Iron is required for life. The
iron–sulfur clusters are pervasive and include
nitrogenase, the enzymes responsible for biological
nitrogen fixation. Iron-containing proteins participate in transport, storage and use of oxygen. The average adult human contains about 0.005% body weight of iron, or about four grams, of which three quarters is in hemoglobin—a level that remains constant despite only about one milligram of iron being absorbed each day, because the human body recycles its hemoglobin for the iron content. Microbial growth may be assisted by oxidation of iron(II) or by reduction of iron(III).
Biochemistry Iron acquisition poses a problem for aerobic organisms because ferric iron is poorly soluble near neutral pH. Thus, these organisms have developed means to absorb iron as complexes, sometimes taking up ferrous iron before oxidising it back to ferric iron. After uptake in human
cells, iron storage is precisely regulated. A major component of this regulation is the protein
transferrin, which binds iron ions absorbed from the
duodenum and carries it in the
blood to cells. Transferrin contains Fe3+ in the middle of a distorted octahedron, bonded to one nitrogen, three oxygens and a chelating
carbonate anion that traps the Fe3+ ion: it has such a high
stability constant that it is very effective at taking up Fe3+ ions even from the most stable complexes. At the bone marrow, transferrin is reduced from Fe3+ to Fe2+ and stored as
ferritin to be incorporated into hemoglobin. The most commonly known and studied
bioinorganic iron compounds (biological iron molecules) are the
heme proteins: examples are
hemoglobin,
myoglobin, and
cytochrome P450.
lipoxygenases, and
IRE-BP. Hemoglobin is an oxygen carrier that occurs in
red blood cells and contributes their color, transporting oxygen in the arteries from the lungs to the muscles where it is transferred to
myoglobin, which stores it until it is needed for the metabolic oxidation of
glucose, generating energy.
Carbon monoxide and
phosphorus trifluoride are poisonous to humans because they bind to hemoglobin similarly to oxygen, but with much more strength, so that oxygen can no longer be transported throughout the body. Hemoglobin bound to carbon monoxide is known as
carboxyhemoglobin. This effect also plays a minor role in the toxicity of
cyanide, but there the major effect is by far its interference with the proper functioning of the electron transport protein
cytochrome a. The cytochrome proteins also involve heme groups and are involved in the metabolic oxidation of glucose by oxygen. The sixth coordination site is then occupied by either another imidazole nitrogen or a
methionine sulfur, so that these proteins are largely inert to oxygen—with the exception of cytochrome a, which bonds directly to oxygen and thus is very easily poisoned by cyanide. Here, the electron transfer takes place as the iron remains in low spin but changes between the +2 and +3 oxidation states. Since the reduction potential of each step is slightly greater than the previous one, the energy is released step-by-step and can thus be stored in
adenosine triphosphate. Cytochrome a is slightly distinct, as it occurs at the mitochondrial membrane, binds directly to oxygen, and transports protons as well as electrons, as follows: :4 Cytc2+ + O2 + 8H → 4 Cytc3+ + 2 H2O + 4H Although the heme proteins are the most important class of iron-containing proteins, the
iron–sulfur proteins are also very important, being involved in electron transfer, which is possible since iron can exist stably in either the +2 or +3 oxidation states. These have one, two, four, or eight iron atoms that are each approximately tetrahedrally coordinated to four sulfur atoms; because of this tetrahedral coordination, they always have high-spin iron. The simplest of such compounds is
rubredoxin, which has only one iron atom coordinated to four sulfur atoms from
cysteine residues in the surrounding peptide chains. Another important class of iron–sulfur proteins is the
ferredoxins, which have multiple iron atoms. Transferrin does not belong to either of these classes. The ability of sea
mussels to maintain their grip on rocks in the ocean is facilitated by their use of
organometallic iron-based bonds in their protein-rich
cuticles. Based on synthetic replicas, the presence of iron in these structures increased
elastic modulus 770 times,
tensile strength 58 times, and
toughness 92 times. The amount of stress required to permanently damage them increased 76 times.
Nutrition Diet Iron is pervasive, but particularly rich sources of dietary iron include
red meat,
oysters,
beans,
poultry,
fish,
leaf vegetables,
watercress,
tofu, and
blackstrap molasses. Iron provided by
dietary supplements is often found as
iron(II) fumarate, although
iron(II) sulfate is cheaper and is absorbed equally well. is often added to foods such as breakfast cereals or enriched wheat flour. Iron is most available to the body when
chelated to amino acids and is also available for use as a common
iron supplement.
Glycine, the least expensive amino acid, is most often used to produce iron glycinate supplements.
Dietary recommendations The U.S. Institute of Medicine (IOM) updated Estimated Average Requirements (EARs) and Recommended Dietary Allowances (RDAs) for iron in 2001. The
European Food Safety Authority (EFSA) refers to the collective set of information as Dietary Reference Values, with Population Reference Intake (PRI) instead of RDA, and Average Requirement instead of EAR. AI and UL are defined the same as in the
United States. For women the PRI is 13 mg/day ages 1517 years, 16 mg/day for women ages 18 and up who are premenopausal and 11 mg/day postmenopausal. For pregnancy and lactation, 16 mg/day. For men the PRI is 11 mg/day ages 15 and older. For children ages 1 to 14, the PRI increases from 7 to 11 mg/day. The PRIs are higher than the U.S. RDAs, with the exception of pregnancy. The EFSA reviewed the same safety question did not establish a UL. Infants may require iron supplements if they are bottle-fed cow's milk. Frequent
blood donors are at risk of low iron levels and are often advised to supplement their iron intake. For U.S. food and dietary supplement labeling purposes, the amount in a serving is expressed as a percent of Daily Value (%DV). For iron labeling purposes, 100% of the Daily Value was 18 mg, and remained unchanged at 18 mg. A table of the old and new adult daily values is provided at
Reference Daily Intake.
Deficiency Iron deficiency is the most common
nutritional deficiency in the world. When loss of iron is not adequately compensated by adequate dietary iron intake, a state of
latent iron deficiency occurs, which over time leads to
iron-deficiency anemia if left untreated, which is characterised by an insufficient number of red blood cells and an insufficient amount of hemoglobin. Children,
pre-menopausal women (women of child-bearing age), and people with poor diet are most susceptible to the disease. Most cases of iron-deficiency anemia are mild, but if not treated can cause problems like fast or irregular heartbeat, complications during pregnancy, and delayed growth in infants and children. The brain is resistant to acute iron deficiency due to the slow transport of iron through the blood brain barrier. Acute fluctuations in iron status (marked by serum ferritin levels) do not reflect brain iron status, but prolonged nutritional iron deficiency is suspected to reduce brain iron concentrations over time. In the brain, iron plays a role in oxygen transport, myelin synthesis, mitochondrial respiration, and as a cofactor for neurotransmitter synthesis and metabolism. Animal models of nutritional iron deficiency report biomolecular changes resembling those seen in Parkinson's and Huntington's disease. However, age-related accumulation of iron in the brain has also been linked to the development of Parkinson's.
Excess Iron uptake is tightly regulated by the human body, which has no regulated physiological means of excreting iron. Only small amounts of iron are lost daily due to mucosal and skin epithelial cell sloughing, so control of iron levels is primarily accomplished by regulating uptake. Regulation of iron uptake is impaired in some people as a result of a
genetic defect that maps to the HLA-H gene region on
chromosome 6 and leads to abnormally low levels of
hepcidin, a key regulator of the entry of iron into the circulatory system in mammals. In these people, excessive iron intake can result in
iron overload disorders, known medically as
hemochromatosis. Overdoses of ingested iron can cause excessive levels of free iron in the blood. High blood levels of free ferrous iron react with
peroxides to produce highly reactive
free radicals that can damage
DNA,
proteins,
lipids, and other cellular components. Iron toxicity occurs when the cell contains free iron, which generally occurs when iron levels exceed the availability of
transferrin to bind the iron. Damage to the cells of the
gastrointestinal tract can also prevent them from regulating iron absorption, leading to further increases in blood levels. Iron typically damages cells in the
heart,
liver and elsewhere, causing adverse effects that include
coma,
metabolic acidosis,
shock,
liver failure,
coagulopathy, long-term organ damage, and even death.
In the human brain Iron is vital for function of the human brain. Iron is tightly regulated in the brain, limiting the impact of both iron deficiency and excess. If these systems are overwhelmed by nutritional deficiency, especially in pregnancy and infancy, there can be long-term health consequences but direct connections are difficult to establish because nutritional deficiency is usually linked to other health related problems. Excess iron is correlated with some neurodegenerative conditions but the cause is not known.
Cancer The role of iron in cancer defense can be described as a "double-edged sword" because of its pervasive presence in non-pathological processes. People having
chemotherapy may develop iron deficiency and
anemia, for which
intravenous iron therapy is used to restore iron levels. Iron overload, which may occur from high consumption of red meat, The acidophile bacteria
Acidithiobacillus ferrooxidans,
Leptospirillum ferrooxidans,
Sulfolobus spp.,
Acidianus brierleyi and
Sulfobacillus thermosulfidooxidans can oxidize ferrous iron enzymically. A sample of the fungus
Aspergillus niger was found growing from gold mining solution, and was found to contain cyano metal complexes such as gold, silver, copper iron and zinc. The fungus also plays a role in the solubilization of heavy metal sulfides.-->
Marine systems Iron plays an essential role in marine systems and can act as a limiting nutrient for planktonic activity. Because of this, too much of a decrease in iron may lead to a decrease in growth rates in phytoplanktonic organisms such as diatoms. Iron can also be oxidized by marine microbes under conditions that are high in iron and low in oxygen. Iron can enter marine systems through adjoining rivers and directly from the atmosphere. Once iron enters the ocean, it can be distributed throughout the water column through ocean mixing and through recycling on the cellular level. In the arctic, sea ice plays a major role in the store and distribution of iron in the ocean, depleting oceanic iron as it freezes in the winter and releasing it back into the water when thawing occurs in the summer. The iron cycle can fluctuate the forms of iron from aqueous to particle forms altering the availability of iron to primary producers. Increased light and warmth increases the amount of iron that is in forms that are usable by primary producers. ==See also==