Iron is an essential trace element required for growth and development of all lving organisms. 

Regulation of Iron (homeostasis)

Iron content is reuglated by controlling iron absorption, Iron recycling and release of iron from the cells in which it is stored.

Hepcidin: is an important regulator of iron homeostasis. High levels of human hepcidin result in reduced iron levels and vice vera. Mutations in the hepcidin gene which result in lack of hepcidin activity are associated with juvenile hemochromatosis, a severe iron overload disease. (Foltz, US12/990137)

Increasing evidence suggests that hepcidin is involved in iron sequestration during inflammation. Hepcidin gene expression has been observed to be robustly upregulated after inflammatory stimuli, such as infections. A strong correlation between hepcidin expression and anemia of inflammation was also found in patients with chronic inflammatory diseases, including bacterial, fungal and viral infections. (Foltz, US12/990137).

Human hepcidin is a 25 amino acid peptide. Its cDNA encodes a 83 amino acid pre-propeptide in mice and an 84 amino acid pre-propeptide in rat and human. The 24 residue N terminal signal peptide is first cleaved to produce pro-hepcidin, which is then further processed to produce mature hepcidin. (Foltz, US12/990137)

Ferritin is an iron storage protein that plays a key role in iron homeostasis and cellular antioxidant activity. The amino acid sequences of ferritins isolated from different species are very different; mammalian ferritins are mainly composed of structurally similar heavy (H)-chain (21 kDa) and light (L)-chain (19 kDa) subunits. (Du, “Potential of Ferritin-Based Platforms for Tumor Immunotherapy” Molecules, 27(9), 2022). 

Iron Absorption: Iron is absorbed predominantly in the duodenum and upper jejunum by enterocytes. A feeback mechaism exists that enhances iron absorption in individuals who are iron deficient and that reduces iron absorption in people with iron overload. (Andrews, Ann. Rev. Genomics Hum. Genet., 1: 75 (2000).

Iron Recylcing: 

Iron is recycled from degraded red cells by reticuloendothelial macrophages in bone marrow, hepatic Kupffer cells and spleen. 

Iron Release: 

–Ferroportin: Iron release is controlled by ferroportin, a major iron export protein located on the cell surface of enterocyctes, macrophages and hepatocytes, the main cells capable of releasing iron into plasma. Hepcidin binds to ferroportin and decreases its functional activity by causing it to be internalized form the cell surface and degraded. (Foltz, US12/990137)

Disorders of Iron Hoemeostasis

Common disorders of iron homeostasis include anemia, spesis, anemia of inflammation, anemia of cancer, chemotherpay induced anemia, chronic inflammatory anemia, congestive heart failure, end stage renal disorder, chronic kidney disease, iron deficiency anemia, ferroportin disease, diabetes, rheumatodi arthritis, arteriosclerosis, tumors, and red blood cell disorders. 

Treatment of Anemia/iron disorders

(Foltz, US12/990137) teaches methods of treating a human with elevated levels of hepcidin by adminstiering anti-hepcidin antibodies either alone or in combination with an erythropoiesis stimular such as erythropoietin. (see therapeutic applications of antibodies).