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