The role of duodenal cytochrome b in intestinal iron absorption remains unclear

Frazer, David M.; Wilkins, Sarah J.; Vulpe, Chris D.; Anderson, Gregory J.

doi:10.1182/blood-2005-07-2923

Cited by 19 publications

(13 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This activity is generally thought to be mediated by the ferrireductase duodenal cytochrome B (DCYTB 2 ; CYBRD1) located at the apical membrane of enterocytes (14). Consistent with this possibility is the observation that Dcytb mRNA expression is markedly up-regulated in iron-deficient mouse intestines (14,15). Cybrd1-null mice, however, show no apparent defects in iron metabolism even in the context of iron deficiency, suggesting that DCYTB can be dispensable for iron absorption (16).…”

Section: Dietary Iron Absorption By the Enterocytementioning

confidence: 95%

Iron transport proteins: Gateways of cellular and systemic iron homeostasis

Knutson

2017

Journal of Biological Chemistry

117

View full text Add to dashboard Cite

Edited by F. Peter GuengerichCellular iron homeostasis is maintained by iron and heme transport proteins that work in concert with ferrireductases, ferroxidases, and chaperones to direct the movement of iron into, within, and out of cells. Systemic iron homeostasis is regulated by the liver-derived peptide hormone, hepcidin. The interface between cellular and systemic iron homeostasis is readily observed in the highly dynamic iron handling of four main cell types: duodenal enterocytes, erythrocyte precursors, macrophages, and hepatocytes. This review provides an overview of how these cell types handle iron, highlighting how iron and heme transporters mediate the exchange and distribution of body iron in health and disease.

show abstract

Section: Dietary Iron Absorption By the Enterocytementioning

confidence: 95%

Iron transport proteins: Gateways of cellular and systemic iron homeostasis

Knutson

2017

Journal of Biological Chemistry

117

View full text Add to dashboard Cite

show abstract

“…The iron regulated ferric reductase, duodenal cytochrome B (Dcytb) is predicted to be involved in this process [11] but its role has yet to be fully defined. Mice in which the gene encoding Dcytb has been deleted do not show disturbed systemic iron homeostasis [12], but the animals were not studied under conditions where the role of Dcytb in iron absorption could be evaluated definitively [13]. Ferrous iron is transported across the brush border membrane into the enterocyte via the ferrous iron transporter DMT1 [1,8].…”

Section: Iron Homeostasis In the Bodymentioning

confidence: 99%

Mechanisms of iron loading and toxicity

Anderson

2007

Am. J. Hematol.

Self Cite

117

View full text Add to dashboard Cite

Normal iron homeostasis is a finely balanced system that reflects iron absorption, loss and utilization. The body has no mechanism for the active excretion of iron, so body iron levels are controlled at the point of absorption in the small intestine. Disturbances in this equilibrium, such as those leading to enhanced absorption, can have significant clinical consequences. Continued excessive iron uptake is followed by iron deposition in various tissues, ultimately leading to tissue damage, and possibly end‐organ failure. In this review, current concepts in normal iron homeostasis, and iron loading are explained. The clinical consequences as well as the differences between primary and secondary iron loading are also reviewed, and some future research priorities are discussed. Am. J. Hematol., 2007. © 2007 Wiley‐Liss, Inc.

show abstract

“…However, Gunshin et al recently reported that knockout of Dcytb had little or no impact on body iron stores, even in animals with low iron diet. This indicates that the role of Dcytb is far from clear [9,10].…”

Section: Introductionmentioning

confidence: 99%

An ascorbate-reducible cytochrome b561 is localized in macrophage lysosomes

Zhang

Bérczi

et al. 2006

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

Cytochromes b561 (Cyts b561) are a family of intrinsic membrane proteins involved in ascorbate-mediated transmembrane electron transport. The chromaffin granule Cyt b561 (CGCytb) is believed to transport electrons donated by extravesicular ascorbate (ASC) across the membrane to intravesicular monodehydroascorbate (MDA) supporting catecholamine synthesis in neuroendocrine tissues. Another isoform, the duodenal Cyt b561 (Dcytb), was reported to have ferric reductase activity, possibly facilitating intestinal iron uptake. Herein, a new Cyt b561 homologue, LCytb (for lysosomal Cytb561) was found expressed in the late endosomal-lysosomal membrane. LCytb shared high sequence similarity with CGCytb (45% identity) and Dcytb (42% identity). Moreover, four heme-coordinating His residues, and putative ASC and MDA binding sites were highly conserved. Recombinant LCytb exhibited an ASC-reducible b-type Cyt absorbance spectrum with α-band maximum at 561 nm in the spectrum of the reduced protein. Northern blots and Western blots revealed that LCytb was predominantly expressed in lung, spleen, thymus, testis and placenta. In situ hybridization and immunofluorescence studies further demonstrated that the protein was expressed in the alveolar macrophages of the lung, in the white pulp of the spleen, widespread in the thymus, and in the Sertoli cells of the testis. Sequence analysis indicated the presence of a (DE)XXXL(LI)-type signal in the C-terminal of the protein, predicting a late endosomal-lysosomal subcellular localization. This localization was confirmed by double labeling experiments in RAW264.7 and 293 cells, stably transfected with LCytb.

show abstract

The role of duodenal cytochrome b in intestinal iron absorption remains unclear

Cited by 19 publications

References 5 publications

Iron transport proteins: Gateways of cellular and systemic iron homeostasis

Iron transport proteins: Gateways of cellular and systemic iron homeostasis

Mechanisms of iron loading and toxicity

An ascorbate-reducible cytochrome b561 is localized in macrophage lysosomes

Contact Info

Product

Resources

About