Identification of an intestinal heme transporter

Cell. 2005 Sep 9;122(5):789-801. doi: 10.1016/j.cell.2005.06.025.

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 / deficiency
  • Iron / metabolism
  • 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