Iron

Metabolism



Iron in foods is commonly found in the ferric form (Fe(III) or 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 Fe(III) to remains soluble at a neutral pH as in the small intestine. Iron does not come out of the heme 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 heme-iron, while in plant foods is in the form of inorganic non-heme iron. These two types of iron are absorbed in different ways. It can be absorbed about 20-30% of heme iron, as opposed to 2-5% of non-heme iron. If we also consume Vitamin C with food, then the percentage of approved non-heme iron increases to 50%. Vitamin A and beta-carotene may also increase the absorption of non-heme iron.

If iron is in the ferrous form (Fe(II) or Fe2+) it is absorbed much better than as Fe(III). 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 absorbe 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 absorbe 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 absorbe iron bonded to the heme. Heme is then broken down and the heme release the iron. Non-heme iron is absorbed in ferrous form - Fe(II). Fe(II) is absorbed in the duodenum cells, where is rapidly oxidized to Fe(III). Ferric ion - Fe(III) binds to a molecule of intracellular carriers. This carrier transfer Fe(III) to mitochondria and then Fe(III) 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 Fe(III) form in plasma involves its reduction to Fe(II). Then Fe(II) is reoxidized to Fe(III) 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 Fe(III) 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 Fe(II) is binding on the inner surface of the apoferritin shell. Apoferitin now acts as ferrooxidase and it oxidize Fe(II) into Fe(III), which is then tightly binds to ferritin. To release from ferritin iron must be reduced to Fe(II).

An inherited disorder in the regulation of mucosa iron absorption leads to iron overload syndrome called hemochromatosis. 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.

Hemochromatosis
Different color of skin in hemochromatosis
(Image taken from consultantlive.com)

When the total amount of stored iron is high we have postponed hemosiderin then we can say that this is hemosiderosis. Hemosiderosis 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 hemosiderin deposits disrupt the normal function of cells and organs, then we are talking about hemochromatosis.