title: Identification of an intestinal heme transporter.
abstract: Dietary heme iron is an important nutritional source of iron in carnivores and omnivores that is more readily absorbed than non-heme iron derived from vegetables and grain. Most heme is absorbed in the proximal intestine, with absorptive capacity decreasing distally. We utilized a subtractive hybridization approach to isolate a heme transporter from duodenum by taking advantage of the intestinal gradient for heme absorption. Here we show a membrane protein named HCP 1 (heme carrier protein 1), with homology to bacterial metal-tetracycline transporters, mediates heme uptake by cells in a temperature-dependent and saturable manner. HCP 1 mRNA was highly expressed in duodenum and regulated by hypoxia. HCP 1 protein was iron regulated and localized to the brush-border membrane of duodenal enterocytes in iron deficiency. Our data indicate that HCP 1 is the long-sought intestinal heme transporter.
authors.affiliation: Department of Life Sciences, Nutritional Sciences Research Division, Franklin-Wilkins Building, Kings College London, 150 Stamford Street, London SE1 9NN, UK.
authors.forename: Majid
authors.initials: M
authors.lastname: Shayeghi
authors.forename: Gladys O
authors.initials: GO
authors.lastname: Latunde-Dada
authors.forename: Jonathan S
authors.initials: JS
authors.lastname: Oakhill
authors.forename: Abas H
authors.initials: AH
authors.lastname: Laftah
authors.forename: Ken
authors.initials: K
authors.lastname: Takeuchi
authors.forename: Neil
authors.initials: N
authors.lastname: Halliday
authors.forename: Yasmin
authors.initials: Y
authors.lastname: Khan
authors.forename: Alice
authors.initials: A
authors.lastname: Warley
authors.forename: Fiona E
authors.initials: FE
authors.lastname: McCann
authors.forename: Robert C
authors.initials: RC
authors.lastname: Hider
authors.forename: David M
authors.initials: DM
authors.lastname: Frazer
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Anderson
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Vulpe
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Simpson
authors.forename: Andrew T
authors.initials: AT
authors.lastname: McKie
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001426:Bacterial Proteins / Q000378:metabolism; D016466:CHO Cells; D002352:Carrier Proteins / Q000378:metabolism; D003001:Cloning, Molecular; D006224:Cricetinae; D004386:Duodenum / Q000166:cytology / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism; D006367:HeLa Cells; D006418:Heme / Q000378:metabolism*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D007408:Intestinal Absorption / Q000502:physiology; D007501:Iron / Q000378:metabolism; D000090463:Iron Deficiencies; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000378:metabolism; D058979:Proton-Coupled Folate Transporter; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D016415:Sequence Alignment; D014168:Transferrin / Q000378:metabolism; D014981:Xenopus; D015027:Zebrafish
chemical_list: D001426:Bacterial Proteins; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D058979:Proton-Coupled Folate Transporter; D012333:RNA, Messenger; C505058:SLC46A1 protein, human; C083139:Tet O resistance protein, Bacteria; D014168:Transferrin; D006418:Heme; D007501:Iron