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Importance of iron regulation subsection</span> </button> <ul id="toc-Importance_of_iron_regulation-sublist" class="vector-toc-list"> <li id="toc-Cellular_respiration" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Cellular_respiration"> <div class="vector-toc-text"> <span class="vector-toc-numb">1.1</span> <span>Cellular respiration</span> </div> </a> <ul id="toc-Cellular_respiration-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Oxygen_transport" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Oxygen_transport"> <div class="vector-toc-text"> <span class="vector-toc-numb">1.2</span> <span>Oxygen transport</span> </div> </a> <ul id="toc-Oxygen_transport-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Toxicity" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Toxicity"> <div class="vector-toc-text"> <span class="vector-toc-numb">1.3</span> <span>Toxicity</span> </div> </a> <ul id="toc-Toxicity-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Bacterial_protection" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Bacterial_protection"> <div class="vector-toc-text"> <span class="vector-toc-numb">1.4</span> <span>Bacterial protection</span> </div> </a> <ul id="toc-Bacterial_protection-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Body_iron_stores" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Body_iron_stores"> <div class="vector-toc-text"> <span class="vector-toc-numb">2</span> <span>Body iron stores</span> </div> </a> <ul id="toc-Body_iron_stores-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Mechanisms_of_iron_regulation" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Mechanisms_of_iron_regulation"> <div class="vector-toc-text"> <span class="vector-toc-numb">3</span> <span>Mechanisms of iron regulation</span> </div> </a> <button aria-controls="toc-Mechanisms_of_iron_regulation-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle Mechanisms of iron regulation subsection</span> </button> <ul id="toc-Mechanisms_of_iron_regulation-sublist" class="vector-toc-list"> <li id="toc-Systemic_iron_regulation" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Systemic_iron_regulation"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.1</span> <span>Systemic iron regulation</span> </div> </a> <ul id="toc-Systemic_iron_regulation-sublist" class="vector-toc-list"> <li id="toc-Dietary_iron_uptake" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Dietary_iron_uptake"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.1.1</span> <span>Dietary iron uptake</span> </div> </a> <ul id="toc-Dietary_iron_uptake-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Iron_recycling_and_loss" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Iron_recycling_and_loss"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.1.2</span> <span>Iron recycling and loss</span> </div> </a> <ul id="toc-Iron_recycling_and_loss-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-Cellular_iron_regulation" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Cellular_iron_regulation"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.2</span> <span>Cellular iron regulation</span> </div> </a> <ul id="toc-Cellular_iron_regulation-sublist" class="vector-toc-list"> <li id="toc-Iron_import" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Iron_import"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.2.1</span> <span>Iron import</span> </div> </a> <ul id="toc-Iron_import-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Iron_import_in_some_cancer_cells" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Iron_import_in_some_cancer_cells"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.2.2</span> <span>Iron import in some cancer cells</span> </div> </a> <ul id="toc-Iron_import_in_some_cancer_cells-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-The_labile_iron_pool" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#The_labile_iron_pool"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.2.3</span> <span>The labile iron pool</span> </div> </a> <ul id="toc-The_labile_iron_pool-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-The_storage_iron_pool" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#The_storage_iron_pool"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.2.4</span> <span>The storage iron pool</span> </div> </a> <ul id="toc-The_storage_iron_pool-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Iron_export" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Iron_export"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.2.5</span> <span>Iron export</span> </div> </a> <ul id="toc-Iron_export-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Translational_control_of_cellular_iron" class="vector-toc-list-item vector-toc-level-3"> <a class="vector-toc-link" href="#Translational_control_of_cellular_iron"> <div class="vector-toc-text"> <span class="vector-toc-numb">3.2.6</span> <span>Translational control of cellular iron</span> </div> </a> <ul id="toc-Translational_control_of_cellular_iron-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> </ul> </li> <li id="toc-Pathology" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Pathology"> <div class="vector-toc-text"> <span class="vector-toc-numb">4</span> <span>Pathology</span> </div> </a> <button aria-controls="toc-Pathology-sublist" class="cdx-button cdx-button--weight-quiet cdx-button--icon-only vector-toc-toggle"> <span class="vector-icon mw-ui-icon-wikimedia-expand"></span> <span>Toggle Pathology subsection</span> </button> <ul id="toc-Pathology-sublist" class="vector-toc-list"> <li id="toc-Iron_deficiency" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Iron_deficiency"> <div class="vector-toc-text"> <span class="vector-toc-numb">4.1</span> <span>Iron deficiency</span> </div> </a> <ul id="toc-Iron_deficiency-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Iron_overload" class="vector-toc-list-item vector-toc-level-2"> <a class="vector-toc-link" href="#Iron_overload"> <div class="vector-toc-text"> <span class="vector-toc-numb">4.2</span> <span>Iron overload</span> </div> </a> <ul id="toc-Iron_overload-sublist" class="vector-toc-list"> </ul> </li> </ul> </li> <li id="toc-See_also" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#See_also"> <div class="vector-toc-text"> <span class="vector-toc-numb">5</span> <span>See also</span> </div> </a> <ul id="toc-See_also-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-References" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#References"> <div class="vector-toc-text"> <span class="vector-toc-numb">6</span> <span>References</span> </div> </a> <ul id="toc-References-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-Further_reading" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#Further_reading"> <div class="vector-toc-text"> <span class="vector-toc-numb">7</span> <span>Further reading</span> </div> </a> <ul id="toc-Further_reading-sublist" class="vector-toc-list"> </ul> </li> <li id="toc-External_links" class="vector-toc-list-item vector-toc-level-1 vector-toc-list-item-expanded"> <a class="vector-toc-link" href="#External_links"> <div class="vector-toc-text"> <span class="vector-toc-numb">8</span> <span>External links</span> </div> </a> <ul id="toc-External_links-sublist" class="vector-toc-list"> </ul> </li> </ul> </div> </div> </nav> </div> </div> <div class="mw-content-container"> <main id="content" class="mw-body"> <header class="mw-body-header vector-page-titlebar"> <nav aria-label="Contents" class="vector-toc-landmark"> <div id="vector-page-titlebar-toc" class="vector-dropdown vector-page-titlebar-toc vector-button-flush-left" > <input type="checkbox" id="vector-page-titlebar-toc-checkbox" role="button" aria-haspopup="true" data-event-name="ui.dropdown-vector-page-titlebar-toc" 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class="interlanguage-link-target"><span>العربية</span></a></li><li class="interlanguage-link interwiki-ca mw-list-item"><a href="https://ca.wikipedia.org/wiki/Metabolisme_hum%C3%A0_del_ferro" title="Metabolisme humà del ferro – Catalan" lang="ca" hreflang="ca" data-title="Metabolisme humà del ferro" data-language-autonym="Català" data-language-local-name="Catalan" class="interlanguage-link-target"><span>Català</span></a></li><li class="interlanguage-link interwiki-de mw-list-item"><a href="https://de.wikipedia.org/wiki/Eisen-Stoffwechsel" title="Eisen-Stoffwechsel – German" lang="de" hreflang="de" data-title="Eisen-Stoffwechsel" data-language-autonym="Deutsch" data-language-local-name="German" class="interlanguage-link-target"><span>Deutsch</span></a></li><li class="interlanguage-link interwiki-es mw-list-item"><a href="https://es.wikipedia.org/wiki/Metabolismo_humano_del_hierro" title="Metabolismo humano del hierro – Spanish" lang="es" hreflang="es" data-title="Metabolismo humano del hierro" data-language-autonym="Español" data-language-local-name="Spanish" class="interlanguage-link-target"><span>Español</span></a></li><li class="interlanguage-link interwiki-fr mw-list-item"><a href="https://fr.wikipedia.org/wiki/M%C3%A9tabolisme_du_fer" title="Métabolisme du fer – French" lang="fr" hreflang="fr" data-title="Métabolisme du fer" data-language-autonym="Français" data-language-local-name="French" class="interlanguage-link-target"><span>Français</span></a></li><li class="interlanguage-link interwiki-gl mw-list-item"><a href="https://gl.wikipedia.org/wiki/Metabolismo_do_ferro_humano" title="Metabolismo do ferro humano – Galician" lang="gl" hreflang="gl" data-title="Metabolismo do ferro humano" data-language-autonym="Galego" data-language-local-name="Galician" class="interlanguage-link-target"><span>Galego</span></a></li><li class="interlanguage-link interwiki-ko mw-list-item"><a href="https://ko.wikipedia.org/wiki/%EC%82%AC%EB%9E%8C%EC%9D%98_%EC%B2%A0_%EB%8C%80%EC%82%AC" title="사람의 철 대사 – Korean" lang="ko" hreflang="ko" data-title="사람의 철 대사" data-language-autonym="한국어" data-language-local-name="Korean" class="interlanguage-link-target"><span>한국어</span></a></li><li class="interlanguage-link interwiki-id mw-list-item"><a href="https://id.wikipedia.org/wiki/Zat_besi" title="Zat besi – Indonesian" lang="id" hreflang="id" data-title="Zat besi" data-language-autonym="Bahasa Indonesia" data-language-local-name="Indonesian" class="interlanguage-link-target"><span>Bahasa Indonesia</span></a></li><li class="interlanguage-link interwiki-it mw-list-item"><a href="https://it.wikipedia.org/wiki/Metabolismo_del_ferro" title="Metabolismo del ferro – Italian" lang="it" hreflang="it" data-title="Metabolismo del ferro" data-language-autonym="Italiano" data-language-local-name="Italian" class="interlanguage-link-target"><span>Italiano</span></a></li><li class="interlanguage-link interwiki-jv mw-list-item"><a href="https://jv.wikipedia.org/wiki/Dat_wesi" title="Dat wesi – Javanese" lang="jv" hreflang="jv" data-title="Dat wesi" data-language-autonym="Jawa" data-language-local-name="Javanese" class="interlanguage-link-target"><span>Jawa</span></a></li><li class="interlanguage-link interwiki-ms mw-list-item"><a href="https://ms.wikipedia.org/wiki/Zat_besi" title="Zat besi – Malay" lang="ms" hreflang="ms" data-title="Zat besi" data-language-autonym="Bahasa Melayu" data-language-local-name="Malay" class="interlanguage-link-target"><span>Bahasa Melayu</span></a></li><li class="interlanguage-link interwiki-nl mw-list-item"><a href="https://nl.wikipedia.org/wiki/IJzer_(voeding)" title="IJzer (voeding) – Dutch" lang="nl" hreflang="nl" data-title="IJzer (voeding)" data-language-autonym="Nederlands" data-language-local-name="Dutch" class="interlanguage-link-target"><span>Nederlands</span></a></li><li class="interlanguage-link interwiki-uz mw-list-item"><a href="https://uz.wikipedia.org/wiki/Odam_organizmida_temir_metabolizmi" title="Odam organizmida temir metabolizmi – Uzbek" lang="uz" hreflang="uz" data-title="Odam organizmida temir metabolizmi" data-language-autonym="Oʻzbekcha / ўзбекча" data-language-local-name="Uzbek" class="interlanguage-link-target"><span>Oʻzbekcha / ўзбекча</span></a></li><li class="interlanguage-link interwiki-pt mw-list-item"><a href="https://pt.wikipedia.org/wiki/Metabolismo_do_ferro" title="Metabolismo do ferro – Portuguese" lang="pt" hreflang="pt" data-title="Metabolismo do ferro" data-language-autonym="Português" data-language-local-name="Portuguese" class="interlanguage-link-target"><span>Português</span></a></li><li class="interlanguage-link interwiki-ro mw-list-item"><a href="https://ro.wikipedia.org/wiki/Metabolismul_fierului_%C3%AEn_organismul_uman" title="Metabolismul fierului în organismul uman – Romanian" lang="ro" hreflang="ro" data-title="Metabolismul fierului în organismul uman" 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searchaux" style="display:none">Iron metabolism in the body</div> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:Cellular_iron_homeostasis.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/9/97/Cellular_iron_homeostasis.png/400px-Cellular_iron_homeostasis.png" decoding="async" width="400" height="285" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/9/97/Cellular_iron_homeostasis.png/600px-Cellular_iron_homeostasis.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/9/97/Cellular_iron_homeostasis.png/800px-Cellular_iron_homeostasis.png 2x" data-file-width="884" data-file-height="630" /></a><figcaption>Diagram showing a generalized view of cellular iron homeostasis in humans. Iron import can occur via endocytosis of <a href="/wiki/Transferrin_receptor_1" title="Transferrin receptor 1">transferrin receptor 1</a> or via ferrous iron importers <a href="/wiki/DMT1" class="mw-redirect" title="DMT1">DMT1</a> and <a href="/w/index.php?title=ZIP14&action=edit&redlink=1" class="new" title="ZIP14 (page does not exist)">ZIP14</a>, which require the activity of iron reductases such as <a href="/wiki/STEAP2" title="STEAP2">STEAP2</a>, <a href="/w/index.php?title=Stromal_cell-derived_receptor_2&action=edit&redlink=1" class="new" title="Stromal cell-derived receptor 2 (page does not exist)">SDR-2</a> and <a href="/wiki/Dcytb" class="mw-redirect" title="Dcytb">Dcytb</a>. Intracellular iron can be stored in <a href="/wiki/Ferritin" title="Ferritin">ferritin</a> and used for protein biosynthesis, or to generate <a href="/wiki/Reactive_oxygen_species" title="Reactive oxygen species">reactive oxygen species</a> (ROS) and regulate transcription via <a href="/wiki/Iron-responsive_element-binding_protein" title="Iron-responsive element-binding protein">iron-responsive element-binding proteins</a> (IRP1/2). Export occurs through <a href="/wiki/Ferroportin" title="Ferroportin">ferroportin</a>, often aided by <a href="/wiki/Hephaestin" title="Hephaestin">hephaestin</a> (Hp) and/or <a href="/wiki/Ceruloplasmin" title="Ceruloplasmin">ceruloplasmin</a> (Cp), and repressed by <a href="/wiki/Hepcidin" title="Hepcidin">hepcidin</a>.</figcaption></figure> <p><b>Human iron metabolism</b> is the set of chemical reactions that maintain <a href="/wiki/Human_homeostasis" class="mw-redirect" title="Human homeostasis">human homeostasis</a> of <a href="/wiki/Iron" title="Iron">iron</a> 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. <a href="/wiki/Hematologist" class="mw-redirect" title="Hematologist">Hematologists</a> have been especially interested in systemic iron <a href="/wiki/Metabolism" title="Metabolism">metabolism</a>, because iron is essential for <a href="/wiki/Red_blood_cells" class="mw-redirect" title="Red blood cells">red blood cells</a>, where most of the human body's iron is contained. Understanding iron metabolism is also important for understanding diseases of <a href="/wiki/Iron_overload" title="Iron overload">iron overload</a>, such as <a href="/wiki/Hereditary_hemochromatosis" class="mw-redirect" title="Hereditary hemochromatosis">hereditary hemochromatosis</a>, and <a href="/wiki/Iron_deficiency" title="Iron deficiency">iron deficiency</a>, such as <a href="/wiki/Iron-deficiency_anemia" title="Iron-deficiency anemia">iron-deficiency anemia</a>. </p> <meta property="mw:PageProp/toc" /> <div class="mw-heading mw-heading2"><h2 id="Importance_of_iron_regulation">Importance of iron regulation</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=1" title="Edit section: Importance of iron regulation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:Heme_b.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/b/be/Heme_b.svg/180px-Heme_b.svg.png" decoding="async" width="180" height="199" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/b/be/Heme_b.svg/270px-Heme_b.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/b/be/Heme_b.svg/360px-Heme_b.svg.png 2x" data-file-width="620" data-file-height="685" /></a><figcaption>Structure of <a href="/wiki/Heme_b" class="mw-redirect" title="Heme b">Heme b</a>; "Fe" is the chemical symbol of iron, "II" indicates its oxidation state.</figcaption></figure> <p>Iron is an essential bioelement for most forms of life, from <a href="/wiki/Bacteria" title="Bacteria">bacteria</a> to <a href="/wiki/Mammals" class="mw-redirect" title="Mammals">mammals</a>. Its importance lies in its ability to mediate electron transfer. In the ferrous state (Fe<sup>2+</sup>), iron acts as an <a href="/wiki/Electron_donor" title="Electron donor">electron donor</a>, while in the ferric state (Fe<sup>3+</sup>) it acts as an <a href="/wiki/Electron_acceptor" title="Electron acceptor">acceptor</a>. Thus, iron plays a vital role in the <a href="/wiki/Catalysis" title="Catalysis">catalysis</a> of enzymatic reactions that involve electron transfer (reduction and oxidation, <a href="/wiki/Redox" title="Redox">redox</a>). Proteins can contain iron as part of different <a href="/wiki/Cofactor_(biochemistry)" title="Cofactor (biochemistry)">cofactors</a>, such as <a href="/wiki/Iron%E2%80%93sulfur_cluster" title="Iron–sulfur cluster">iron–sulfur clusters</a> (Fe-S) and <a href="/wiki/Heme" title="Heme">heme</a> groups, both of which are assembled in <a href="/wiki/Mitochondria" class="mw-redirect" title="Mitochondria">mitochondria</a>. </p> <div class="mw-heading mw-heading3"><h3 id="Cellular_respiration">Cellular respiration</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=2" title="Edit section: Cellular respiration"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1236090951">.mw-parser-output .hatnote{font-style:italic}.mw-parser-output div.hatnote{padding-left:1.6em;margin-bottom:0.5em}.mw-parser-output .hatnote i{font-style:normal}.mw-parser-output .hatnote+link+.hatnote{margin-top:-0.5em}@media print{body.ns-0 .mw-parser-output .hatnote{display:none!important}}</style><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Cellular_respiration" title="Cellular respiration">Cellular respiration</a></div> <p>Human cells require iron in order to obtain energy as <a href="/wiki/Adenosine_triphosphate" title="Adenosine triphosphate">ATP</a> from a multi-step process known as cellular respiration, more specifically from <a href="/wiki/Oxidative_phosphorylation" title="Oxidative phosphorylation">oxidative phosphorylation</a> at the mitochondrial <a href="/wiki/Cristae" class="mw-redirect" title="Cristae">cristae</a>. Iron is present in the iron–sulfur cluster and heme groups of the <a href="/wiki/Electron_transport_chain" title="Electron transport chain">electron transport chain</a> proteins that generate a <a href="/wiki/Proton_gradient" class="mw-redirect" title="Proton gradient">proton gradient</a> that allows <a href="/wiki/ATP_synthase" title="ATP synthase">ATP synthase</a> to synthesize ATP (<a href="/wiki/Chemiosmosis" title="Chemiosmosis">chemiosmosis</a>). </p><p>Heme groups are part of <a href="/wiki/Hemoglobin" title="Hemoglobin">hemoglobin</a>, a protein found in red blood cells that serves to transport oxygen from the <a href="/wiki/Lung" title="Lung">lungs</a> to other tissues. Heme groups are also present in <a href="/wiki/Myoglobin" title="Myoglobin">myoglobin</a> to store and diffuse oxygen in muscle cells. </p> <div class="mw-heading mw-heading3"><h3 id="Oxygen_transport">Oxygen transport</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=3" title="Edit section: Oxygen transport"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">See also: <a href="/wiki/Hemoglobin" title="Hemoglobin">Hemoglobin</a> and <a href="/wiki/Myoglobin" title="Myoglobin">myoglobin</a></div> <p>The human body needs iron for oxygen transport. Oxygen (O<sub>2</sub>) is required for the functioning and survival of nearly all cell types. Oxygen is transported from the lungs to the rest of the body bound to the <a href="/wiki/Heme" title="Heme">heme</a> group of <a href="/wiki/Hemoglobin" title="Hemoglobin">hemoglobin</a> in red blood cells. In muscles cells, iron binds oxygen to <a href="/wiki/Myoglobin" title="Myoglobin">myoglobin</a>, which regulates its release. </p> <div class="mw-heading mw-heading3"><h3 id="Toxicity">Toxicity</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=4" title="Edit section: Toxicity"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Iron is also potentially toxic. Its ability to donate and accept electrons means that it can catalyze the conversion of <a href="/wiki/Hydrogen_peroxide" title="Hydrogen peroxide">hydrogen peroxide</a> into <a href="/wiki/Free_radicals" class="mw-redirect" title="Free radicals">free radicals</a>. Free radicals can cause damage to a wide variety of cellular structures, and ultimately kill the cell.<sup id="cite_ref-pmid10787338_1-0" class="reference"><a href="#cite_note-pmid10787338-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> </p><p>Iron bound to proteins or <a href="/wiki/Cofactor_(biochemistry)" title="Cofactor (biochemistry)">cofactors</a> such as <a href="/wiki/Heme" title="Heme">heme</a> is safe. Also, there are virtually no truly free iron ions in the cell, since they readily form complexes with organic molecules. However, some of the intracellular iron is bound to low-affinity complexes, and is termed labile iron or "free" iron. Iron in such complexes can cause damage as described above.<sup id="cite_ref-Kakhlon_2002_2-0" class="reference"><a href="#cite_note-Kakhlon_2002-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> </p><p>To prevent that kind of damage, all life forms that use iron bind the iron atoms to <a href="/wiki/Proteins" class="mw-redirect" title="Proteins">proteins</a>. This binding allows cells to benefit from iron while also limiting its ability to do harm.<sup id="cite_ref-pmid10787338_1-1" class="reference"><a href="#cite_note-pmid10787338-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-Andrews_2000_3-0" class="reference"><a href="#cite_note-Andrews_2000-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> Typical intracellular labile iron concentrations in bacteria are 10-20 micromolar,<sup id="cite_ref-4" class="reference"><a href="#cite_note-4"><span class="cite-bracket">[</span>4<span class="cite-bracket">]</span></a></sup> though they can be 10-fold higher in anaerobic environment,<sup id="cite_ref-5" class="reference"><a href="#cite_note-5"><span class="cite-bracket">[</span>5<span class="cite-bracket">]</span></a></sup> where free radicals and <a href="/wiki/Reactive_oxygen_species" title="Reactive oxygen species">reactive oxygen species</a> are scarcer. In mammalian cells, intracellular labile iron concentrations are typically smaller than 1 micromolar, less than 5 percent of total cellular iron.<sup id="cite_ref-Kakhlon_2002_2-1" class="reference"><a href="#cite_note-Kakhlon_2002-2"><span class="cite-bracket">[</span>2<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Bacterial_protection">Bacterial protection</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=5" title="Edit section: Bacterial protection"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:E._coli_Bacteria_(7316101966).jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/3/3a/E._coli_Bacteria_%287316101966%29.jpg/220px-E._coli_Bacteria_%287316101966%29.jpg" decoding="async" width="220" height="185" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/3/3a/E._coli_Bacteria_%287316101966%29.jpg/330px-E._coli_Bacteria_%287316101966%29.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/3/3a/E._coli_Bacteria_%287316101966%29.jpg/440px-E._coli_Bacteria_%287316101966%29.jpg 2x" data-file-width="2100" data-file-height="1766" /></a><figcaption>Electron micrograph of <i><a href="/wiki/E._coli" class="mw-redirect" title="E. coli">E. coli</a></i>. Most bacteria that cause human disease require iron to live and to multiply.</figcaption></figure> <p>In response to a systemic bacterial infection, the immune system initiates a process known as "<a href="/w/index.php?title=Iron_withholding&action=edit&redlink=1" class="new" title="Iron withholding (page does not exist)">iron withholding</a>". If bacteria are to survive, then they must obtain iron from their environment. Disease-causing bacteria do this in many ways, including releasing iron-binding molecules called <a href="/wiki/Siderophores" class="mw-redirect" title="Siderophores">siderophores</a> and then reabsorbing them to recover iron, or scavenging iron from hemoglobin and <a href="/wiki/Transferrin" title="Transferrin">transferrin</a>. The harder the bacteria have to work to get iron, the greater a <a href="/wiki/Metabolic_price" class="mw-redirect" title="Metabolic price">metabolic price</a> they must pay. That means that iron-deprived bacteria reproduce more slowly. So, control of iron levels appears to be an important defense against many bacterial infections. Certain bacteria species have developed strategies to circumvent that defense, <a href="/wiki/Tuberculosis" title="Tuberculosis">TB</a> causing bacteria can reside within <a href="/wiki/Macrophages" class="mw-redirect" title="Macrophages">macrophages</a>, which present an iron rich environment and <i><a href="/wiki/Borrelia_burgdorferi" title="Borrelia burgdorferi">Borrelia burgdorferi</a></i> uses <a href="/wiki/Manganese" title="Manganese">manganese</a> in place of iron. People with increased amounts of iron, as, for example, in hemochromatosis, are more susceptible to some bacterial infections.<sup id="cite_ref-Ganz_2003_6-0" class="reference"><a href="#cite_note-Ganz_2003-6"><span class="cite-bracket">[</span>6<span class="cite-bracket">]</span></a></sup> </p><p>Although this mechanism is an elegant response to short-term bacterial infection, it can cause problems when it goes on so long that the body is deprived of needed iron for red cell production. Inflammatory <a href="/wiki/Cytokines" class="mw-redirect" title="Cytokines">cytokines</a> stimulate the liver to produce the iron metabolism regulator protein <a href="/wiki/Hepcidin" title="Hepcidin">hepcidin</a>, that reduces available iron. If hepcidin levels increase because of non-bacterial sources of inflammation, like viral infection, cancer, auto-immune diseases or other chronic diseases, then the <a href="/wiki/Anemia_of_chronic_disease" title="Anemia of chronic disease">anemia of chronic disease</a> may result. In this case, iron withholding actually impairs health by preventing the manufacture of enough hemoglobin-containing red blood cells.<sup id="cite_ref-Andrews_2000_3-1" class="reference"><a href="#cite_note-Andrews_2000-3"><span class="cite-bracket">[</span>3<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading2"><h2 id="Body_iron_stores">Body iron stores</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=6" title="Edit section: Body iron stores"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:Gray72-en.svg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/7/74/Gray72-en.svg/300px-Gray72-en.svg.png" decoding="async" width="300" height="219" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/7/74/Gray72-en.svg/450px-Gray72-en.svg.png 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/7/74/Gray72-en.svg/600px-Gray72-en.svg.png 2x" data-file-width="721" data-file-height="526" /></a><figcaption>Illustration of blood cell production in the <a href="/wiki/Bone_marrow" title="Bone marrow">bone marrow</a>. In <a href="/wiki/Iron_deficiency" title="Iron deficiency">iron deficiency</a>, the bone marrow produces fewer blood cells, and as the deficiency gets worse, the cells become smaller.</figcaption></figure> <p>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).<sup id="cite_ref-7" class="reference"><a href="#cite_note-7"><span class="cite-bracket">[</span>7<span class="cite-bracket">]</span></a></sup> Of this, about <span class="nowrap"><span data-sort-value="6997250000000000000♠"></span>2.5 g</span> is contained in the hemoglobin needed to carry oxygen through the blood (around 0.5 mg of iron per mL of blood),<sup id="cite_ref-8" class="reference"><a href="#cite_note-8"><span class="cite-bracket">[</span>8<span class="cite-bracket">]</span></a></sup> and most of the rest (approximately 2 grams in adult men, and somewhat less in women of childbearing age) is contained in <a href="/wiki/Ferritin" title="Ferritin">ferritin</a> complexes that are present in all cells, but most common in bone marrow, <a href="/wiki/Liver" title="Liver">liver</a>, and <a href="/wiki/Spleen" title="Spleen">spleen</a>. 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 <a href="/wiki/Menstruation" title="Menstruation">menstruation</a>, <a href="/wiki/Pregnancy" title="Pregnancy">pregnancy</a> or <a href="/wiki/Lactation" title="Lactation">lactation</a> have lower non-hemoglobin body stores, which may consist of <span class="nowrap"><span data-sort-value="6996500000000000000♠"></span>500 mg</span>, or even less. </p><p>Of the body's total iron content, about <span class="nowrap"><span data-sort-value="6996399999999999999♠"></span>400 mg</span> is devoted to cellular proteins that use iron for important cellular processes like storing oxygen (myoglobin) or performing energy-producing redox reactions (<a href="/wiki/Cytochrome" title="Cytochrome">cytochromes</a>). A relatively small amount (3–4 mg) circulates through the <a href="/wiki/Blood_plasma" title="Blood plasma">plasma</a>, bound to transferrin.<sup id="cite_ref-urlRegulation_of_iron_balance_9-0" class="reference"><a href="#cite_note-urlRegulation_of_iron_balance-9"><span class="cite-bracket">[</span>9<span class="cite-bracket">]</span></a></sup> Because of its toxicity, free soluble iron is kept in low concentration in the body. </p><p><a href="/wiki/Iron_deficiency" title="Iron deficiency">Iron deficiency</a> first affects the storage of iron in the body, and depletion of these stores is thought to be relatively asymptomatic, although some vague and <a href="/wiki/Non-specific_symptom" class="mw-redirect" title="Non-specific symptom">non-specific symptoms</a> have been associated with it. Since iron is primarily required for hemoglobin, <a href="/wiki/Iron_deficiency_anemia" class="mw-redirect" title="Iron deficiency anemia">iron deficiency anemia</a> is the primary clinical manifestation of iron deficiency. Iron-deficient people will suffer or die from organ damage well before their cells run out of the iron needed for intracellular processes like electron transport. </p><p><a href="/wiki/Macrophages" class="mw-redirect" title="Macrophages">Macrophages</a> of the <a href="/wiki/Reticuloendothelial_system" title="Reticuloendothelial system">reticuloendothelial system</a> store iron as part of the process of breaking down and processing hemoglobin from engulfed red blood cells. Iron is also stored as a pigment called <a href="/wiki/Hemosiderin" title="Hemosiderin">hemosiderin</a>, which is an ill-defined deposit of protein and iron, created by macrophages where excess iron is present, either locally or systemically, e.g., among people with iron overload due to frequent blood cell destruction and the necessary transfusions their condition calls for. If systemic iron overload is corrected, over time the hemosiderin is slowly resorbed by the macrophages. </p> <div class="mw-heading mw-heading2"><h2 id="Mechanisms_of_iron_regulation">Mechanisms of iron regulation</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=7" title="Edit section: Mechanisms of iron regulation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-halign-right" typeof="mw:File/Frame"><a href="/wiki/File:Redbloodcells.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/1/13/Redbloodcells.jpg" decoding="async" width="144" height="166" class="mw-file-element" data-file-width="144" data-file-height="166" /></a><figcaption>Humans use <span class="nowrap"><span data-sort-value="6995199999999999999♠"></span>20 mg</span> of <a href="/wiki/Iron" title="Iron">iron</a> each day for the production of new <a href="/wiki/Red_blood_cell" title="Red blood cell">red blood cells</a>, much of which is recycled from old red blood cells.</figcaption></figure> <p>Human iron homeostasis is regulated at two different levels. Systemic iron levels are balanced by the controlled absorption of dietary iron by <a href="/wiki/Enterocytes" class="mw-redirect" title="Enterocytes">enterocytes</a>, the cells that line the interior of the <a href="/wiki/Intestines" class="mw-redirect" title="Intestines">intestines</a>, 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. </p> <div class="mw-heading mw-heading3"><h3 id="Systemic_iron_regulation">Systemic iron regulation</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=8" title="Edit section: Systemic iron regulation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:TEST_Hephaestin_illustration.png" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/7/71/TEST_Hephaestin_illustration.png/300px-TEST_Hephaestin_illustration.png" decoding="async" width="300" height="226" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/7/71/TEST_Hephaestin_illustration.png/450px-TEST_Hephaestin_illustration.png 1.5x, //upload.wikimedia.org/wikipedia/commons/7/71/TEST_Hephaestin_illustration.png 2x" data-file-width="600" data-file-height="451" /></a><figcaption>Hephaestin is an enzyme that helps release iron from enterocytes. The regulation of hephaestin expression is one of the mechanisms that control iron absorption by the body.</figcaption></figure> <div class="mw-heading mw-heading4"><h4 id="Dietary_iron_uptake">Dietary iron uptake</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=9" title="Edit section: Dietary iron uptake"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>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) varies somewhat according to the body's need for iron, and is usually between 10% and 20% of iron intake. Absorption of iron from animal products, and some plant products, is in the form of heme iron, and is more efficient, allowing absorption of from 15% to 35% of intake. Heme iron in animals is from blood and heme-containing proteins in meat and mitochondria, whereas in plants, heme iron is present in mitochondria in all cells that use oxygen for respiration. </p><p>Like most mineral nutrients, the majority of the iron absorbed from digested food or supplements is absorbed in the <a href="/wiki/Duodenum" title="Duodenum">duodenum</a> by <a href="/wiki/Enterocyte" title="Enterocyte">enterocytes</a> of the duodenal lining. These cells have special molecules that allow them to move iron into the body. To be absorbed, dietary iron can be absorbed as part of a protein such as heme protein or iron must be in its ferrous Fe<sup>2+</sup> form. A ferric reductase enzyme on the enterocytes' <a href="/wiki/Brush_border" title="Brush border">brush border</a>, duodenal cytochrome B (<a href="/wiki/Dcytb" class="mw-redirect" title="Dcytb">Dcytb</a>), reduces ferric Fe<sup>3+</sup> to Fe<sup>2+</sup>.<sup id="cite_ref-pmid11230685_10-0" class="reference"><a href="#cite_note-pmid11230685-10"><span class="cite-bracket">[</span>10<span class="cite-bracket">]</span></a></sup> A protein called divalent metal transporter 1 (<a href="/wiki/DMT1" class="mw-redirect" title="DMT1">DMT1</a>), which can transport several <a href="/wiki/Divalent" class="mw-redirect" title="Divalent">divalent</a> metals across the plasma membrane, then transports iron across the enterocyte's <a href="/wiki/Cell_membrane" title="Cell membrane">cell membrane</a> into the cell. If the iron is bound to heme, it is instead transported across the apical membrane by <a href="/wiki/Haem_carrier_protein_1" title="Haem carrier protein 1">heme carrier protein 1</a> (HCP1).<sup id="cite_ref-11" class="reference"><a href="#cite_note-11"><span class="cite-bracket">[</span>11<span class="cite-bracket">]</span></a></sup> Heme is then <a href="/wiki/Catabolized" class="mw-redirect" title="Catabolized">catabolized</a> by microsomal <a href="/wiki/Heme_oxygenase" title="Heme oxygenase">heme oxygenase</a> into <a href="/wiki/Biliverdin" title="Biliverdin">biliverdin</a>, releasing Fe<sup>2+</sup>.<sup id="cite_ref-12" class="reference"><a href="#cite_note-12"><span class="cite-bracket">[</span>12<span class="cite-bracket">]</span></a></sup> </p><p>These intestinal lining cells can then either store the iron as <a href="/wiki/Ferritin" title="Ferritin">ferritin</a>, which is accomplished by Fe<sup>2+</sup> binding to apoferritin (in which case the iron will leave the body when the cell dies and is sloughed off into <a href="/wiki/Feces" title="Feces">feces</a>), or the cell can release it into the body via the only known iron exporter in mammals, <a href="/wiki/Ferroportin" title="Ferroportin">ferroportin</a>. <a href="/wiki/Hephaestin" title="Hephaestin">Hephaestin</a>, a <a href="/wiki/Ferroxidase" title="Ferroxidase">ferroxidase</a> that can oxidize Fe<sup>2+</sup> to Fe<sup>3+</sup> and is found mainly in the small intestine, helps ferroportin transfer iron across the basolateral end of the intestine cells. Upon release into the bloodstream, Fe<sup>3+</sup> binds transferrin and circulates to tissues. In contrast, ferroportin is post-translationally repressed by <a href="/wiki/Hepcidin" title="Hepcidin">hepcidin</a>, a 25-amino acid peptide hormone. The body regulates iron levels by regulating each of these steps. For instance, enterocytes synthesize more Dcytb, DMT1 and ferroportin in response to iron deficiency anemia.<sup id="cite_ref-Fleming_Bacon_2005_13-0" class="reference"><a href="#cite_note-Fleming_Bacon_2005-13"><span class="cite-bracket">[</span>13<span class="cite-bracket">]</span></a></sup> Iron absorption from diet is enhanced in the presence of vitamin C and diminished by excess calcium, zinc, or manganese.<sup id="cite_ref-14" class="reference"><a href="#cite_note-14"><span class="cite-bracket">[</span>14<span class="cite-bracket">]</span></a></sup> </p><p>The human body's rate of iron absorption appears to respond to a variety of interdependent factors, including total iron stores, the extent to which the bone marrow is producing new red blood cells, the concentration of hemoglobin in the blood, and the oxygen content of the blood. The body also absorbs less iron during times of <a href="/wiki/Inflammation" title="Inflammation">inflammation</a>, in order to deprive bacteria of iron. Recent discoveries demonstrate that hepcidin regulation of ferroportin is responsible for the syndrome of anemia of chronic disease. </p> <div class="mw-heading mw-heading4"><h4 id="Iron_recycling_and_loss">Iron recycling and loss</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=10" title="Edit section: Iron recycling and loss"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Most of the iron in the body is hoarded and recycled by the reticuloendothelial system, which breaks down aged red blood cells. In contrast to iron uptake and recycling, there is no physiologic regulatory mechanism for <a href="/wiki/Excretion" title="Excretion">excreting</a> iron. People lose a small but steady amount by gastrointestinal blood loss, sweating and by shedding cells of the skin and the <a href="/wiki/Mucosa" class="mw-redirect" title="Mucosa">mucosal</a> lining of the <a href="/wiki/Gastrointestinal_tract" title="Gastrointestinal tract">gastrointestinal tract</a>. The total amount of loss for healthy people in the developed world amounts to an estimated average of <span class="nowrap"><span data-sort-value="6994100000000000000♠"></span>1 mg</span> a day for men, and 1.5–2 mg a day for women with regular menstrual periods.<sup id="cite_ref-15" class="reference"><a href="#cite_note-15"><span class="cite-bracket">[</span>15<span class="cite-bracket">]</span></a></sup> People with gastrointestinal parasitic infections, more commonly found in developing countries, often lose more.<sup id="cite_ref-pmid10787338_1-2" class="reference"><a href="#cite_note-pmid10787338-1"><span class="cite-bracket">[</span>1<span class="cite-bracket">]</span></a></sup> Those who cannot regulate absorption well enough get disorders of iron overload. In these diseases, the toxicity of iron starts overwhelming the body's ability to bind and store it.<sup id="cite_ref-urlIron_overload_syndromes_other_than_hereditary_hemochromatosis_16-0" class="reference"><a href="#cite_note-urlIron_overload_syndromes_other_than_hereditary_hemochromatosis-16"><span class="cite-bracket">[</span>16<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading3"><h3 id="Cellular_iron_regulation">Cellular iron regulation</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=11" title="Edit section: Cellular iron regulation"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <div class="mw-heading mw-heading4"><h4 id="Iron_import">Iron import</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=12" title="Edit section: Iron import"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Most cell types take up iron primarily through <a href="/wiki/Receptor-mediated_endocytosis" title="Receptor-mediated endocytosis">receptor-mediated endocytosis</a> via <a href="/wiki/Transferrin_receptor_1" title="Transferrin receptor 1">transferrin receptor 1</a> (TFR1), <a href="/wiki/Transferrin_receptor_2" title="Transferrin receptor 2">transferrin receptor 2</a> (TFR2) and <a href="/wiki/GAPDH" class="mw-redirect" title="GAPDH">GAPDH</a>. TFR1 has a 30-fold higher affinity for transferrin-bound iron than TFR2 and thus is the main player in this process.<sup id="cite_ref-17" class="reference"><a href="#cite_note-17"><span class="cite-bracket">[</span>17<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-18" class="reference"><a href="#cite_note-18"><span class="cite-bracket">[</span>18<span class="cite-bracket">]</span></a></sup> The higher order multifunctional glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) also acts as a transferrin receptor.<sup id="cite_ref-19" class="reference"><a href="#cite_note-19"><span class="cite-bracket">[</span>19<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-20" class="reference"><a href="#cite_note-20"><span class="cite-bracket">[</span>20<span class="cite-bracket">]</span></a></sup> Transferrin-bound ferric iron is recognized by these transferrin receptors, triggering a conformational change that causes endocytosis. Iron then enters the cytoplasm from the endosome via importer DMT1 after being reduced to its ferrous state by a STEAP family reductase.<sup id="cite_ref-Tango_21-0" class="reference"><a href="#cite_note-Tango-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> </p><p>Alternatively, iron can enter the cell directly via plasma membrane divalent cation importers such as DMT1 and ZIP14 (Zrt-Irt-like protein 14).<sup id="cite_ref-Lane_22-0" class="reference"><a href="#cite_note-Lane-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup> Again, iron enters the cytoplasm in the ferrous state after being reduced in the extracellular space by a reductase such as STEAP2, STEAP3 (in red blood cells), Dcytb (in enterocytes) and SDR2.<sup id="cite_ref-Tango_21-1" class="reference"><a href="#cite_note-Tango-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Iron_import_in_some_cancer_cells">Iron import in some cancer cells</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=13" title="Edit section: Iron import in some cancer cells"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Iron can also enter cells via <a href="/wiki/CD44" title="CD44">CD44</a> in complexes bound to <a href="/wiki/Hyaluronic_acid" title="Hyaluronic acid">hyaluronic acid</a> during <a href="/wiki/Epithelial%E2%80%93mesenchymal_transition" title="Epithelial–mesenchymal transition">epithelial–mesenchymal transition</a> (EMT). In this process, <a href="/wiki/Epithelium" title="Epithelium">epithelial cells</a> transform into <a href="/wiki/Mesenchymal_cells" class="mw-redirect" title="Mesenchymal cells">mesenchymal cells</a> with detachment from the <a href="/wiki/Basement_membrane" title="Basement membrane">basement membrane</a>, to which they’re normally anchored, paving the way for the newly differentiated motile mesenchymal cells to begin migration away from the epithelial layer.<sup id="cite_ref-CD_23-0" class="reference"><a href="#cite_note-CD-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-EMT_24-0" class="reference"><a href="#cite_note-EMT-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> </p><p>While EMT plays a crucial role in physiological processes like <a href="/wiki/Implantation_(embryology)" title="Implantation (embryology)">implantation</a>, where it enables the <a href="/wiki/Embryo" title="Embryo">embryo</a> to invade the <a href="/wiki/Endometrium" title="Endometrium">endometrium</a> to facilitate <a href="/wiki/Placenta" title="Placenta">placental</a> attachment, its dysregulation can also fuel the <a href="/wiki/Malignant_tumor" class="mw-redirect" title="Malignant tumor">malignant</a> spread of <a href="/wiki/Tumors" class="mw-redirect" title="Tumors">tumors</a> empowering them to invade surrounding tissues and establish distant colonies (<a href="/wiki/Metastasis" title="Metastasis">metastasis</a>).<sup id="cite_ref-EMT_24-1" class="reference"><a href="#cite_note-EMT-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> </p><p>Malignant cells often exhibit a heightened demand for iron, fueling their transition towards a more invasive mesenchymal state. This iron is necessary for the expression of mesenchymal genes, like those encoding <a href="/wiki/Transforming_growth_factor_beta" title="Transforming growth factor beta">transforming growth factor beta</a> (TGF-β), crucial for EMT. Notably, iron’s unique ability to catalyze <a href="/wiki/Protein" title="Protein">protein</a> and <a href="/wiki/DNA" title="DNA">DNA</a> <a href="/wiki/Demethylation" title="Demethylation">demethylation</a> plays a vital role in this gene expression process.<sup id="cite_ref-CD_23-1" class="reference"><a href="#cite_note-CD-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup> </p><p>Conventional iron uptake pathways, such as those using the transferrin receptor 1 (TfR1), often prove insufficient to meet these elevated iron demands in cancer cells. As a result, various <a href="/wiki/Cytokines" class="mw-redirect" title="Cytokines">cytokines</a> and <a href="/wiki/Growth_factors" class="mw-redirect" title="Growth factors">growth factors</a> trigger the upregulation of CD44, a surface molecule capable of internalizing iron bound to the hyaluronan complex. This alternative pathway, relying on CD44-mediated endocytosis, becomes the dominant iron uptake mechanism compared to the traditional TfR1-dependent route.<sup id="cite_ref-CD_23-2" class="reference"><a href="#cite_note-CD-23"><span class="cite-bracket">[</span>23<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-EMT_24-2" class="reference"><a href="#cite_note-EMT-24"><span class="cite-bracket">[</span>24<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="The_labile_iron_pool">The labile iron pool</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=14" title="Edit section: The labile iron pool"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>In the cytoplasm, ferrous iron is found in a soluble, chelatable state which constitutes the labile iron pool (~0.001 mM).<sup id="cite_ref-Yehuda_25-0" class="reference"><a href="#cite_note-Yehuda-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> In this pool, iron is thought to be bound to low-mass compounds such as peptides, carboxylates and phosphates, although some might be in a free, hydrated form (<a href="/wiki/Metal_ions_in_aqueous_solution" title="Metal ions in aqueous solution">aqua ions</a>).<sup id="cite_ref-Yehuda_25-1" class="reference"><a href="#cite_note-Yehuda-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> Alternatively, iron ions might be bound to specialized proteins known as <a href="/wiki/Metallochaperones" title="Metallochaperones">metallochaperones</a>.<sup id="cite_ref-26" class="reference"><a href="#cite_note-26"><span class="cite-bracket">[</span>26<span class="cite-bracket">]</span></a></sup> Specifically, poly-r(C)-binding proteins <a href="/wiki/PCBP1" title="PCBP1">PCBP1</a> and <a href="/wiki/PCBP2" title="PCBP2">PCBP2</a> appear to mediate transfer of free iron to ferritin (for storage) and <a href="/wiki/Non-heme_iron_enzyme" class="mw-redirect" title="Non-heme iron enzyme">non-heme iron enzymes</a> (for use in catalysis).<sup id="cite_ref-Lane_22-1" class="reference"><a href="#cite_note-Lane-22"><span class="cite-bracket">[</span>22<span class="cite-bracket">]</span></a></sup><sup id="cite_ref-27" class="reference"><a href="#cite_note-27"><span class="cite-bracket">[</span>27<span class="cite-bracket">]</span></a></sup> The labile iron pool is potentially toxic due to iron's ability to generate reactive oxygen species. Iron from this pool can be taken up by mitochondria via <a href="/wiki/Mitoferrin-1" title="Mitoferrin-1">mitoferrin</a> to synthesize Fe-S clusters and heme groups.<sup id="cite_ref-Tango_21-2" class="reference"><a href="#cite_note-Tango-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="The_storage_iron_pool">The storage iron pool</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=15" title="Edit section: The storage iron pool"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Iron can be stored in ferritin as ferric iron due to the <a href="/wiki/Ferroxidase" title="Ferroxidase">ferroxidase</a> activity of the ferritin heavy chain.<sup id="cite_ref-28" class="reference"><a href="#cite_note-28"><span class="cite-bracket">[</span>28<span class="cite-bracket">]</span></a></sup> Dysfunctional ferritin may accumulate as <a href="/wiki/Hemosiderin" title="Hemosiderin">hemosiderin</a>, which can be problematic in cases of iron overload.<sup id="cite_ref-29" class="reference"><a href="#cite_note-29"><span class="cite-bracket">[</span>29<span class="cite-bracket">]</span></a></sup> The ferritin storage iron pool is much larger than the labile iron pool, ranging in concentration from 0.7 mM to 3.6 mM.<sup id="cite_ref-Yehuda_25-2" class="reference"><a href="#cite_note-Yehuda-25"><span class="cite-bracket">[</span>25<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Iron_export">Iron export</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=16" title="Edit section: Iron export"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Iron export occurs in a variety of cell types, including <a href="/wiki/Neuron" title="Neuron">neurons</a>, red blood cells, macrophages and enterocytes. The latter two are especially important since systemic iron levels depend upon them. There is only one known iron exporter, <a href="/wiki/Ferroportin" title="Ferroportin">ferroportin</a>.<sup id="cite_ref-30" class="reference"><a href="#cite_note-30"><span class="cite-bracket">[</span>30<span class="cite-bracket">]</span></a></sup> It transports ferrous iron out of the cell, generally aided by <a href="/wiki/Ceruloplasmin" title="Ceruloplasmin">ceruloplasmin</a> and/or <a href="/wiki/Hephaestin" title="Hephaestin">hephaestin</a> (mostly in enterocytes), which oxidize iron to its ferric state so it can bind ferritin in the extracellular medium.<sup id="cite_ref-Tango_21-3" class="reference"><a href="#cite_note-Tango-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Hepcidin" title="Hepcidin">Hepcidin</a> causes the internalization of ferroportin, decreasing iron export. Besides, hepcidin seems to downregulate both TFR1 and DMT1 through an unknown mechanism.<sup id="cite_ref-31" class="reference"><a href="#cite_note-31"><span class="cite-bracket">[</span>31<span class="cite-bracket">]</span></a></sup> Another player assisting ferroportin in effecting cellular iron export is GAPDH.<sup id="cite_ref-32" class="reference"><a href="#cite_note-32"><span class="cite-bracket">[</span>32<span class="cite-bracket">]</span></a></sup> A specific post translationally modified isoform of GAPDH is recruited to the surface of iron loaded cells where it recruits apo-transferrin in close proximity to ferroportin so as to rapidly chelate the iron extruded.<sup id="cite_ref-33" class="reference"><a href="#cite_note-33"><span class="cite-bracket">[</span>33<span class="cite-bracket">]</span></a></sup> </p> <figure class="mw-default-size" typeof="mw:File/Thumb"><a href="/wiki/File:Iron_BBB.jpg" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/0/0c/Iron_BBB.jpg/330px-Iron_BBB.jpg" decoding="async" width="330" height="435" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/0/0c/Iron_BBB.jpg/495px-Iron_BBB.jpg 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/0/0c/Iron_BBB.jpg/660px-Iron_BBB.jpg 2x" data-file-width="700" data-file-height="923" /></a><figcaption>This schematic outlines iron metabolism in the brain illustrating that iron crosses the <a href="/wiki/Blood%E2%80%93brain_barrier" title="Blood–brain barrier">blood–brain barrier</a> either by:<sup id="cite_ref-34" class="reference"><a href="#cite_note-34"><span class="cite-bracket">[</span>34<span class="cite-bracket">]</span></a></sup><div><ul><li>The <a href="/wiki/Transcytosis" title="Transcytosis">transcytosis</a> pathway (illustrated in the upper right segment of the image), where the complex “Fe<sup>3+</sup>-transferrin-transferrin receptor 1 (TfR1)” undergoes endocytosis and exocytosis from the luminal pole to the cerebral <a href="/wiki/Extracellular_matrix" title="Extracellular matrix">extracellular matrix</a> (ECM) and <a href="/wiki/Interstitial_fluid" class="mw-redirect" title="Interstitial fluid">interstitial fluid</a>.</li><li>The facilitated transporter pathway, where <a href="/wiki/Endothelium" title="Endothelium">endothelial cells</a> internalize the complex “Fe<sup>3+</sup>-transferrin-transferrin receptor 1 (TfR1)” in endosome, reduce ferric Fe<sup>3+</sup> ion to ferrous Fe<sup>2+</sup> ion by STEAP3 enzyme and then Fe<sup>2+</sup> ion crosses the endosomal membrane thanks to DMT1. Fe<sup>2+</sup> is then exported to the extracellular matrix (ECM) and interstitial fluid, via ferroportin coupled with ceruloplasmin.</li></ul></div></figcaption></figure> <p>The expression of hepcidin, which only occurs in certain cell types such as <a href="/wiki/Hepatocyte" title="Hepatocyte">hepatocytes</a>, is tightly controlled at the transcriptional level and it represents the link between cellular and systemic iron homeostasis due to hepcidin's role as "gatekeeper" of iron release from enterocytes into the rest of the body.<sup id="cite_ref-Tango_21-4" class="reference"><a href="#cite_note-Tango-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Erythroblasts" class="mw-redirect" title="Erythroblasts">Erythroblasts</a> produce <a href="/wiki/Erythroferrone" title="Erythroferrone">erythroferrone</a>, a hormone which inhibits hepcidin and so increases the availability of iron needed for hemoglobin synthesis.<sup id="cite_ref-pmid24880340_35-0" class="reference"><a href="#cite_note-pmid24880340-35"><span class="cite-bracket">[</span>35<span class="cite-bracket">]</span></a></sup> </p> <div class="mw-heading mw-heading4"><h4 id="Translational_control_of_cellular_iron">Translational control of cellular iron</h4><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=17" title="Edit section: Translational control of cellular iron"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <p>Although some control exists at the transcriptional level, the regulation of cellular iron levels is ultimately controlled at the translational level by <a href="/wiki/Iron-responsive_element-binding_protein" title="Iron-responsive element-binding protein">iron-responsive element-binding proteins</a> IRP1 and especially IRP2.<sup id="cite_ref-36" class="reference"><a href="#cite_note-36"><span class="cite-bracket">[</span>36<span class="cite-bracket">]</span></a></sup> When iron levels are low, these proteins are able to bind to <a href="/wiki/Iron-responsive_element" class="mw-redirect" title="Iron-responsive element">iron-responsive elements</a> (IREs). IREs are stem loop structures in the untranslated regions (UTRs) of mRNA.<sup id="cite_ref-Tango_21-5" class="reference"><a href="#cite_note-Tango-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> </p><p>Both ferritin and ferroportin contain an IRE in their 5' UTRs, so that under iron deficiency their translation is repressed by IRP2, preventing the unnecessary synthesis of storage protein and the detrimental export of iron. In contrast, TFR1 and some DMT1 variants contain 3' UTR IREs, which bind IRP2 under iron deficiency, stabilizing the mRNA, which guarantees the synthesis of iron importers.<sup id="cite_ref-Tango_21-6" class="reference"><a href="#cite_note-Tango-21"><span class="cite-bracket">[</span>21<span class="cite-bracket">]</span></a></sup> </p><p><span class="anchor" id="Iron-related_pathology"></span> </p> <div class="mw-heading mw-heading2"><h2 id="Pathology">Pathology</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=18" title="Edit section: Pathology"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Iron_metabolism_disorder" title="Iron metabolism disorder">Iron metabolism disorder</a></div> <div class="mw-heading mw-heading3"><h3 id="Iron_deficiency">Iron deficiency</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=19" title="Edit section: Iron deficiency"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Iron_deficiency" title="Iron deficiency">Iron deficiency</a></div> <figure class="mw-default-size mw-halign-right" typeof="mw:File/Thumb"><a href="/wiki/File:Pregnant_Woman_With_Dumbells.JPG" class="mw-file-description"><img src="//upload.wikimedia.org/wikipedia/commons/thumb/e/e6/Pregnant_Woman_With_Dumbells.JPG/170px-Pregnant_Woman_With_Dumbells.JPG" decoding="async" width="170" height="254" class="mw-file-element" srcset="//upload.wikimedia.org/wikipedia/commons/thumb/e/e6/Pregnant_Woman_With_Dumbells.JPG/255px-Pregnant_Woman_With_Dumbells.JPG 1.5x, //upload.wikimedia.org/wikipedia/commons/thumb/e/e6/Pregnant_Woman_With_Dumbells.JPG/340px-Pregnant_Woman_With_Dumbells.JPG 2x" data-file-width="700" data-file-height="1044" /></a><figcaption> Iron is an important topic in <a href="/wiki/Prenatal_care" title="Prenatal care">prenatal care</a> because women can sometimes become iron-deficient from the increased iron demands of pregnancy.</figcaption></figure> <p>Functional or actual iron deficiency can result from a variety of causes. These causes can be grouped into several categories: </p> <ul><li>Increased demand for iron, which the diet cannot accommodate.</li> <li>Increased loss of iron (usually through loss of blood).</li> <li>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 <a href="/wiki/Phytates" class="mw-redirect" title="Phytates">phytates</a> in <a href="/wiki/Bran" title="Bran">bran</a>,<sup id="cite_ref-pmid2820048_37-0" class="reference"><a href="#cite_note-pmid2820048-37"><span class="cite-bracket">[</span>37<span class="cite-bracket">]</span></a></sup> <a href="/wiki/Calcium" title="Calcium">calcium</a> from supplements or dairy products,<sup id="cite_ref-pmid19087437_38-0" class="reference"><a href="#cite_note-pmid19087437-38"><span class="cite-bracket">[</span>38<span class="cite-bracket">]</span></a></sup> and <a href="/wiki/Tannins" class="mw-redirect" title="Tannins">tannins</a> from tea,<sup id="cite_ref-pmid1168162_39-0" class="reference"><a href="#cite_note-pmid1168162-39"><span class="cite-bracket">[</span>39<span class="cite-bracket">]</span></a></sup> 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.</li> <li>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), <a href="/wiki/H2_antagonist" class="mw-redirect" title="H2 antagonist">H2 antihistamines</a>, and antacids will reduce iron metabolism.<sup id="cite_ref-40" class="reference"><a href="#cite_note-40"><span class="cite-bracket">[</span>40<span class="cite-bracket">]</span></a></sup></li> <li>Damage to the intestinal lining. Examples of causes of this kind of damage include surgery involving the duodenum or diseases like <a href="/wiki/Crohn%27s" class="mw-redirect" title="Crohn's">Crohn's</a> or <a href="/wiki/Celiac_sprue" class="mw-redirect" title="Celiac sprue">celiac sprue</a> which severely reduce the surface area available for absorption. <i><a href="/wiki/Helicobacter_pylori" title="Helicobacter pylori">Helicobacter pylori</a></i> infections also reduce the availability of iron.<sup id="cite_ref-41" class="reference"><a href="#cite_note-41"><span class="cite-bracket">[</span>41<span class="cite-bracket">]</span></a></sup></li> <li>Inflammation leading to hepcidin-induced restriction on iron release from enterocytes (see above).</li> <li>Is also a common occurrence in pregnant women, and in growing adolescents due to poor diets.</li> <li>Acute blood loss or acute liver cirrhosis creates a lack of transferrin therefore causing iron to be secreted from the body.</li></ul> <div class="mw-heading mw-heading3"><h3 id="Iron_overload">Iron overload</h3><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=20" title="Edit section: Iron overload"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236090951"><div role="note" class="hatnote navigation-not-searchable">Main article: <a href="/wiki/Iron_overload" title="Iron overload">Iron overload</a></div> <p>The body is able to substantially reduce the amount of iron it absorbs across the mucosa. It does not seem to be able to entirely shut down the iron transport process. Also, in situations where excess iron damages the intestinal lining itself (for instance, when children eat a large quantity of iron tablets produced for adult consumption), even more iron can enter the bloodstream and cause a potentially deadly syndrome of iron overload. Large amounts of free iron in the circulation will cause damage to critical cells in the liver, the <a href="/wiki/Heart" title="Heart">heart</a> and other metabolically active organs. </p><p>Iron toxicity results when the amount of circulating iron exceeds the amount of transferrin available to bind it, but the body is able to vigorously regulate its iron uptake. Thus, iron toxicity from ingestion is usually the result of extraordinary circumstances like iron tablet over-consumption<sup class="plainlinks nourlexpansion citation" id="ref_Baker"><a class="external autonumber" href="https://en.wikipedia.org/wiki/Human_iron_metabolism#endnote_Baker">[1]</a></sup><sup id="cite_ref-isbn0-07-112457-8_42-0" class="reference"><a href="#cite_note-isbn0-07-112457-8-42"><span class="cite-bracket">[</span>42<span class="cite-bracket">]</span></a></sup> rather than variations in <a href="/wiki/Diet_(nutrition)" title="Diet (nutrition)">diet</a>. The type of acute toxicity from iron ingestion causes severe mucosal damage in the gastrointestinal tract, among other problems. </p><p>Excess iron has been linked to higher rates of disease and mortality. For example, breast cancer patients with low <a href="/wiki/Ferroportin" title="Ferroportin">ferroportin</a> expression (leading to higher concentrations of intracellular iron) survive for a shorter period of time on average, while high ferroportin expression predicts 90% 10-year survival in breast cancer patients.<sup id="cite_ref-43" class="reference"><a href="#cite_note-43"><span class="cite-bracket">[</span>43<span class="cite-bracket">]</span></a></sup> Similarly, genetic variations in iron transporter genes known to increase serum iron levels also reduce <a href="/wiki/Life_expectancy" title="Life expectancy">lifespan</a> and the average number of years spent in good health.<sup id="cite_ref-Timmers_44-0" class="reference"><a href="#cite_note-Timmers-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup> It has been suggested that mutations that increase iron absorption, such as the ones responsible for hemochromatosis (see below), were selected for during <a href="/wiki/Neolithic" title="Neolithic">Neolithic</a> times as they provided a <a href="/wiki/Selective_advantage" class="mw-redirect" title="Selective advantage">selective advantage</a> against iron-deficiency anemia.<sup id="cite_ref-45" class="reference"><a href="#cite_note-45"><span class="cite-bracket">[</span>45<span class="cite-bracket">]</span></a></sup> The increase in systemic iron levels becomes pathological in old age, which supports the notion that <a href="/wiki/Antagonistic_pleiotropy" class="mw-redirect" title="Antagonistic pleiotropy">antagonistic pleiotropy</a> or "hyperfunction" drives human aging.<sup id="cite_ref-Timmers_44-1" class="reference"><a href="#cite_note-Timmers-44"><span class="cite-bracket">[</span>44<span class="cite-bracket">]</span></a></sup> </p><p>Chronic iron toxicity is usually the result of more chronic iron overload syndromes associated with genetic diseases, repeated transfusions or other causes. In such cases the iron stores of an adult may reach 50 grams (10 times normal total body iron) or more. The most common diseases of iron overload are <a href="/wiki/Hereditary_hemochromatosis" class="mw-redirect" title="Hereditary hemochromatosis">hereditary hemochromatosis</a> (HH), caused by mutations in the <i><a href="/wiki/HFE_(gene)" title="HFE (gene)">HFE</a></i> gene, and the more severe disease <a href="/wiki/Juvenile_hemochromatosis" title="Juvenile hemochromatosis">juvenile hemochromatosis</a> (JH), caused by mutations in either <a href="/wiki/Hemojuvelin" title="Hemojuvelin">hemojuvelin</a> (<i>HJV</i>)<sup id="cite_ref-pmid19698085_46-0" class="reference"><a href="#cite_note-pmid19698085-46"><span class="cite-bracket">[</span>46<span class="cite-bracket">]</span></a></sup> or hepcidin (<i>HAMP</i>). The exact mechanisms of most of the various forms of adult hemochromatosis, which make up most of the genetic iron overload disorders, remain unsolved. So, while researchers have been able to identify genetic mutations causing several adult variants of hemochromatosis, they now must turn their attention to the normal function of these mutated genes. </p> <div class="mw-heading mw-heading2"><h2 id="See_also">See also</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=21" title="Edit section: See also"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a href="/wiki/Iron_in_biology" title="Iron in biology">Iron in biology</a></li></ul> <div class="mw-heading mw-heading2"><h2 id="References">References</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=22" title="Edit section: References"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239543626">.mw-parser-output .reflist{margin-bottom:0.5em;list-style-type:decimal}@media screen{.mw-parser-output .reflist{font-size:90%}}.mw-parser-output .reflist .references{font-size:100%;margin-bottom:0;list-style-type:inherit}.mw-parser-output .reflist-columns-2{column-width:30em}.mw-parser-output .reflist-columns-3{column-width:25em}.mw-parser-output .reflist-columns{margin-top:0.3em}.mw-parser-output .reflist-columns ol{margin-top:0}.mw-parser-output .reflist-columns li{page-break-inside:avoid;break-inside:avoid-column}.mw-parser-output .reflist-upper-alpha{list-style-type:upper-alpha}.mw-parser-output .reflist-upper-roman{list-style-type:upper-roman}.mw-parser-output .reflist-lower-alpha{list-style-type:lower-alpha}.mw-parser-output .reflist-lower-greek{list-style-type:lower-greek}.mw-parser-output .reflist-lower-roman{list-style-type:lower-roman}</style><div class="reflist reflist-columns references-column-width" style="column-width: 33em;"> <ol class="references"> <li id="cite_note-pmid10787338-1"><span class="mw-cite-backlink">^ <a href="#cite_ref-pmid10787338_1-0"><sup><i><b>a</b></i></sup></a> <a href="#cite_ref-pmid10787338_1-1"><sup><i><b>b</b></i></sup></a> <a href="#cite_ref-pmid10787338_1-2"><sup><i><b>c</b></i></sup></a></span> <span class="reference-text"><style data-mw-deduplicate="TemplateStyles:r1238218222">.mw-parser-output cite.citation{font-style:inherit;word-wrap:break-word}.mw-parser-output .citation q{quotes:"\"""\"""'""'"}.mw-parser-output .citation:target{background-color:rgba(0,127,255,0.133)}.mw-parser-output .id-lock-free.id-lock-free a{background:url("//upload.wikimedia.org/wikipedia/commons/6/65/Lock-green.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-limited.id-lock-limited a,.mw-parser-output .id-lock-registration.id-lock-registration a{background:url("//upload.wikimedia.org/wikipedia/commons/d/d6/Lock-gray-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .id-lock-subscription.id-lock-subscription a{background:url("//upload.wikimedia.org/wikipedia/commons/a/aa/Lock-red-alt-2.svg")right 0.1em center/9px no-repeat}.mw-parser-output .cs1-ws-icon a{background:url("//upload.wikimedia.org/wikipedia/commons/4/4c/Wikisource-logo.svg")right 0.1em center/12px no-repeat}body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-free a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-limited a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-registration a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .id-lock-subscription a,body:not(.skin-timeless):not(.skin-minerva) .mw-parser-output .cs1-ws-icon a{background-size:contain;padding:0 1em 0 0}.mw-parser-output .cs1-code{color:inherit;background:inherit;border:none;padding:inherit}.mw-parser-output .cs1-hidden-error{display:none;color:var(--color-error,#d33)}.mw-parser-output .cs1-visible-error{color:var(--color-error,#d33)}.mw-parser-output .cs1-maint{display:none;color:#085;margin-left:0.3em}.mw-parser-output .cs1-kern-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right{padding-right:0.2em}.mw-parser-output .citation .mw-selflink{font-weight:inherit}@media screen{.mw-parser-output .cs1-format{font-size:95%}html.skin-theme-clientpref-night .mw-parser-output .cs1-maint{color:#18911f}}@media screen and (prefers-color-scheme:dark){html.skin-theme-clientpref-os .mw-parser-output .cs1-maint{color:#18911f}}</style><cite id="CITEREFConradUmbreit2000" class="citation journal cs1">Conrad ME, Umbreit JN (Apr 2000). 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J.; Wilson, James F.; Joshi, Peter K.; Deelen, Joris (Jul 2020). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366647">"Multivariate genomic scan implicates novel loci and haem metabolism in human ageing"</a>. <i>Nature Communications</i>. <b>11</b> (3570): 3570. <a href="/wiki/Bibcode_(identifier)" class="mw-redirect" title="Bibcode (identifier)">Bibcode</a>:<a rel="nofollow" class="external text" href="https://ui.adsabs.harvard.edu/abs/2020NatCo..11.3570T">2020NatCo..11.3570T</a>. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1038%2Fs41467-020-17312-3">10.1038/s41467-020-17312-3</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7366647">7366647</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/32678081">32678081</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Nature+Communications&rft.atitle=Multivariate+genomic+scan+implicates+novel+loci+and+haem+metabolism+in+human+ageing&rft.volume=11&rft.issue=3570&rft.pages=3570&rft.date=2020-07&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC7366647%23id-name%3DPMC&rft_id=info%3Apmid%2F32678081&rft_id=info%3Adoi%2F10.1038%2Fs41467-020-17312-3&rft_id=info%3Abibcode%2F2020NatCo..11.3570T&rft.aulast=Timmers&rft.aufirst=Paul+R.+H.+J.&rft.au=Wilson%2C+James+F.&rft.au=Joshi%2C+Peter+K.&rft.au=Deelen%2C+Joris&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC7366647&rfr_id=info%3Asid%2Fen.wikipedia.org%3AHuman+iron+metabolism" class="Z3988"></span></span> </li> <li id="cite_note-45"><span class="mw-cite-backlink"><b><a href="#cite_ref-45">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFRamettaMeroniDongiovanni2020" class="citation journal cs1">Rametta, Raffaela; Meroni, Marica; Dongiovanni, Paola (15 May 2020). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279025">"From Environment to Genome and Back: A Lesson from HFE Mutations"</a>. <i>International Journal of Molecular Sciences</i>. <b>21</b> (10): 3505. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.3390%2Fijms21103505">10.3390/ijms21103505</a></span>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279025">7279025</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/32429125">32429125</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=International+Journal+of+Molecular+Sciences&rft.atitle=From+Environment+to+Genome+and+Back%3A+A+Lesson+from+HFE+Mutations&rft.volume=21&rft.issue=10&rft.pages=3505&rft.date=2020-05-15&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC7279025%23id-name%3DPMC&rft_id=info%3Apmid%2F32429125&rft_id=info%3Adoi%2F10.3390%2Fijms21103505&rft.aulast=Rametta&rft.aufirst=Raffaela&rft.au=Meroni%2C+Marica&rft.au=Dongiovanni%2C+Paola&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC7279025&rfr_id=info%3Asid%2Fen.wikipedia.org%3AHuman+iron+metabolism" class="Z3988"></span></span> </li> <li id="cite_note-pmid19698085-46"><span class="mw-cite-backlink"><b><a href="#cite_ref-pmid19698085_46-0">^</a></b></span> <span class="reference-text"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFSeverynShindeRotwein2009" class="citation journal cs1">Severyn CJ, Shinde U, Rotwein P (Sep 2009). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242795">"Molecular biology, genetics and biochemistry of the repulsive guidance molecule family"</a>. <i>The Biochemical Journal</i>. <b>422</b> (3): 393–403. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1042%2FBJ20090978">10.1042/BJ20090978</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4242795">4242795</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/19698085">19698085</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=The+Biochemical+Journal&rft.atitle=Molecular+biology%2C+genetics+and+biochemistry+of+the+repulsive+guidance+molecule+family&rft.volume=422&rft.issue=3&rft.pages=393-403&rft.date=2009-09&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC4242795%23id-name%3DPMC&rft_id=info%3Apmid%2F19698085&rft_id=info%3Adoi%2F10.1042%2FBJ20090978&rft.aulast=Severyn&rft.aufirst=CJ&rft.au=Shinde%2C+U&rft.au=Rotwein%2C+P&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC4242795&rfr_id=info%3Asid%2Fen.wikipedia.org%3AHuman+iron+metabolism" class="Z3988"></span></span> </li> </ol></div> <div class="mw-heading mw-heading2"><h2 id="Further_reading">Further reading</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=23" title="Edit section: Further reading"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <style data-mw-deduplicate="TemplateStyles:r1239549316">.mw-parser-output .refbegin{margin-bottom:0.5em}.mw-parser-output .refbegin-hanging-indents>ul{margin-left:0}.mw-parser-output .refbegin-hanging-indents>ul>li{margin-left:0;padding-left:3.2em;text-indent:-3.2em}.mw-parser-output .refbegin-hanging-indents ul,.mw-parser-output .refbegin-hanging-indents ul li{list-style:none}@media(max-width:720px){.mw-parser-output .refbegin-hanging-indents>ul>li{padding-left:1.6em;text-indent:-1.6em}}.mw-parser-output .refbegin-columns{margin-top:0.3em}.mw-parser-output .refbegin-columns ul{margin-top:0}.mw-parser-output .refbegin-columns li{page-break-inside:avoid;break-inside:avoid-column}@media screen{.mw-parser-output .refbegin{font-size:90%}}</style><div class="refbegin refbegin-columns references-column-width" style="column-width: 33em"> <ul><li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFAndrewsNortonSalunkheGoodluck2013" class="citation book cs1">Andrews S, Norton I, Salunkhe AS, Goodluck H, Aly WS, Mourad-Agha H, Cornelis P (2013). "Chapter 7, Control of Iron Metabolism in Bacteria". In Banci L (ed.). <i>Metallomics and the Cell</i>. Metal Ions in Life Sciences. Vol. 12. Springer. pp. 203–39. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1007%2F978-94-007-5561-1_7">10.1007/978-94-007-5561-1_7</a>. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-94-007-5560-4" title="Special:BookSources/978-94-007-5560-4"><bdi>978-94-007-5560-4</bdi></a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/23595674">23595674</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.atitle=Chapter+7%2C+Control+of+Iron+Metabolism+in+Bacteria&rft.btitle=Metallomics+and+the+Cell&rft.series=Metal+Ions+in+Life+Sciences&rft.pages=203-39&rft.pub=Springer&rft.date=2013&rft_id=info%3Apmid%2F23595674&rft_id=info%3Adoi%2F10.1007%2F978-94-007-5561-1_7&rft.isbn=978-94-007-5560-4&rft.aulast=Andrews&rft.aufirst=Simon&rft.au=Norton%2C+Ian&rft.au=Salunkhe%2C+Arvindkumar+S.&rft.au=Goodluck%2C+Helen&rft.au=Aly%2C+Wafaa+S.M.&rft.au=Mourad-Agha%2C+Hanna&rft.au=Cornelis%2C+Pierre&rfr_id=info%3Asid%2Fen.wikipedia.org%3AHuman+iron+metabolism" class="Z3988"></span> electronic-book <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-94-007-5561-1" title="Special:BookSources/978-94-007-5561-1">978-94-007-5561-1</a> <link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><a href="/wiki/ISSN_(identifier)" class="mw-redirect" title="ISSN (identifier)">ISSN</a> <a rel="nofollow" class="external text" href="https://www.worldcat.org/search?fq=x0:jrnl&q=n2:1559-0836">1559-0836</a> electronic-<link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><a href="/wiki/ISSN_(identifier)" class="mw-redirect" title="ISSN (identifier)">ISSN</a> <a rel="nofollow" class="external text" href="https://www.worldcat.org/search?fq=x0:jrnl&q=n2:1868-0402">1868-0402</a></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFAndrews2004" class="citation journal cs1">Andrews NC (May 2004). <a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC398435">"Anemia of inflammation: the cytokine-hepcidin link"</a>. <i>The Journal of Clinical Investigation</i>. <b>113</b> (9): 1251–3. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1172%2FJCI21441">10.1172/JCI21441</a>. <a href="/wiki/PMC_(identifier)" class="mw-redirect" title="PMC (identifier)">PMC</a> <span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC398435">398435</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/15124013">15124013</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=The+Journal+of+Clinical+Investigation&rft.atitle=Anemia+of+inflammation%3A+the+cytokine-hepcidin+link&rft.volume=113&rft.issue=9&rft.pages=1251-3&rft.date=2004-05&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC398435%23id-name%3DPMC&rft_id=info%3Apmid%2F15124013&rft_id=info%3Adoi%2F10.1172%2FJCI21441&rft.aulast=Andrews&rft.aufirst=NC&rft_id=https%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC398435&rfr_id=info%3Asid%2Fen.wikipedia.org%3AHuman+iron+metabolism" class="Z3988"></span></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFCamaschella2005" class="citation journal cs1">Camaschella C (Dec 2005). <a rel="nofollow" class="external text" href="https://doi.org/10.1182%2Fblood-2005-05-1857">"Understanding iron homeostasis through genetic analysis of hemochromatosis and related disorders"</a>. <i>Blood</i>. <b>106</b> (12): 3710–7. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<span class="id-lock-free" title="Freely accessible"><a rel="nofollow" class="external text" href="https://doi.org/10.1182%2Fblood-2005-05-1857">10.1182/blood-2005-05-1857</a></span>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/16030190">16030190</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=Blood&rft.atitle=Understanding+iron+homeostasis+through+genetic+analysis+of+hemochromatosis+and+related+disorders&rft.volume=106&rft.issue=12&rft.pages=3710-7&rft.date=2005-12&rft_id=info%3Adoi%2F10.1182%2Fblood-2005-05-1857&rft_id=info%3Apmid%2F16030190&rft.aulast=Camaschella&rft.aufirst=C&rft_id=https%3A%2F%2Fdoi.org%2F10.1182%252Fblood-2005-05-1857&rfr_id=info%3Asid%2Fen.wikipedia.org%3AHuman+iron+metabolism" class="Z3988"></span></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFFrazerAnderson2005" class="citation journal cs1">Frazer DM, Anderson GJ (Oct 2005). "Iron imports. I. Intestinal iron absorption and its regulation". <i>American Journal of Physiology. Gastrointestinal and Liver Physiology</i>. <b>289</b> (4): G631–5. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1152%2Fajpgi.00220.2005">10.1152/ajpgi.00220.2005</a>. <a href="/wiki/PMID_(identifier)" class="mw-redirect" title="PMID (identifier)">PMID</a> <a rel="nofollow" class="external text" href="https://pubmed.ncbi.nlm.nih.gov/16160078">16160078</a>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.jtitle=American+Journal+of+Physiology.+Gastrointestinal+and+Liver+Physiology&rft.atitle=Iron+imports.+I.+Intestinal+iron+absorption+and+its+regulation&rft.volume=289&rft.issue=4&rft.pages=G631-5&rft.date=2005-10&rft_id=info%3Adoi%2F10.1152%2Fajpgi.00220.2005&rft_id=info%3Apmid%2F16160078&rft.aulast=Frazer&rft.aufirst=DM&rft.au=Anderson%2C+GJ&rfr_id=info%3Asid%2Fen.wikipedia.org%3AHuman+iron+metabolism" class="Z3988"></span></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFInselRossMcMahonBernstein2011" class="citation book cs1">Insel P, Ross D, McMahon K, Bernstein M (2011). <a rel="nofollow" class="external text" href="https://books.google.com/books?id=u1p_G8CJ-mwC&pg=PA510">"Iron"</a>. <i>Nutrition</i> (4th ed.). Sudbury, Massachusetts: <a href="/wiki/Jones_and_Bartlett_Publishers" class="mw-redirect" title="Jones and Bartlett Publishers">Jones and Bartlett Publishers</a>. pp. 510–514. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-0-7637-7663-3" title="Special:BookSources/978-0-7637-7663-3"><bdi>978-0-7637-7663-3</bdi></a><span class="reference-accessdate">. Retrieved <span class="nowrap">June 25,</span> 2012</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.atitle=Iron&rft.btitle=Nutrition&rft.place=Sudbury%2C+Massachusetts&rft.pages=510-514&rft.edition=4th&rft.pub=Jones+and+Bartlett+Publishers&rft.date=2011&rft.isbn=978-0-7637-7663-3&rft.aulast=Insel&rft.aufirst=P&rft.au=Ross%2C+D&rft.au=McMahon%2C+K&rft.au=Bernstein%2C+M&rft_id=https%3A%2F%2Fbooks.google.com%2Fbooks%3Fid%3Du1p_G8CJ-mwC%26pg%3DPA510&rfr_id=info%3Asid%2Fen.wikipedia.org%3AHuman+iron+metabolism" class="Z3988"></span> See esp. pp. 513-514.</li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFLammi-KeefCouchPhilipson2008" class="citation book cs1">Lammi-Keef CJ, Couch SC, Philipson EH, eds. (2008). <a rel="nofollow" class="external text" href="https://books.google.com/books?id=29EhDBLoPGEC&pg=PA350">"Dietary diversification and modification of iron"</a>. <i>Handbook of Nutrition and Pregnancy</i>. Nutrition & Health. Totowa, New Jersey: <a href="/wiki/Humana_Press" title="Humana Press">Humana Press</a>. pp. 350–351. <a href="/wiki/Doi_(identifier)" class="mw-redirect" title="Doi (identifier)">doi</a>:<a rel="nofollow" class="external text" href="https://doi.org/10.1007%2F978-1-59745-112-3">10.1007/978-1-59745-112-3</a>. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-1-59745-112-3" title="Special:BookSources/978-1-59745-112-3"><bdi>978-1-59745-112-3</bdi></a><span class="reference-accessdate">. Retrieved <span class="nowrap">June 25,</span> 2012</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.atitle=Dietary+diversification+and+modification+of+iron&rft.btitle=Handbook+of+Nutrition+and+Pregnancy&rft.place=Totowa%2C+New+Jersey&rft.series=Nutrition+%26+Health&rft.pages=350-351&rft.pub=Humana+Press&rft.date=2008&rft_id=info%3Adoi%2F10.1007%2F978-1-59745-112-3&rft.isbn=978-1-59745-112-3&rft_id=https%3A%2F%2Fbooks.google.com%2Fbooks%3Fid%3D29EhDBLoPGEC%26pg%3DPA350&rfr_id=info%3Asid%2Fen.wikipedia.org%3AHuman+iron+metabolism" class="Z3988"></span></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFPanel_on_MicronutrientsSubcommittees_on_Upper_Reference_Levels_of_Nutrients_and_of_Interpretation_and_Uses_of_Dietary_Reference_Intakesthe_Standing_Committee_on_the_Scientific_Evaluation_of_Dietary_Reference_Intakes2001" class="citation book cs1">Panel on Micronutrients; Subcommittees on Upper Reference Levels of Nutrients and of Interpretation and Uses of Dietary Reference Intakes; the Standing Committee on the Scientific Evaluation of Dietary Reference Intakes (2001). <a rel="nofollow" class="external text" href="http://books.nap.edu/openbook.php?record_id=10026&page=290">"Iron"</a>. <i>Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc</i>. Washington, D.C.: Food and Nutrition Board, <a href="/wiki/Institute_of_Medicine" class="mw-redirect" title="Institute of Medicine">Institute of Medicine</a>. pp. 290–393. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-0-309-07279-3" title="Special:BookSources/978-0-309-07279-3"><bdi>978-0-309-07279-3</bdi></a><span class="reference-accessdate">. Retrieved <span class="nowrap">June 25,</span> 2012</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.atitle=Iron&rft.btitle=Dietary+Reference+Intakes+for+Vitamin+A%2C+Vitamin+K%2C+Arsenic%2C+Boron%2C+Chromium%2C+Copper%2C+Iodine%2C+Iron%2C+Manganese%2C+Molybdenum%2C+Nickel%2C+Silicon%2C+Vanadium%2C+and+Zinc&rft.place=Washington%2C+D.C.&rft.pages=290-393&rft.pub=Food+and+Nutrition+Board%2C+Institute+of+Medicine&rft.date=2001&rft.isbn=978-0-309-07279-3&rft.au=Panel+on+Micronutrients&rft.au=Subcommittees+on+Upper+Reference+Levels+of+Nutrients+and+of+Interpretation+and+Uses+of+Dietary+Reference+Intakes&rft.au=the+Standing+Committee+on+the+Scientific+Evaluation+of+Dietary+Reference+Intakes&rft_id=http%3A%2F%2Fbooks.nap.edu%2Fopenbook.php%3Frecord_id%3D10026%26page%3D290&rfr_id=info%3Asid%2Fen.wikipedia.org%3AHuman+iron+metabolism" class="Z3988"></span></li> <li><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1238218222"><cite id="CITEREFReilly_C2004" class="citation book cs1">Reilly C (2004). <a rel="nofollow" class="external text" href="https://books.google.com/books?id=825s4l-wS6AC">"Iron"</a>. <i>The Nutritional Trace Metals</i>. Oxford, UK & Ames, Iowa: <a href="/wiki/Blackwell_Publishing" class="mw-redirect" title="Blackwell Publishing">Blackwell Publishing</a>. pp. 35–81. <a href="/wiki/ISBN_(identifier)" class="mw-redirect" title="ISBN (identifier)">ISBN</a> <a href="/wiki/Special:BookSources/978-1-4051-1040-2" title="Special:BookSources/978-1-4051-1040-2"><bdi>978-1-4051-1040-2</bdi></a><span class="reference-accessdate">. Retrieved <span class="nowrap">June 25,</span> 2012</span>.</cite><span title="ctx_ver=Z39.88-2004&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook&rft.genre=bookitem&rft.atitle=Iron&rft.btitle=The+Nutritional+Trace+Metals&rft.place=Oxford%2C+UK+%26+Ames%2C+Iowa&rft.pages=35-81&rft.pub=Blackwell+Publishing&rft.date=2004&rft.isbn=978-1-4051-1040-2&rft.au=Reilly+C&rft_id=https%3A%2F%2Fbooks.google.com%2Fbooks%3Fid%3D825s4l-wS6AC&rfr_id=info%3Asid%2Fen.wikipedia.org%3AHuman+iron+metabolism" class="Z3988"></span></li></ul> </div> <div class="mw-heading mw-heading2"><h2 id="External_links">External links</h2><span class="mw-editsection"><span class="mw-editsection-bracket">[</span><a href="/w/index.php?title=Human_iron_metabolism&action=edit&section=24" title="Edit section: External links"><span>edit</span></a><span class="mw-editsection-bracket">]</span></span></div> <ul><li><a rel="nofollow" class="external text" href="http://ods.od.nih.gov/factsheets/iron.asp">A comprehensive NIH factsheet on iron and nutrition</a></li> <li><a rel="nofollow" class="external text" href="http://www.irondisorders.org">Iron Disorders Institute: A nonprofit group concerned with iron disorders; site has helpful links and information on iron-related medical disorders.</a></li> <li><a rel="nofollow" class="external text" href="http://www.ironatlas.com">An interactive medical learning portal on iron metabolism</a></li> <li><a rel="nofollow" class="external text" href="http://www.webelements.com/iron/">Information about iron outside the body</a></li></ul> <div class="navbox-styles"><style data-mw-deduplicate="TemplateStyles:r1129693374">.mw-parser-output .hlist dl,.mw-parser-output .hlist ol,.mw-parser-output .hlist ul{margin:0;padding:0}.mw-parser-output .hlist dd,.mw-parser-output .hlist dt,.mw-parser-output .hlist li{margin:0;display:inline}.mw-parser-output .hlist.inline,.mw-parser-output .hlist.inline dl,.mw-parser-output .hlist.inline ol,.mw-parser-output .hlist.inline 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template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Metabolism" title="Template talk:Metabolism"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Metabolism" title="Special:EditPage/Template:Metabolism"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Metabolism,_catabolism,_anabolism" style="font-size:114%;margin:0 4em"><a href="/wiki/Metabolism" title="Metabolism">Metabolism</a>, <a href="/wiki/Catabolism" title="Catabolism">catabolism</a>, <a href="/wiki/Anabolism" title="Anabolism">anabolism</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%">General</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Metabolic_pathway" title="Metabolic pathway">Metabolic pathway</a></li> <li><a href="/wiki/Metabolic_network" title="Metabolic network">Metabolic network</a></li> <li><a href="/wiki/Primary_nutritional_groups" title="Primary nutritional groups">Primary nutritional groups</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Bioenergetics" title="Bioenergetics">Energy<br /> metabolism</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Aerobic_respiration" class="mw-redirect" title="Aerobic respiration">Aerobic respiration</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Glycolysis" title="Glycolysis">Glycolysis</a> → <a href="/wiki/Pyruvate_dehydrogenase" title="Pyruvate dehydrogenase">Pyruvate decarboxylation</a> → <a href="/wiki/Citric_acid_cycle" title="Citric acid cycle">Citric acid cycle</a> → <a href="/wiki/Oxidative_phosphorylation" title="Oxidative phosphorylation">Oxidative phosphorylation</a> (<span style="font-size:85%;"><a href="/wiki/Electron_transport_chain" title="Electron transport chain">electron transport chain</a> + <a href="/wiki/ATP_synthase" title="ATP synthase">ATP synthase</a></span>)</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Anaerobic_respiration" title="Anaerobic respiration">Anaerobic respiration</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li>Electron acceptors other than oxygen</li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Fermentation" title="Fermentation">Fermentation</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Glycolysis" title="Glycolysis">Glycolysis</a> → <a href="/wiki/Substrate-level_phosphorylation" title="Substrate-level phosphorylation">Substrate-level phosphorylation</a> <ul><li><a href="/wiki/Acetone%E2%80%93butanol%E2%80%93ethanol_fermentation" title="Acetone–butanol–ethanol fermentation">ABE</a></li> <li><a href="/wiki/Ethanol_fermentation" title="Ethanol fermentation">Ethanol</a></li> <li><a href="/wiki/Lactic_acid_fermentation" title="Lactic acid fermentation">Lactic acid</a></li></ul></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Specific<br /> paths</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Protein_metabolism" title="Protein metabolism">Protein metabolism</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Protein_biosynthesis" title="Protein biosynthesis">Protein synthesis</a></li> <li><a href="/wiki/Protein_catabolism" title="Protein catabolism">Catabolism</a> (protein→peptide→amino acid)</li></ul> </div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Amino_acid" title="Amino acid">Amino acid</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Amino_acid_synthesis" title="Amino acid synthesis">Amino acid synthesis</a></li> <li><a href="/wiki/Protein_catabolism#Amino_acid_degradation" title="Protein catabolism">Amino acid degradation</a> (amino acid→pyruvate, acetyl CoA, or TCA intermediate)</li> <li><a href="/wiki/Urea_cycle" title="Urea cycle">Urea cycle</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Nucleic_acid_metabolism" title="Nucleic acid metabolism">Nucleotide<br /> metabolism</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Purine_metabolism" title="Purine metabolism">Purine metabolism</a></li> <li><a href="/wiki/Nucleotide_salvage" title="Nucleotide salvage">Nucleotide salvage</a></li> <li><a href="/wiki/Pyrimidine_metabolism" title="Pyrimidine metabolism">Pyrimidine metabolism</a></li> <li><a href="/wiki/Purine_nucleotide_cycle" title="Purine nucleotide cycle">Purine nucleotide cycle</a></li></ul> </div></td></tr></tbody></table><div> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Carbohydrate_metabolism" title="Carbohydrate metabolism">Carbohydrate metabolism</a><br />(<a href="/wiki/Carbohydrate_catabolism" title="Carbohydrate catabolism">carbohydrate catabolism</a><br />and <a href="/wiki/Anabolism" title="Anabolism">anabolism</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%">Human</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><td colspan="2" class="navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Glycolysis" title="Glycolysis">Glycolysis</a> ⇄ <a href="/wiki/Gluconeogenesis" title="Gluconeogenesis">Gluconeogenesis</a></li></ul> </div></td></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Glycogenolysis" title="Glycogenolysis">Glycogenolysis</a> ⇄ <a href="/wiki/Glycogenesis" title="Glycogenesis">Glycogenesis</a></li></ul> </div></td></tr><tr><td colspan="2" class="navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Pentose_phosphate_pathway" title="Pentose phosphate pathway">Pentose phosphate pathway</a></li> <li><a href="/wiki/Fructolysis" title="Fructolysis">Fructolysis</a> <ul><li><a href="/wiki/Polyol_pathway" title="Polyol pathway">Polyol pathway</a></li></ul></li> <li><a href="/wiki/Galactolysis" title="Galactolysis">Galactolysis</a> <ul><li><a href="/wiki/Leloir_pathway" title="Leloir pathway">Leloir pathway</a></li></ul></li></ul> </div></td></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Glycosylation" title="Glycosylation">Glycosylation</a> <ul><li><a href="/wiki/N-linked_glycosylation" title="N-linked glycosylation">N-linked</a></li> <li><a href="/wiki/O-linked_glycosylation" title="O-linked glycosylation">O-linked</a></li></ul></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Nonhuman</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><td colspan="2" class="navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Photosynthesis" title="Photosynthesis">Photosynthesis</a></li> <li><a href="/wiki/Anoxygenic_photosynthesis" title="Anoxygenic photosynthesis">Anoxygenic photosynthesis</a></li> <li><a href="/wiki/Chemosynthesis" title="Chemosynthesis">Chemosynthesis</a></li> <li><a href="/wiki/Carbon_fixation" class="mw-redirect" title="Carbon fixation">Carbon fixation</a></li> <li><a href="/w/index.php?title=DeLey-Doudoroff_pathway&action=edit&redlink=1" class="new" title="DeLey-Doudoroff pathway (page does not exist)">DeLey-Doudoroff pathway</a></li> <li><a href="/wiki/Entner-Doudoroff_pathway" class="mw-redirect" title="Entner-Doudoroff pathway">Entner-Doudoroff pathway</a></li></ul> </div></td></tr><tr><td colspan="2" class="navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Xylose_metabolism" title="Xylose metabolism">Xylose metabolism</a></li> <li><a href="/wiki/Radiotrophic_fungus" title="Radiotrophic fungus">Radiotrophism</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Lipid_metabolism" title="Lipid metabolism">Lipid metabolism</a> <br />(<a href="/wiki/Lipolysis" title="Lipolysis">lipolysis</a>, <a href="/wiki/Lipogenesis" title="Lipogenesis">lipogenesis</a>)</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Fatty_acid_metabolism" title="Fatty acid metabolism">Fatty acid metabolism</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Fatty_acid_degradation" title="Fatty acid degradation">Fatty acid degradation</a> (<a href="/wiki/Beta_oxidation" title="Beta oxidation">Beta oxidation</a>)</li> <li><a href="/wiki/Fatty_acid_synthesis" title="Fatty acid synthesis">Fatty acid synthesis</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Steroid" title="Steroid">Steroid metabolism</a></li> <li><a href="/wiki/Sphingolipid_metabolism" class="mw-redirect" title="Sphingolipid metabolism">Sphingolipid metabolism</a></li> <li><a href="/wiki/Eicosanoid_metabolism" class="mw-redirect" title="Eicosanoid metabolism">Eicosanoid metabolism</a></li> <li><a href="/wiki/Ketosis" title="Ketosis">Ketosis</a></li> <li><a href="/wiki/Reverse_cholesterol_transport" title="Reverse cholesterol transport">Reverse cholesterol transport</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Bioinorganic_chemistry" title="Bioinorganic chemistry">Metal metabolism</a> <ul><li><a class="mw-selflink selflink">Iron metabolism</a></li></ul></li> <li><a href="/wiki/Ethanol_metabolism" class="mw-redirect" title="Ethanol metabolism">Ethanol metabolism</a></li> <li><a href="/wiki/Phosphagen" title="Phosphagen">Phospagen system (ATP-PCr)</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table></div> <div class="navbox-styles"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1236075235"></div><div role="navigation" class="navbox" aria-labelledby="Metabolism:_Metal_metabolism" style="padding:3px"><table class="nowraplinks mw-collapsible autocollapse navbox-inner" style="border-spacing:0;background:transparent;color:inherit"><tbody><tr><th scope="col" class="navbox-title" colspan="2"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1129693374"><link rel="mw-deduplicated-inline-style" href="mw-data:TemplateStyles:r1239400231"><div class="navbar plainlinks hlist navbar-mini"><ul><li class="nv-view"><a href="/wiki/Template:Metal_metabolism" title="Template:Metal metabolism"><abbr title="View this template">v</abbr></a></li><li class="nv-talk"><a href="/wiki/Template_talk:Metal_metabolism" title="Template talk:Metal metabolism"><abbr title="Discuss this template">t</abbr></a></li><li class="nv-edit"><a href="/wiki/Special:EditPage/Template:Metal_metabolism" title="Special:EditPage/Template:Metal metabolism"><abbr title="Edit this template">e</abbr></a></li></ul></div><div id="Metabolism:_Metal_metabolism" style="font-size:114%;margin:0 4em"><a href="/wiki/Metabolism" title="Metabolism">Metabolism</a>: <a href="/wiki/Bioinorganic_chemistry" title="Bioinorganic chemistry">Metal metabolism</a></div></th></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Transition_metal" title="Transition metal">Transition metal</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Iron_metabolism" scope="row" class="navbox-group" style="width:1%"><a class="mw-selflink selflink">Iron metabolism</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Duodenum" title="Duodenum">Absorption in<br />duodenum</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Iron(II)_oxide" title="Iron(II) oxide">Iron(II) oxide</a>:</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/DMT1" class="mw-redirect" title="DMT1">DMT1 (SLC11A2)</a></li> <li><a href="/wiki/Ferritin" title="Ferritin">Ferritin</a></li> <li><a href="/wiki/Hephaestin" title="Hephaestin">Hephaestin</a>/<a href="/wiki/Ferroportin" title="Ferroportin">Ferroportin (SLC11A3/SLC40A1)</a></li> <li><a href="/wiki/Transferrin" title="Transferrin">Transferrin</a> to <a href="/wiki/Transferrin_receptor" title="Transferrin receptor">Transferrin receptor</a> <ul><li><a href="/wiki/Transferrin_receptor" title="Transferrin receptor">TFR1</a></li> <li><a href="/wiki/Transferrin_receptor" title="Transferrin receptor">TFR2</a></li></ul></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Iron(III)_oxide" title="Iron(III) oxide">Iron(III) oxide</a>:</th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Duodenal_cytochrome_B" title="Duodenal cytochrome B">Duodenal cytochrome B</a></li> <li><a href="/wiki/Integrin" title="Integrin">Integrin</a></li> <li><a href="/wiki/Calreticulin" title="Calreticulin">Calreticulin/mobilferrin</a></li> <li><a href="/wiki/Ferritin" title="Ferritin">Ferritin</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%">Other</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th id="Iron-binding_proteins:" scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Iron-binding_proteins" title="Iron-binding proteins">Iron-binding proteins</a>:</th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Ferritin" title="Ferritin">Ferritin</a></li></ul> </div></td></tr><tr><td colspan="2" class="navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Hepcidin" title="Hepcidin">Hepcidin</a>/<a href="/wiki/HAMP" class="mw-redirect" title="HAMP">HAMP</a></li> <li><a href="/wiki/Hemojuvelin" title="Hemojuvelin">Hemojuvelin</a></li> <li><a href="/wiki/Iron-responsive_element-binding_protein" title="Iron-responsive element-binding protein">Iron-responsive element-binding protein</a> <ul><li><a href="/wiki/Aconitase" title="Aconitase">Aconitase</a></li></ul></li> <li><a href="/wiki/Ceruloplasmin" title="Ceruloplasmin">Ceruloplasmin</a></li> <li><a href="/wiki/HFE_(gene)" title="HFE (gene)">HFE</a></li> <li><a href="/wiki/Hemosiderin" title="Hemosiderin">Hemosiderin</a></li> <li><a href="/wiki/Lactoferrin" title="Lactoferrin">Lactoferrin</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Copper_in_health" class="mw-redirect" title="Copper in health">Copper metabolism</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/ATP7A" title="ATP7A">ATP7A</a></li> <li><a href="/wiki/Wilson_disease_protein" title="Wilson disease protein">ATP7B</a></li> <li><a href="/wiki/Ceruloplasmin" title="Ceruloplasmin">Ceruloplasmin</a></li> <li><a href="/wiki/SLC31A1" class="mw-redirect" title="SLC31A1">SLC31A1</a></li> <li><a href="/wiki/ATOX1" title="ATOX1">ATOX1</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Zinc_metabolism" class="mw-redirect" title="Zinc metabolism">Zinc metabolism</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/TMC6" title="TMC6">TMC6</a></li> <li><a href="/wiki/TMC8" title="TMC8">TMC8</a></li> <li><a href="/wiki/SLC30A1" class="mw-redirect" title="SLC30A1">SLC30A1</a></li> <li><a href="/wiki/SLC39A4" class="mw-redirect" title="SLC39A4">SLC39A4</a></li></ul> </div></td></tr></tbody></table><div></div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Electrolyte" title="Electrolyte">Electrolyte</a></th><td class="navbox-list-with-group navbox-list navbox-odd hlist" style="width:100%;padding:0"><div style="padding:0 0.25em"></div><table class="nowraplinks navbox-subgroup" style="border-spacing:0"><tbody><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Sodium_metabolism" class="mw-redirect" title="Sodium metabolism">Sodium metabolism</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Na%2B/K%2B-ATPase" class="mw-redirect" title="Na+/K+-ATPase">Na<sup>+</sup>/K<sup>+</sup>-ATPase</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Phosphate_metabolism" class="mw-redirect" title="Phosphate metabolism">Phosphate metabolism</a></th><td class="navbox-list-with-group navbox-list navbox-even" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Phosphoric_acids_and_phosphates" title="Phosphoric acids and phosphates">Phosphoric acids and phosphates</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Magnesium_in_biology" title="Magnesium in biology">Magnesium metabolism</a></th><td class="navbox-list-with-group navbox-list navbox-odd" style="width:100%;padding:0"><div style="padding:0 0.25em"> <ul><li><a href="/wiki/Magnesium_transporter" title="Magnesium transporter">Magnesium transporter</a></li></ul> </div></td></tr><tr><th scope="row" class="navbox-group" style="width:1%"><a href="/wiki/Calcium_metabolism" title="Calcium metabolism">Calcium metabolism</a></th><td 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