[...]... incorporation of iron into transferrin (Tf) 12 Iron Metabolism Intestinal iron absorption is dependent on the body iron needs and is a tightly controlled process Recent studies indicate that this process is accomplished by modulating the expression levels of DMT1, DcytB and FPN by multiple pathways Iron regulatory proteins (IRPs) are essential for intestinal iron absorption DMT1 mRNA has an iron responsive... regulation of cellular iron homeostasis, its alterations in diseases and new research lines to be explored in the future 2 Cellular iron homeostasis Cellular iron maintenance involves the coordination of iron uptake, utilization, and storage to ensure appropriate levels of iron inside the cell Although transcriptional regulation of iron metabolism has been reported in the literature; cellular iron homeostasis... important iron regulatory hormones, predominantly secreted by liver hepatocytes Thus, intestinal iron absorption is coordinately regulated by several signaling pathways and is sensitive to hypoxia by HIF-2 , enterocyte iron levels by IRP/IRE and bodily iron levels by hepcidin Although iron uptake into the body is tightly controlled, iron loss does not appear to be regulated Under normal conditions iron. .. cells may employ additional means to promote iron export, such as upregulation of hephaestin in response to iron loading and/or the expression of alternative exporters or ferroxidases A major advance in the understanding of iron metabolism was the discovery of the iron regulatory hormone hepcidin nearly 10 years ago Hepcidin was originally identified as an Iron Metabolism in Humans: An Overview 15 antimicrobial... 65 mg of iron in healthy volunteers caused > 5-fold increase in hepcidin within 1 day [45] Hepcidin mRNA moves with the Fig 9 Schematic Diagram showing the regulation of circulating iron levels by Hepcidin 16 Iron Metabolism body's iron levels, increasing as they increase and decreasing as they decrease [46] Hepcidin regulates iron uptake constantly on a daily basis, to maintain sufficient iron stores... essential for iron absorption following iron deficiency Cell Metab 2009; 9: 152–64 20 Iron Metabolism [25] Mastrogiannaki M, Matak P, Keith B, Simon MC, Vaulont S, Peyssonnaux C HIF2alpha, but not HIF-1alpha, promotes iron absorption in mice J Clin Invest 2009; 119: 1159–66 [26] Sanchez M, Galy B, Muckenthaler MU, Hentze MW Iron- regulatory proteins limit hypoxia-inducible factor-2alpha expression in iron deficiency... K, Barrow D, et al A novel duodenal iron regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation Mol Cell 2000; 5: 299–309 [34] Abboud S, Haile DJ A novel mammalian iron- regulated protein involved in intracellular iron metabolism J Biol Chem 2000; 275: 19906–12 [35] Zhang AS, Xiong S, Tsukamoto H, Enns CA Localization of iron metabolism- related mRNAs in rat liver... contain iron Therefore, cells require iron to function properly However, mammals have no physiological excretion mechanisms to release an excess of iron and consequently, iron homeostasis must be tightly controlled on both the systemic and cellular levels to provide just the right amounts of iron at all times If an adequate balance of iron is not achieved, it will cause a clinical disorder Iron is... to 40 mg of iron, so women in their reproductive years need to absorb approximately 2 mg of iron per day However, when dietary iron is more abundant, absorption is appropriately attenuated Fig 7 Diagram showing the physiological turnover of iron in the body 5 Mechanisms regulating Iron absorption The iron stores in the body are regulated by intestinal absorption Intestinal absorption of iron is itself... repressor or Cellular Iron Metabolism – The IRP/IRE Regulatory Network 27 stabilizer proteins Particularly in iron metabolism, this system involves the so-called IRP/IRE regulatory network 2.1 The IRP/IRE regulatory network The Iron Regulatory Protein (IRP) / Iron- Responsive Element (IRE) regulatory network is a post-transcriptional gene expression regulation system that controls cellular iron homeostasis . Chapter 1 Iron Metabolism in Humans: An Overview 3 Sarika Arora and Raj Kumar Kapoor Section 2 Cellular Iron Metabolism 23 Chapter 2 Cellular Iron Metabolism. Iron 59 Chapter 3 Relationship Between Iron and Erythropoiesis 61 Nadia Maria Sposi Section 4 Iron Metabolism in Pathological States 87 Chapter 4 Iron