Regulation of Intestinal Iron Absorption: Balancing Supply and Demand: Regulation of Intestinal Iron Absorption

Shazia Yaseen; Rai Hamza Akram; Basit Ali; Komal Zaheer; Memoona Rafique; Pakeeza Eman; Namal Fatima; Fazeelat Kausar; Muhammad Luqman

doi:10.54393/fbt.v4i03.149

Authors

Shazia Yaseen Department of Zoology, University of Okara, Okara, Pakistan
Rai Hamza Akram Services Institute of Medical Sciences, Lahore, Pakistan
Basit Ali Department of Chemical Engineering, University of Engineering and Technology, Peshawar, Pakistan
Komal Zaheer University Medical and Dental College, Faisalabad, Pakistan
Memoona Rafique Department of Optometry, Superior University, Lahore, Pakistan
Pakeeza Eman Department of Zoology, University of Okara, Okara, Pakistan
Namal Fatima Ameer-ud-Din Medical College, Lahore, Pakistan
Fazeelat Kausar Department of Molecular Biology, University of Okara, Okara, Pakistan
Muhammad Luqman Department of Microbiology, School of Life Sciences, Nanjing Normal University, Nanjing, China

DOI:

https://doi.org/10.54393/fbt.v4i03.149

Keywords:

Intestinal Iron, Ferroportin, Enterocytes, Hypoxia-Inducible Factor 2 (HIF-2), Ferritin, anemia

Abstract

Iron, an essential micronutrient, is involved in several physiological activities, including oxygen transport, cellular respiration, and DNA synthesis. Its homeostasis is strictly controlled to avoid overload and deficiency. Ferrous iron is taken up by intestinal enterocytes through the apical membrane with the help of divalent metal transporter 1 (DMT1). Iron can then be discharged into the bloodstream by ferroportin 1 (FPN1) or stored intracellularly in ferritin. Hepcidin, a hormone produced in the liver, binds to FPN1 and causes its internalization and degradation, a key factor in controlling systemic iron levels. Thus, hepcidin limits the absorption and release of iron by decreasing the iron outflow from enterocytes and macrophages. Iron-responsive element/iron regulatory protein (IRE/IRP) system and hypoxia-inducible factor 2 (HIF-2) are important cellular regulators of iron homeostasis. The IRE/IRP system post-transcriptionally regulates the expression of iron-related proteins in response to iron availability. At the same time, HIF-2 promotes the expression of iron transporters and metabolic enzymes under hypoxic conditions. Iron-related disorders can result from disruptions in these regulatory mechanisms; for instance, mutations in the genes encoding hepcidin, FPN1, or hereditary hemochromatosis protein (HFE) can cause iron overload disorders like hemochromatosis, while iron deficiency anemia is caused by impaired iron absorption due to genetic defects or nutritional deficiencies. A deeper understanding of these intricate mechanisms is crucial for developing effective strategies to prevent and treat iron-related disorders.

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