apo transferrin receptor leading to either iron delivery or iron export respectively.
Iron is an important biological element. It is used in both the ubiquitous iron-sulfur proteins and in vertebrates it is used in hemoglobin which is essential for blood and oxygen transport.
Transferrin receptor protein 1 (TfR1), also known as Cluster of Differentiation 71 (CD71), is a protein that in humans is encoded by the TFRC gene. TfR1 is required for iron import from transferrin into cells by endocytosis.
Clement Alfred Finch was an American physician specializing in hematology whose research on iron metabolism in the bloodstream at the University of Washington led to significant advancements in accurately diagnosing and treating anemia during a time period in which little was known about this aspect of the body. Finch was distinctively noted for using himself as a test subject by taking blood and bone marrow from his own bones before conducting similar tests on patients. He graduated in 1941 from the University of Rochester Medical School and a year later was married to the first of three wives. He experienced a 60-year tenure at the University of Washington, and has published many scholarly articles pertaining to iron in the bloodstream and is the author of three books entitled: Iron Metabolism (1962), Red Cell Manual (1969) and Fulfilling the Dream: A History of the University of Washington School of Medicine 1946 to 1988 (1990). Finch was elected as a Fellow of the National Academy of Sciences in 1974, and elected as a Fellow of the American Academy of Arts and Sciences in 1976.
Leonard I. Zon, M.D., is the Grousbeck Professor of Pediatric Medicine at Harvard Medical School, Investigator at Howard Hughes Medical Institute, and Director of the Stem Cell Program, Children’s Hospital Boston.
JeffreyFlier is an American physician, endocrinologist; widely cited scientist; the Higginson Professor of Medicine and Physiology at Harvard Medical School; and a Distinguished Service Professor at the same institution. He was the 21st Dean of the Faculty of Medicine at Harvard University from 2007 to 2016.
Latent iron deficiency (LID), also called iron-deficient erythropoiesis, is a medical condition in which there is evidence of iron deficiency without anemia. It is important to assess this condition because individuals with latent iron deficiency may develop iron-deficiency anemia. Additionally, there is some evidence of a decrease in vitality and an increase in fatigue among individuals with LID.
Stuart Holland Orkin is an American physician, stem cell biologist and researcher in pediatric hematology-oncology. He is the David G. Nathan Distinguished Professor of Pediatrics at Harvard Medical School. Orkin's research has focused on the genetic basis of blood disorders. He is a member of the National Academy of Sciences and the Institute of Medicine, and an Investigator of the Howard Hughes Medical Institute.
Hemochromatosis type 4 is a hereditary iron overload disorder that affects ferroportin, an iron transport protein needed to export iron from cells into circulation. Although the disease is rare, it is found throughout the world and affects people from various ethnic groups. While the majority of individuals with type 4 hemochromatosis have a relatively mild form of the disease, some affected individuals have a more severe form. As the disease progresses, iron may accumulate in the tissues of affected individuals over time, potentially resulting in organ damage.
Iron preparation is the formulation for iron supplements indicated in prophylaxis and treatment of iron-deficiency anemia. Examples of iron preparation include ferrous sulfate, ferrous gluconate, and ferrous fumarate. It can be administered orally, and by intravenous injection, or intramuscular injection.
Tracey Ann Rouault is an American rheumatologist and physician-scientist who researches mammalian iron-sulfur proteins. Rouault is a senior investigator at the Eunice Kennedy Shriver National Institute of Child Health and Human Development and she heads the section on human iron metabolism.
