title: Duodenal cytochrome b (DCYTB) in iron metabolism: an update on function and regulation.
abstract: Iron and ascorbate are vital cellular constituents in mammalian systems. The bulk-requirement for iron is during erythropoiesis leading to the generation of hemoglobin-containing erythrocytes. Additionally; both iron and ascorbate are required as co-factors in numerous metabolic reactions. Iron homeostasis is controlled at the level of uptake; rather than excretion. Accumulating evidence strongly suggests that in addition to the known ability of dietary ascorbate to enhance non-heme iron absorption in the gut; ascorbate regulates iron homeostasis. The involvement of ascorbate in dietary iron absorption extends beyond the direct chemical reduction of non-heme iron by dietary ascorbate. Among other activities; intra-enterocyte ascorbate appears to be involved in the provision of electrons to a family of trans-membrane redox enzymes; namely those of the cytochrome b561 class. These hemoproteins oxidize a pool of ascorbate on one side of the membrane in order to reduce an electron acceptor (e.g., non-heme iron) on the opposite side of the membrane. One member of this family; duodenal cytochrome b (DCYTB); may play an important role in ascorbate-dependent reduction of non-heme iron in the gut prior to uptake by ferrous-iron transporters. This review discusses the emerging relationship between cellular iron homeostasis; the emergent "IRP1-HIF2α axis"; DCYTB and ascorbate in relation to iron metabolism.
authors.affiliation: Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia. darius.lane@sydney.edu.au.
authors.forename: Darius J R
authors.initials: DJ
authors.lastname: Lane
authors.affiliation: Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia. dbae5413@uni.sydney.edu.au.
authors.forename: Dong-Hun
authors.initials: DH
authors.lastname: Bae
authors.affiliation: Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia. angelica.merlot@sydney.edu.au.
authors.forename: Angelica M
authors.initials: AM
authors.lastname: Merlot
authors.affiliation: Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia. sumit.sahni@sydney.edu.au.
authors.forename: Sumit
authors.initials: S
authors.lastname: Sahni
authors.affiliation: Molecular Pharmacology and Pathology Program, Department of Pathology and Bosch Institute, University of Sydney, Sydney, NSW 2006, Australia. d.richardson@sydney.edu.au.
authors.forename: Des R
authors.initials: DR
authors.lastname: Richardson
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D003573:Cytochrome b Group / Q000378:metabolism; D045303:Cytochromes b / Q000378:metabolism*; D004195:Disease Models, Animal; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D004920:Erythropoiesis / Q000187:drug effects; D006801:Humans; D035941:Iron Regulatory Protein 1 / Q000235:genetics / Q000378:metabolism; D019266:Iron, Dietary / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D001205:Ascorbic Acid; D051792:Basic Helix-Loop-Helix Proteins; D003573:Cytochrome b Group; D045303:Cytochromes b; D035941:Iron Regulatory Protein 1; D019266:Iron, Dietary; D000099162:Endothelial PAS Domain-Containing Protein 1; C023646:cytochrome b561; C546175:ACO1 protein, human
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