Mechanistic and regulatory aspects of intestinal iron absorption.

Abstract

Iron is an essential trace mineral that plays a number of important physiological roles in humans, including oxygen transport, energy metabolism, and neurotransmitter synthesis. Iron absorption by the proximal small bowel is a critical checkpoint in the maintenance of whole-body iron levels since, unlike most other essential nutrients, no regulated excretory systems exist for iron in humans. Maintaining proper iron levels is critical to avoid the adverse physiological consequences of either low or high tissue iron concentrations, as commonly occurs in iron-deficiency anemia and hereditary hemochromatosis, respectively. Exquisite regulatory mechanisms have thus evolved to modulate how much iron is acquired from the diet. Systemic sensing of iron levels is accomplished by a network of molecules that regulate transcription of the HAMP gene in hepatocytes, thus modulating levels of the serum-borne, iron-regulatory hormone hepcidin. Hepcidin decreases intestinal iron absorption by binding to the iron exporter ferroportin 1 on the basolateral surface of duodenal enterocytes, causing its internalization and degradation. Mucosal regulation of iron transport also occurs during low-iron states, via transcriptional (by hypoxia-inducible factor 2α) and posttranscriptional (by the iron-sensing iron-regulatory protein/iron-responsive element system) mechanisms. Recent studies demonstrated that these regulatory loops function in tandem to control expression or activity of key modulators of iron homeostasis. In health, body iron levels are maintained at appropriate levels; however, in several inherited disorders and in other pathophysiological states, iron sensing is perturbed and intestinal iron absorption is dysregulated. The iron-related phenotypes of these diseases exemplify the necessity of precisely regulating iron absorption to meet body demands.

• Authors: Sukru Gulec, Gregory J Anderson, James F Collins
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 307 Issue 4 Pg. G397-409 (Aug 15 2014) ISSN: 1522-1547 [Electronic] United States
• PMID: 24994858 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2014 the American Physiological Society.

Chemical References

• Cation Transport Proteins
• Ferric Compounds
• Hepcidins
• metal transporting protein 1
• solute carrier family 11- (proton-coupled divalent metal ion transporters), member 2
• Heme
• Cytochromes b
• Iron

Topics

• Anemia, Iron-Deficiency (physiopathology)
• Animals
• Biological Availability
• Cation Transport Proteins (genetics, metabolism)
• Cytochromes b (metabolism)
• Diet
• Enterocytes (metabolism)
• Ferric Compounds (metabolism)
• Heme (metabolism)
• Hemochromatosis (physiopathology)
• Hepatocytes (metabolism)
• Hepcidins (physiology)
• Homeostasis (physiology)
• Humans
• Intestinal Absorption (physiology)
• Iron (metabolism)
• Microvilli (metabolism)