Iron Metabolism
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 levelsin 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, wheremost of the human body'siron is contained. Understanding iron metabolism is also importantfor understanding diseasesof iron overload, such as hereditary hemochromatosis, and iron deficiency, such as iron-deficiency anemia. Iron is an essential bioelement for most forms of life, from bacteria to mammals. Its importance lies in its ability to mediate electrontransfer. In the ferrous state(Fe2+), iron acts as an electron donor, while in the ferricstate (Fe3+) it acts as an acceptor.Thus, iron playsa vital role in the catalysis of enzymatic reactions that involve electrontransfer (reduction and oxidation, redox). Proteins can contain iron as part of differentcofactors, such as iron–sulfur clusters(Fe-S) and heme groups, both of which are assembled in mitochondria.
Iron Absorption
Iron absorption occurs predominantly in the duodenum and upper jejunum . The mechanism of iron transport from the gut into the blood stream remains a mystery despite intensive investigation and a few tantalizing hits (see below). A feedback mechanism exists that enhances iron absorption in people who are iron deficient. In contrast, people with iron overload dampen iron absorption.
The physical state of iron entering the duodenum greatly influences its absorption however. At physiological pH, ferrous iron (Fe2+) is rapidly oxidized to the insoluble ferric (Fe3+) form.
Gastric acid lowers the pH in the proximal duodenum, enhancing the solubility and uptake of ferric iron. When gastricacid production is impaired (for instance by acid pump inhibitors such as the drug, Prilosec), iron absorption is reduced substantially.Heme is absorbed by machinery completely different to that of inorganic iron. The process is more efficient and is independent of duodenal pH . Consequently meats are excellent nutrient sources of iron. In fact, blockade of heme catabolism in the intestine by a heme oxygenase inhibitorcan produce iron deficiency . The paucity of meats in the diets of many of the people in the world adds to the burden of iron deficiency.
A number of dietary factors influence iron absorption. Ascorbate and citrate increase iron uptake in part by acting as weak chelators to help to solubilize the metal in the duodenum . Iron is readily transferred from these compounds into the mucosal lining cells. Conversely, iron absorption is inhibited by plant phytatesand tannins. Thesecompounds also chelateiron, but prevent its uptake by the absorption machinery . Phytates are prominent in wheat and some other cereals, while tannins are prevalent in (non-herbal) teas. Lead is a particularly pernicious element to iron metabolism . Lead is taken up by the iron absorption machinery, and secondarily blocks iron through competitive inhibition. Further, lead interferes with a number of important iron-dependent metabolic steps such as heme biosynthesis. This multifacted attack has particularly dire consequences in children, were lead not only produces anemia, but can impair cognitive development. Lead exists naturally at high levels in ground water and soil in some regions,and can clandestinely attack children's health.For this reason, most pediatricians in the U.S. routinely test for lead at an early age through a simple blood test.
Immaturity of the gastrointestinal tract can exacerbate iron deficiency in newborns. The gastrointestinal tract does not achieve competency for iron absorption for several weeks after birth. The problem is even more severe for premature infants, who tend to be anemic for a variety of reasons. A substantial portion of iron stores in newborns are transferred from the mother late in pregnancy. Prematurity shortcircuits this process. Parenteral iron replacement is possible, but not often used because of the often delicate health of premature infants. Transfusion becomes the default option in this circumstance.
Iron Storage
Iron is storedin liver, spleen & bone marrow in the form of ferritin.• In the mucosal cells, ferritin is the temporary storage form of iron.Ferritin contains about 23% iron.Ferritin in plasma level is elevated in iron over load.Ferritin level in blood is an index of body iron stores.Ferritin is an acutephase reactant protein,elevated in inflammatory diseases..Ferritin is foundalmost in all cells of the body.Iron is supplied in the diet and 10 % of ingested iron is absorbedin the small intestine and transported to plasma.Iron in plasma is bound to globulin called Transferrin enters bone marrow incorporate into hemoglobin.Ferritin in liver cells and macrophages is the reserve for hemoglobin and another hemoprotein.Ferritin concentration decreases before the is a drop in the hemoglobin, and changes in the RBCs morphology or serum iron concentration. Hemosiderin is another iron storage protein, which can hold about 35% of iron by weight. Hemosiderin accumulates when iron levels are increased.This hemosiderin is aggregated, partially deproteinized ferritin, is insoluble in the aqueous solution and is found in the liver cells, spleen, and bone marrow.Iron is supplied to the body in the diet. Where 10% of iron is absorbed in the small intestineand delivered to the blood.
(ferritin structure)
References
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