Iron has several vital functions in the body. It serves as a carrier of oxygen to the tissues from the lungs by red blood cell haemoglobin, as a transport medium for electrons within cells, and as an integrated part of important enzyme systems in various tissues. The physiology of iron has been extensively reviewed. Most of the iron in the body is present in the erythrocytes as haemoglobin, a molecule composed of four units, each containing one haeme group and one protein chain.

Although the iron content of the earth's crust is relatively high, in the human body is only 3-4 g of it. About two-thirds are in the blood.

Therapeutic use of iron dates back to thousands of years ago. Egyptians transcribed iron supplements for treatment of hair loss, while the Greeks recommending iron in addition to wine because it increases the potency of men.

Physiological role of iron

The red blood cells contain a protein called haemoglobin. Each haemoglobin binds four iron atoms. Iron in hemoglobin binds with oxygen as it passes through the blood vessels in the lungs and releases it in the tissues. After releasing from oxygen, iron binds carbon dioxide, a by-product of respiration, returning it to the lungs and releases into the environment. Erythrocytes and iron are updated every 120 days. Other iron containing protein is myoglobin, which carries oxygen to the muscles and is therefore essential for cellular activity of all tissues.

Many enzymes involved in metabolic processes also contain iron. This nutrient is essential for cell division, cell growth and the synthesis of DNA molecules. It is also important in protein metabolism.

Iron plays an important role in the transfer of oxygen by the cytochrome, molecule involved in energy production.

Thyroid hormones that regulate metabolic processes include iron in their structures. Iron is involved in the formation of connective tissues of several neurotransmitters in the brain.

The important role of iron is to strengthen the immune system.

Iron plays an important role in the transfer of oxygen by hemoglobin. At neutral pH the Fe(II) and Fe(III) iron are practically insoluble in water and therefore need special systems for the their transmission and insertion of to their functional compounds.

Distribution and function of iron compounds in humans

Metabolism

Iron in foods is commonly found in the ferric form (Fe³⁺) and is bound to organic molecules. In the stomach, where the pH is lower than 4, Fe(III) can dissociate and react with low molecular compounds such as fructose, ascorbic acid, citric acid, and amino acids and creates complexes that allow Fe³⁺ to remains soluble at a neutral pH as in the small intestine. Iron does not come out of the haeme in the stomach, but as such it enters the small intestine.

In healthy individuals only 5-30% iron is absorbed from the food. In childhood, the absorption is at the maximum, and decreases with age. In foods of animal origin iron is present in the form of organic haeme-iron, while in plant foods is in the form of inorganic non-haeme iron. These two types of iron are absorbed in different ways. It can be absorbed about 20-30% of haeme iron, as opposed to 2-5% of non-haeme iron. If we also consume Vitamin C with food, then the percentage of approved non-haeme iron increases to 50%. Vitamin A and beta-carotene may also increase the absorption of non-haeme iron.

If iron is in the ferrous form (Fe²⁺) it is absorbed much better than as Fe³⁺. Hydrochloric acid found in the stomach translates ferric iron in the ferrous form. Absorption of iron is a slow process that takes 2 to 4 hours. If the level of iron in the body is low, then absorption is better. In this case, the level of absorption can increase by 10 to 20%.

Various factors affecting the absorption of iron. For example, sugars (carbohydrates) and amino acids can increase absorption, while zinc, oxalates and green vegetables such as spinach, tannins in tea and coffee can reduce iron absorption. Phytates and unpolished grains may reduce absorption while in the presence of meat and Vitamin C can lead to the opposite effect. Milk proteins, albumin and soy protein can also reduce absorption.

Average daily loss of iron from the body is only 1 mg/day. Women also lose iron in menstrual period. So the only way to regulate the total amount of iron in the body is the absorption of iron. Approximately, we consume about 10-20 mg of iron each day, but the body absorbed less than 10%. So under normal circumstances, very small amount of iron is absorbed from food. Amounts excreted in urine are minimal. At the same time, a large part of the total iron in the body, continuously rearranges into different body parts using several metabolic circuits. The greatest need for iron is in childhood and adolescence. Children at this ages absorbed higher degree of iron from food than adults. Iron deficiency in childhood and adolescence, as well as in women with menstrual periods, can be attributed to a lack of iron in food. If the deficiency occurs in adults can usually be attributed to significant bleeding.

The number of red blood cells increases during pregnancy so the mother body uses larger amounts of iron, which must be constantly updated.

Iron absorption

The mucosa cells of the small intestine absorbed iron bonded to the haeme. Haeme is then broken down and the haeme release the iron. Non-haeme iron is absorbed in ferrous form – Fe²⁺. Fe²⁺ is absorbed in the duodenum cells, where is rapidly oxidized to Fe³⁺. Ferric ion – Fe³⁺ binds to a molecule of intracellular carriers. This carrier transfer Fe³⁺ to mitochondria and then Fe³⁺ is transported to apoferritin of apotransferrin.

Apoferritin (Mr = 500 kDa) is a molecule that is composed of 24 identical subunits, each with a molecular weight of about 18 kDa. One molecule of apoferritin can bind about 4300 atoms of iron to form ferritin, which is the primary iron storage protein.

Apotransferrin (Mr = 90 kDa) can bind two atoms of iron and in this form is called transferrin. Transferrin is a real carrier of iron and in plasma is one of the β-globulin.

Under normal conditions, when the adult daily absorbe about 1 mg of iron, intracellular iron carrier in the cell mucosa is almost completely saturated. It submit considerable amounts of iron to apoferritin to form ferritin and some of the iron it transfer to to mitochondria.

In case of iron deficiency the capacity of intracellular iron carrier increases and more iron will absorb available in food. Mitochondria will resume normal amount of iron, but the cell does not create ferritin, so that most of the iron will be delivered to plasma apotransfferin.

If there is an iron overload, the capacity of intracellular iron carrier decreases and saturates. The mucosa cell produces create substantial amounts of ferritin iron and less of it is transfered to apotransferrin. Hormone erythropoietin may accelerate the transfer of mucosal iron to transferrin in the plasma.

Release of ferritin iron which is in Fe³⁺ form in plasma involves its reduction to Fe²⁺. Then Fe²⁺ is reoxidized to Fe³⁺ that could be attached to transferrin.

Iron transport

Iron is transported to the storage place in the bone marrow and some quantity in the liver in the form of Fe³⁺ bound to transferrin, located in the plasma. Ferritin of reticuloendothelial system is suitable for iron storage. Ferritin, however, can be denatured by loosing of apoferritin subunits, and then is aggregated into micelles of hemosiderin. Hemosiderin has much more iron than ferritin and they are microscopic size particles. Hemosiderin is commonly found in cases of iron overload, when the synthesis of apoferritin and its iron saturation is at maximum. Iron from hemosiderin can be used for the synthesis of hemoglobin, but the mobilization of iron from hemosiderin is much slower than from ferritin.

The plasma does not contain ferritin, but there apoferritin and this indicate the amount of iron stored in reticuloendothelial system. In the process of ferritin emerging from apoferritin Fe²⁺ is binding on the inner surface of the apoferritin shell. Apoferitin now acts as ferrooxidase and it oxidize Fe²⁺ into Fe³⁺, which is then tightly binds to ferritin. To release from ferritin iron must be reduced to Fe²⁺.

An inherited disorder in the regulation of mucosa iron absorption leads to iron overload syndrome called haemochromatosis. In this disease, which affects several organ systems, absorbed daily 2 to 3 mg from the gastrointestinal tract, and not as it is normally about 1 mg. Thit mean that, for 20-30 years it leads that the body accumulate 20-30 g of iron, that is much more than the normal 3-4 g. The accumulated iron is stored in the deferred hemosiderin in the liver, pancreas, skin and joints, and this will lead to disease.

When the total amount of stored iron is high we have postponed haemosiderin then we can say that this is haemosiderosis. Haemosiderosis may occur due to increased intake of iron in food, and also because of increased degradation of red blood cells and increased absorption of iron as follows erythropoiesis. When haemosiderin deposits disrupt the normal function of cells and organs, then we are talking about haemochromatosis.

Food sources of iron

Meats, shellfish and legumes are rich sources of iron. Iron in foods is commonly found in the ferric form (Fe³⁺) and is tightly bonded to organic molecules.

Good sources of iron are also liver, meat, beans, nuts, dried fruit, poultry, fish, chokeberry. Cooking food in iron pots can increase the amount of iron in food up to 20%, but that form of iron is difficult to absorb. If food is cooked in such dishes longer time more iron is incorporated into the food. Substituting iron pan with aluminum, stainless steel and plastic, reduce the intake of iron in the body.

People who do not use red meat in their diet, which is the best source of iron in the body, have to increase the content of plant foods with dark-green leaves, beans and unpolished grains or iron supplements. Vegetarian diet would have to contain a greater amount of vitamin C which helps in absorption of iron.

Recommended daily allowance

Since the iron in red blood cells is recycled, to men and postmenopausal women are recommended small amounts of iron in the diet. Requirements for iron during pregnancy will grow due to the increased blood volume in pregnant women, as well as the needs of the foetus for iron.

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