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

@article{Mckie2001AnIF,
  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},
  journal={Science},
  year={2001},
  volume={291},
  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.
TLDR
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.
TLDR
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.
TLDR
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
TLDR
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
TLDR
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
TLDR
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.
TLDR
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
TLDR
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.
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