Duodenal Cytochrome b (DCYTB) in Iron Metabolism: An Update on Function and Regulation

• Main Authors: Darius J. R. Lane, Dong-Hun Bae, Angelica M. Merlot, Sumit Sahni, Des R. Richardson
• Format: Article
• Language: English
• Published: MDPI AG 2015-03-01
• Series: Nutrients
• Subjects: DCYTB; CYBRD1; vitamin C; cytochrome b561; iron homeostasis; anemia; mouse model; HIF2α; IRP1
• Online Access: http://www.mdpi.com/2072-6643/7/4/2274

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.