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Human iron metabolism

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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.

Importance of iron regulation

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Iron is an essential bioelement for most forms of life, from bacteria to mammals. Its importance lies in its ability to mediate electron transfer. In the ferrous state, iron acts as an electron donor, while in the ferric state it acts as an acceptor. Thus, iron plays a vital role in the catalysis of enzymatic reactions that involve electron transfer (reduction and oxidation, redox). Proteins can contain iron as part of different cofactors, such as iron-sulfur clusters (Fe-S) and heme groups, both of which are assembled in mitochondria. Cellular respiration edit Human cells require iron in order to obtain energy as ATP from a multi-step process known as cellular respiration, more specifically from oxidative phosphorylation at the mitochondrial cristae. Iron is present in the iron-sulfur clusters and heme groups of the electron transport chain proteins that generate a proton gradient that allows ATP synthase to synthesize ATP (chemiosmosis). Heme groups are part of hemoglobin, a protein

Body iron stores

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Most well-nourished people in industrialized countries have 4 to 5 grams of iron in their bodies (∼38 mg iron/kg body weight for women and ∼50 mg iron/kg body for men). Of this, about 2.5 g is contained in the hemoglobin needed to carry oxygen through the blood (around 0.5 mg of iron per mL of blood), and most of the rest (approximately 2 grams in adult men, and somewhat less in women of childbearing age) is contained in ferritin complexes that are present in all cells, but most common in bone marrow, liver, and spleen. The liver stores of ferritin are the primary physiologic source of reserve iron in the body. The reserves of iron in industrialized countries tend to be lower in children and women of child-bearing age than in men and in the elderly. Women who must use their stores to compensate for iron lost through menstruation, pregnancy or lactation have lower non-hemoglobin body stores, which may consist of 500 mg , or even less. Of the body's total iron content, about 400 mg

Mechanisms of iron regulation

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Human iron homeostasis is regulated at two different levels. Systemic iron levels are balanced by the controlled absorption of dietary iron by enterocytes, the cells that line the interior of the intestines, and the uncontrolled loss of iron from epithelial sloughing, sweat, injuries and blood loss. In addition, systemic iron is continuously recycled. Cellular iron levels are controlled differently by different cell types due to the expression of particular iron regulatory and transport proteins. Systemic iron regulation edit Dietary iron uptake edit The absorption of dietary iron is a variable and dynamic process. The amount of iron absorbed compared to the amount ingested is typically low, but may range from 5% to as much as 35% depending on circumstances and type of iron. The efficiency with which iron is absorbed varies depending on the source. Generally, the best-absorbed forms of iron come from animal products. Absorption of dietary iron in iron salt form (as in most supplements)

Pathology

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Iron deficiency edit Functional or actual iron deficiency can result from a variety of causes. These causes can be grouped into several categories: Increased demand for iron, which the diet cannot accommodate. Increased loss of iron (usually through loss of blood). Nutritional deficiency. This can result due to a lack of dietary iron or consumption of foods that inhibit iron absorption. Absorption inhibition has been observed caused by phytates in bran, calcium from supplements or dairy products, and tannins from tea, although in all three of these studies the effect was small and the authors of the studies cited regarding bran and tea note that the effect will probably only have a noticeable impact when most iron is obtained from vegetable sources. Acid-reducing medications: Acid-reducing medications reduce the absorption of dietary iron. These medications are commonly used for gastritis, reflux disease, and ulcers. Proton pump inhibitors (PPIs), H2 antihistamines, and antacids wil

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