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.
Publication types
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Comparative Study
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Bacterial Proteins / metabolism
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CHO Cells
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Carrier Proteins / metabolism
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Cloning, Molecular
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Cricetinae
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Duodenum / cytology
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Duodenum / metabolism*
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Epithelial Cells / metabolism
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HeLa Cells
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Heme / metabolism*
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Humans
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Hypoxia / metabolism
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Intestinal Absorption / physiology
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Iron / metabolism
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Iron Deficiencies
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / metabolism*
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Mice
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Molecular Sequence Data
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Oocytes / metabolism
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Proton-Coupled Folate Transporter
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Rabbits
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Rats
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Sequence Alignment
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Transferrin / metabolism
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Xenopus
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Zebrafish
Substances
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Bacterial Proteins
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Carrier Proteins
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Membrane Transport Proteins
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Proton-Coupled Folate Transporter
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RNA, Messenger
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SLC46A1 protein, human
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Tet O resistance protein, Bacteria
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Transferrin
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Heme
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Iron