An Iron-Regulated Ferric Reductase Associated with the Absorption of Dietary Iron

  title={An Iron-Regulated Ferric Reductase Associated with the Absorption of Dietary Iron},
  author={Andrew T. Mckie and Dalna Barrow and Gladys Oluyemisi Latunde-Dada and Andreas Rolfs and Giamal Sager and Elida Mudaly and Melitta Mudaly and Christopher Richardson and David J Barlow and Adrian Bomford and Timothy J. Peters and Kishor B. Raja and Sima Shirali and Matthias A. Hediger and Farzin Farzaneh and Robert J. Simpson},
  pages={1755 - 1759}
The ability of intestinal mucosa to absorb dietary ferric iron is attributed to the presence of a brush-border membrane reductase activity that displays adaptive responses to iron status. We have isolated a complementary DNA, Dcytb (for duodenal cytochrome b), which encoded a putative plasma membrane di-heme protein in mouse duodenal mucosa. Dcytb shared between 45 and 50% similarity to the cytochrome b561 family of plasma membrane reductases, was highly expressed in the brush-border membrane… 
Molecular and functional roles of duodenal cytochrome B (Dcytb) in iron metabolism.
Dcytb expression and function were modulated by iron and DMT1, both predominantly localised in the apical region of the duodenum were up-regulated in iron deficiency.
The role of duodenal cytochrome b in intestinal iron absorption remains unclear.
It is concluded that Dcytb is not necessary for dietary iron absorption in mice, but this conclusion should be interpreted with caution, as no direct measurements of iron absorption were made and the reliance on liver iron levels does not provide unequivocal evidence for or against an absorption defect.
Identification of an Intestinal Heme Transporter
Duodenal cytochrome B expression stimulates iron uptake by human intestinal epithelial cells.
Dcytb can act as a ferric reductase that stimulates iron uptake in Caco-2 cells, a human cell line model often used to mimic intestinal enterocytes.
The role of Dcytb in iron metabolism: an update.
  • A. Mckie
  • Biology
    Biochemical Society transactions
  • 2008
It is revealed that Dcytb is the only iron-regulated ferric reductase in the duodenal mucosa and that loss of D Cytb affects iron absorption, and ascorbate is the likely intracelluar electron donor.
Duodenal mucosal and plasma ascorbate levels of patients with iron deficiency
Examination of mucosal and plasma levels of ascorbate and dehydroascorbate in normal subjects and patients with iron deficiency that is known to be a stimulator for iron absorption support an important intracellular role of asCorbic acid in human dietary iron absorption.
Duodenal Cytochrome b (DCYTB) in Iron Metabolism: An Update on Function and Regulation
The emerging relationship between cellular iron homeostasis, the emergent “IRP1-HIF2α axis”, duodenal cytochrome b (DCYTB) and ascorbate in relation to iron metabolism are discussed.
Structural basis for promotion of duodenal iron absorption by enteric ferric reductase with ascorbate
Dietary iron absorption is regulated by duodenal cytochrome b (Dcytb), an integral membrane protein that catalyzes reduction of nonheme Fe3+ by electron transfer from ascorbate across the membrane.
Cybrd1 (duodenal cytochrome b) is not necessary for dietary iron absorption in mice.
It is found that loss of Cybrd1 had little or no impact on body iron stores, even in the setting of iron deficiency, which means that other mechanisms must be available for the reduction of dietary iron.
Recent advances in intestinal iron transport
The expression of hepcidin in turn is influenced by plasma transferrin saturation via a pathway that involves HFE, TfR2, and hemojuvelin, and future studies investigating how these molecules interact will provide a comprehensive understanding of this essential physiologic process.


Localisation of divalent metal transporter 1 (DMT1) to the microvillus membrane of rat duodenal enterocytes in iron deficiency, but to hepatocytes in iron overload
Results are consistent with a role for DMT1 in the transmembrane transport of non-transferrin bound iron from the intestinal lumen and from the portal blood.
Two distinctly regulated genes are required for ferric reduction, the first step of iron uptake in Saccharomyces cerevisiae
FRE2, a gene which is shown to account, together with FRE1, for the total membrane-associated ferric reductase activity of the cell, is cloned and molecularly characterized.
A ferric-chelate reductase for iron uptake from soils
The isolation of FRO2 has implications for the generation of crops with improved nutritional quality and increased growth in iron-deficient soils and for the treatment of iron deficiency in plants.
Ferric reductase of Saccharomyces cerevisiae: molecular characterization, role in iron uptake, and transcriptional control by iron.
The deduced amino acid sequence of the FRE1 protein exhibits hydrophobic regions compatible with transmembrane domains and has significant similarity to the sequence of a critical component of a human phagocyte oxidoreductase, suggesting that FRE1 is a structural component of the yeast ferric reductase.
Iron absorption by hypotransferrinaemic mice
In vivo mucosal uptake and carcass transfer of radioiron showed an inverse correlation with liver non‐haem iron content in homozygous hypotransferrinaemic mice, suggesting that some degree of control of absorption, albeit at markedly reduced sensitivity, can operate in these mice.
Cloning and characterization of a mammalian proton-coupled metal-ion transporter
A new metal-ion transporter in the rat, DCT1, which has an unusually broad substrate range that includes Fe2+, Zn2+, Mn2+, Co2+, Cd2+, Cu2+, Ni2+ and Pb2+.
Dietary iron levels and hypoxia independently affect iron absorption in mice.
The data suggest that the control of iron absorption by tissue oxygen acts through a mechanism independent of the control exerted by dietary or mucosal iron levels.