Identification of an intestinal heme transporter.
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.
Shayeghi
Majid
M
Department of Life Sciences, Nutritional Sciences Research Division, Franklin-Wilkins Building, Kings College London, 150 Stamford Street, London SE1 9NN, UK.
Latunde-Dada
Gladys O
GO
Oakhill
Jonathan S
JS
Laftah
Abas H
AH
Takeuchi
Ken
K
Halliday
Neil
N
Khan
Yasmin
Y
Warley
Alice
A
McCann
Fiona E
FE
Hider
Robert C
RC
Frazer
David M
DM
Anderson
Gregory J
GJ
Vulpe
Christopher D
CD
Simpson
Robert J
RJ
McKie
Andrew T
AT
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
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