Editing Iron (section)

===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.<ref name="lpi" /> In particular, bacteria have evolved very high-affinity [[wikt:sequester|sequestering]] agents called [[siderophore]]s.<ref>{{Cite journal |pmid=7592901 |doi=10.1074/jbc.270.45.26723 |date=1995 |last1=Neilands |first1=J.B. |title=Siderophores: structure and function of microbial iron transport compounds |volume=270 |issue=45 |pages=26723–26 |journal=The Journal of Biological Chemistry |doi-access=free}}</ref><ref>{{Cite journal |doi=10.1146/annurev.bi.50.070181.003435 |title=Microbial Iron Compounds |date=1981 |last1=Neilands |first1=J.B. |journal=Annual Review of Biochemistry |volume=50 |pages=715–31 |pmid=6455965|issue=1}}</ref><ref>{{Cite journal| doi=10.1023/A:1020218608266 |date=2002 |last1=Boukhalfa |first1=Hakim |last2=Crumbliss |first2=Alvin L. |journal=BioMetals |volume=15 |issue=4 |pages=325–39 |pmid=12405526 |title=Chemical aspects of siderophore mediated iron transport |s2cid=19697776}}</ref>

After uptake in human [[cell (biology)|cells]], iron storage is precisely regulated.<ref name="lpi" /><ref>{{Cite journal |title=Tumor necrosis factor-α-induced iron sequestration and oxidative stress in human endothelial cells |last11=Nakanishi |first11=T. |last10=Suzuki |first10=K. |first9=H. |last9=Eguchi |first8=M. |last8=Izumi |first7=Y. |last7=Hasuike |first6=K. |last6=Miyagawa |first5=R. |last5=Moriguchi |first4=K. |last4=Ito |first3=Y. |last3=Otaki |first2=T. |last2=Ookawara |first1=M. |last1=Nanami |pmid=16224057 |journal=Arteriosclerosis, Thrombosis, and Vascular Biology |date=2005 |volume=25 |issue=12 |pages=2495–501 |doi=10.1161/01.ATV.0000190610.63878.20 |doi-access=free}}</ref> A major component of this regulation is the protein [[transferrin]], which binds iron ions absorbed from the [[duodenum]] and carries it in the [[bloodstream|blood]] to cells.<ref name="lpi" /><ref>{{Cite journal|doi=10.1371/journal.pbio.0000079|title=How Mammals Acquire and Distribute Iron Needed for Oxygen-Based Metabolism|date=2003|last=Rouault|first = Tracey A.|author-link=Tracey Rouault|journal=PLOS Biology |volume=1 |issue=3 |pages=e9 |pmid=14691550|pmc=300689 |doi-access=free }}</ref> Transferrin contains Fe<sup>3+</sup> in the middle of a distorted octahedron, bonded to one nitrogen, three oxygens and a chelating [[carbonate]] anion that traps the Fe<sup>3+</sup> ion: it has such a high [[Stability constants of complexes|stability constant]] that it is very effective at taking up Fe<sup>3+</sup> ions even from the most stable complexes. At the bone marrow, transferrin is reduced from Fe<sup>3+</sup> to Fe<sup>2+</sup> and stored as [[ferritin]] to be incorporated into hemoglobin.{{sfn|Greenwood|Earnshaw|1997|pp=1098–104}} <!--Inorganic iron contributes to redox reactions in the [[iron–sulfur cluster]]s of many [[enzyme]]s, such as [[nitrogenase]] (involved in the synthesis of [[ammonia]] from [[nitrogen]] and [[hydrogen]]) and [[hydrogenase]]. Non-heme iron proteins include the [[enzymes]] [[methane monooxygenase]] (oxidizes [[methane]] to [[methanol]]), [[ribonucleotide reductase]] (reduces [[ribose]] to [[deoxyribose]]; [[DNA replication|DNA biosynthesis]]), [[hemerythrin]]s ([[oxygen]] transport and fixation in [[marine invertebrates]]) and purple [[acid phosphatase]] ([[hydrolysis]] of [[phosphate]] [[ester]]s).-->

The most commonly known and studied [[bioinorganic chemistry|bioinorganic]] iron compounds (biological iron molecules) are the [[heme proteins]]: examples are [[hemoglobin]], [[myoglobin]], and [[cytochrome P450]].<ref name="lpi" /> These compounds participate in transporting gases, building [[enzymes]], and transferring [[electron]]s.{{sfn|Greenwood|Earnshaw|1997|pp=1098–104}} [[Metalloproteins]] are a group of proteins with metal ion [[cofactor (biochemistry)|cofactors]]. Some examples of iron metalloproteins are [[ferritin]] and [[rubredoxin]].{{sfn|Greenwood|Earnshaw|1997|pp=1098–104}} Many enzymes vital to life contain iron, such as [[catalase]],<ref name="Boon_b">{{cite web |vauthors=Boon EM, Downs A, Marcey D |title=Proposed Mechanism of Catalase |work=Catalase: H<sub>2</sub>O<sub>2</sub>: H<sub>2</sub>O<sub>2</sub> Oxidoreductase: Catalase Structural Tutorial |url=https://biology.kenyon.edu/BMB/Chime/catalase/frames/cattx.htm#Proposed%20Mechanism%20of%20Catalase |access-date=2007-02-11}}</ref> [[lipoxygenases]],<ref>{{cite journal |vauthors=Boyington JC, Gaffney BJ, Amzel LM |title=The three-dimensional structure of an arachidonic acid 15-lipoxygenase |journal=Science |volume=260 |issue=5113 |pages=1482–86 |year=1993 |pmid=8502991 |doi=10.1126/science.8502991 |bibcode=1993Sci...260.1482B}}</ref> and [[IRE-BP]].<ref>{{cite journal |last1=Gray |first1=N.K. |last2=Hentze |first2=M.W. |title=Iron regulatory protein prevents binding of the 43S translation pre-initiation complex to ferritin and eALAS mRNAs |journal=EMBO J. |volume=13 |number=16 |pages=3882–91 |date=August 1994 |pmc=395301 |pmid=8070415 |doi=10.1002/j.1460-2075.1994.tb06699.x}}</ref>

Hemoglobin is an oxygen carrier that occurs in [[red blood cell]]s 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.<ref name="lpi" /> Here the hemoglobin binds to [[carbon dioxide]], produced when glucose is oxidized, which is transported through the veins by hemoglobin (predominantly as [[bicarbonate]] anions) back to the lungs where it is exhaled.{{sfn|Greenwood|Earnshaw|1997|pp=1098–104}} In hemoglobin, the iron is in one of four [[heme]] groups and has six possible coordination sites; four are occupied by nitrogen atoms in a [[porphyrin]] ring, the fifth by an [[imidazole]] nitrogen in a [[histidine]] residue of one of the protein chains attached to the heme group, and the sixth is reserved for the oxygen molecule it can reversibly bind to.{{sfn|Greenwood|Earnshaw|1997|pp=1098–104}} When hemoglobin is not attached to oxygen (and is then called deoxyhemoglobin), the Fe<sup>2+</sup> ion at the center of the [[heme]] group (in the hydrophobic protein interior) is in a [[Spin states (d electrons)#High-spin and low-spin systems|high-spin configuration]]. It is thus too large to fit inside the porphyrin ring, which bends instead into a dome with the Fe<sup>2+</sup> ion about 55 picometers above it. In this configuration, the sixth coordination site reserved for the oxygen is blocked by another histidine residue.{{sfn|Greenwood|Earnshaw|1997|pp=1098–104}}

When deoxyhemoglobin picks up an oxygen molecule, this histidine residue moves away and returns once the oxygen is securely attached to form a [[hydrogen bond]] with it. This results in the Fe<sup>2+</sup> ion switching to a low-spin configuration, resulting in a 20% decrease in ionic radius so that now it can fit into the porphyrin ring, which becomes planar.{{sfn|Greenwood|Earnshaw|1997|pp=1098–104}} Additionally, this hydrogen bonding results in the tilting of the oxygen molecule, resulting in a Fe–O–O bond angle of around 120° that avoids the formation of Fe–O–Fe or Fe–O<sub>2</sub>–Fe bridges that would lead to electron transfer, the oxidation of Fe<sup>2+</sup> to Fe<sup>3+</sup>, and the destruction of hemoglobin. This results in a movement of all the protein chains that leads to the other subunits of hemoglobin changing shape to a form with larger oxygen affinity. Thus, when deoxyhemoglobin takes up oxygen, its affinity for more oxygen increases, and vice versa.{{sfn|Greenwood|Earnshaw|1997|pp=1098–104}} Myoglobin, on the other hand, contains only one heme group and hence this cooperative effect cannot occur. Thus, while hemoglobin is almost saturated with oxygen in the high partial pressures of oxygen found in the lungs, its affinity for oxygen is much lower than that of myoglobin, which oxygenates even at low partial pressures of oxygen found in muscle tissue.{{sfn|Greenwood|Earnshaw|1997|pp=1098–104}} As described by the [[Bohr effect]] (named after [[Christian Bohr]], the father of [[Niels Bohr]]), the oxygen affinity of hemoglobin diminishes in the presence of carbon dioxide.{{sfn|Greenwood|Earnshaw|1997|pp=1098–104}}

[[File:Carboxyhemoglobin from 1AJ9.png|thumb|right|A heme unit of human [[carboxyhemoglobin]], showing the [[carbonyl ligand]] at the apical position, ''trans'' to the histidine residue<ref>{{cite journal | journal = Acta Crystallogr. D | title = Human Carboxyhemoglobin at 2.2 Å Resolution: Structure and Solvent Comparisons of R-State, R2-State and T-State Hemoglobins |author1=Gregory B. Vásquez |author2=Xinhua Ji |author3=Clara Fronticelli |author4=Gary L. Gilliland | doi = 10.1107/S0907444997012250 | pmid = 9761903 | volume = 54 | issue = 3 | pages = 355–66 | year = 1998| doi-access = free | bibcode = 1998AcCrD..54..355V }}</ref>]]
[[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]].{{sfn|Greenwood|Earnshaw|1997|pp=1098–104}} 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.{{sfn|Greenwood|Earnshaw|1997|pp=1098–104}} 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:{{sfn|Greenwood|Earnshaw|1997|pp=1098–104}}

:4 Cytc<sup>2+</sup> + O<sub>2</sub> + 8H{{su|p=+|b=inside}} → 4 Cytc<sup>3+</sup> + 2 H<sub>2</sub>O + 4H{{su|p=+|b=outside}}

Although the heme proteins are the most important class of iron-containing proteins, the [[iron–sulfur protein]]s 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 [[ferredoxin]]s, which have multiple iron atoms. Transferrin does not belong to either of these classes.{{sfn|Greenwood|Earnshaw|1997|pp=1098–104}}

The ability of sea [[mussel]]s to maintain their grip on rocks in the ocean is facilitated by their use of [[organometallic chemistry|organometallic]] iron-based bonds in their protein-rich [[cuticle]]s. 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.<ref>{{Cite journal| first = K| last = Sanderson|title = Mussels' iron grip inspires strong and stretchy polymer| journal = Chemical & Engineering News|page=8|volume = 95| issue = 44| publisher = American Chemical Society| date = 2017| url=https://cen.acs.org/articles/95/i44/Mussels-iron-grip-inspires-strong-stretchy-polymer.html|access-date=2 November 2017| doi=10.1021/cen-09544-notw3}}</ref>