Duodenal cytochrome B
Duodenal cytochrome B (Dcytb) also known as cytochrome b reductase 1 is an enzyme that in humans is encoded by the CYBRD1 gene.
CYBRD1 | |||||||||||||||||||||||||
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Aliases | CYBRD1, CYB561A2, DCYTB, FRRS3, cytochrome b reductase 1 | ||||||||||||||||||||||||
External IDs | OMIM: 605745 MGI: 2654575 HomoloGene: 69387 GeneCards: CYBRD1 | ||||||||||||||||||||||||
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Species | Human | Mouse | |||||||||||||||||||||||
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Location (UCSC) | Chr 2: 171.52 – 171.56 Mb | Chr 2: 71.12 – 71.14 Mb | |||||||||||||||||||||||
PubMed search | [3] | [4] | |||||||||||||||||||||||
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Dcytb CYBRD1 was first identified as a ferric reductase enzyme which catalyzes the reduction of Fe3+ to Fe2+ required for dietary iron absorption in the duodenum of mammals.[5] Dcytb mRNA and protein levels in the gut are increased by iron deficiency and hypoxia which acts to promote dietary iron absorption. The effect of iron deficiency and hypoxia on Dcytb levels are medicated via the HIF2 (Hypoxia inducible factor 2) transcription factor which binds to hypoxia response elements within the Dcytb promoter and increases transcription of the gene.[6] DCYTB protein has also been found in other tissues, such as lung epithelial cells[7] and in the plasma membrane of mature red blood cells of scorbutic species (unable to make ascorbate) such as human and guinea pig[8] but not in other species which have retained the ability to synthesise ascorbate like mice and rat. This has led to the notion that Dcytb may have an additional role in ascorbate metabolism in scorbutic species. DCYTB protein has also been found in breast tissue (epithelial and myoepithelial cells) and high DCYTB levels are associated with a favourable prognosis in patients with breast cancer.[9] A single nucleotide polymorphism (SNP) within the DCYTB promoter (SNP rs884409) which reduced functional DCYTB promoter activity was also associated with reduced serum ferrtin levels in a patient cohort with C282Y haemochromatosis.[10]
References
- GRCh38: Ensembl release 89: ENSG00000071967 - Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000027015 - Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- McKie AT, Barrow D, Latunde-Dada GO, Rolfs A, Sager G, Mudaly E, Mudaly M, Richardson C, Barlow D, Bomford A, Peters TJ, Raja KB, Shirali S, Hediger MA, Farzaneh F, Simpson RJ (March 2001). "An iron-regulated ferric reductase associated with the absorption of dietary iron". Science. 291 (5509): 1755–9. Bibcode:2001Sci...291.1755M. doi:10.1126/science.1057206. PMID 11230685. S2CID 44351106.
- Shah YM, Matsubara T, Ito S, Yim SH, Gonzalez FJ (February 2009). "Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency". Cell Metabolism. 9 (2): 152–64. doi:10.1016/j.cmet.2008.12.012. PMC 2659630. PMID 19147412.
- Turi JL, Wang X, McKie AT, Nozik-Grayck E, Mamo LB, Crissman K, Piantadosi CA, Ghio AJ (August 2006). "Duodenal cytochrome b: a novel ferrireductase in airway epithelial cells". American Journal of Physiology. Lung Cellular and Molecular Physiology. 291 (2): L272–80. doi:10.1152/ajplung.00342.2005. PMID 16510471.
- Su D, May JM, Koury MJ, Asard H (December 2006). "Human erythrocyte membranes contain a cytochrome b561 that may be involved in extracellular ascorbate recycling". The Journal of Biological Chemistry. 281 (52): 39852–9. doi:10.1074/jbc.M606543200. PMID 17068337.
- Lemler DJ, Lynch ML, Tesfay L, Deng Z, Paul BT, Wang X, Hegde P, Manz DH, Torti SV, Torti FM (March 2017). "DCYTB is a predictor of outcome in breast cancer that functions via iron-independent mechanisms". Breast Cancer Research. 19 (1): 25. doi:10.1186/s13058-017-0814-9. PMC 5341190. PMID 28270217.
- Constantine CC, Anderson GJ, Vulpe CD, McLaren CE, Bahlo M, Yeap HL, Gertig DM, Osborne NJ, Bertalli NA, Beckman KB, Chen V, Matak P, McKie AT, Delatycki MB, Olynyk JK, English DR, Southey MC, Giles GG, Hopper JL, Allen KJ, Gurrin LC (October 2009). "A novel association between a SNP in CYBRD1 and serum ferritin levels in a cohort study of HFE hereditary haemochromatosis". British Journal of Haematology. 147 (1): 140–9. doi:10.1111/j.1365-2141.2009.07843.x. PMC 2767327. PMID 19673882.
External links
- duodenal+cytochrome+b,+human at the US National Library of Medicine Medical Subject Headings (MeSH)