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Cited by 688Iron Metabolism and DisordersNeurological diseases and metabolismTrace Elements in Health

Current understanding of iron homeostasis

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Anderson, Gregory J, Frazer, David M·2017·The American Journal of Clinical Nutrition
DOI 10.3945/ajcn.117.155804PMC PMC5701707
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Abstract

Iron is an essential trace element, but it is also toxic in excess, and thus mammals have developed elegant mechanisms for keeping both cellular and whole-body iron concentrations within the optimal physiologic range. In the diet, iron is either sequestered within heme or in various nonheme forms. Although the absorption of heme iron is poorly understood, nonheme iron is transported across the apical membrane of the intestinal enterocyte by divalent metal-ion transporter 1 (DMT1) and is exported into the circulation via ferroportin 1 (FPN1). Newly absorbed iron binds to plasma transferrin and is distributed around the body to sites of utilization with the erythroid marrow having particularly high iron requirements. Iron-loaded transferrin binds to transferrin receptor 1 on the surface of most body cells, and after endocytosis of the complex, iron enters the cytoplasm via DMT1 in the endosomal membrane. This iron can be used for metabolic functions, stored within cytosolic ferritin, or exported from the cell via FPN1. Cellular iron concentrations are modulated by the iron regulatory proteins (IRPs) IRP1 and IRP2. At the whole-body level, dietary iron absorption and iron export from the tissues into the plasma are regulated by the liver-derived peptide hepcidin. When tissue iron demands are high, hepcidin concentrations are low and vice versa. Too little or too much iron can have important clinical consequences. Most iron deficiency reflects an inadequate supply of iron in the diet, whereas iron excess is usually associated with hereditary disorders. These disorders include various forms of hemochromatosis, which are characterized by inadequate hepcidin production and, thus, increased dietary iron intake, and iron-loading anemias whereby both increased iron absorption and transfusion therapy contribute to the iron overload. Despite major recent advances, much remains to be learned about iron physiology and pathophysiology.

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  • In other cells throughout the body, divalent metal transporter 1, divalent cation transporter 1, or other carrier-mediated systems play an important role in moving Fe2+, Zn2+, and Cu2+ across the membrane.

    “In other cells throughout the body divalent metal transporter 1, divalent cation transporter 1, or other carrier-mediated systems play an important role in moving Fe2+, Zn2+, and Cu2+ across the membrane”

    From Physiological mechanisms determining eccrine sweat composition (2020) · cites this paper as Anderson and Frazer 2017

    The Systemic iron transport and its delivery to tissues section says that iron moves across the endosomal membrane into cells via DMT1, and the Intestinal iron absorption section identifies ferrous iron (Fe2+) as a DMT1 substrate. The cited passages do not establish the claim that these systems move Zn2+ or Cu2+ across membranes in other body cells. (LLM, conf=0.86)

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Research works printed but not linked: 38

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Cited by

Sorted by citations

Authors
Anderson, G. J., & Frazer, D. M.
Affiliations
  • The University of Queensland (AU)
  • QIMR Berghofer Medical Research Institute (AU)
Corresponding author
Anderson, Gregory J
ORCID
Venue
The American Journal of Clinical Nutrition
Publisher
Elsevier BV
Published
2017-12
Volume
106
Issue
Suppl 6
Pages
1559S-1566S
ISSN
0002-9165 (ISSN-L)
DOI
10.3945/ajcn.117.155804
PMC
PMC5701707
OpenAlex
W2767127256
Cited by
688
References
15
Citations by year
2026: 80 · 2025: 90 · 2024: 98 · 2023: 100 · 2022: 84 · 2021: 93 · 2020: 81 · 2019: 39 · 2018: 18 · 2017: 5
FWCI
6.17
Type
journal article
Language
en
Open access
Licence
Locations
  • American Journal of Clinical Nutrition (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
  • Life Sciences › Neuroscience › Neurology › Neurological diseases and metabolism
  • Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords
iron homeostasis, iron absorption, heme iron, non-heme iron, DMT1, ferroportin 1, transferrin, transferrin receptor 1, ferritin, iron regulatory proteins, hepcidin, iron deficiency, iron overload, hemochromatosis
MeSH terms
Iron Deficiencies, Ferroportin, Solute Carrier Family 11, Member 2, Ferritins, Hemochromatosis, Homeostasis, Humans, Intestinal Absorption, Iron, Receptors, Transferrin, Transferrin, Anemia, Iron-Deficiency, Iron Overload, Enterocytes, Cation Transport Proteins, Iron Regulatory Protein 1, Iron Regulatory Protein 2, Hepcidins

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