Molecular aspects of iron absorption and HFE expression Seppo Parkkila, Onni Niemelä, Robert S. Britton, Robert E. Fleming, Abdul Waheed, Bruce R. Bacon, William S. Sly  Gastroenterology  Volume 121, Issue 6, Pages 1489-1496 (December 2001) DOI: 10.1053/gast.2001.29617 Copyright © 2001 American Gastroenterological Association Terms and Conditions

Fig. 1 A schematic model of HFE regulation of iron transport in duodenal enterocytes. A and B correspond to villal and cryptal enterocytes, respectively. The enterocytes differentiate and become mature absorptive cells during migration from the crypts to the apex of the villus. Crypt cells express TfR and HFE, and the uptake of circulating transferrin (Tf)-bound iron may play an important role in regulating duodenal iron absorption. Tf-bound iron is endocytosed after binding to TfR at the basolateral cell surface. Acidification of the endosome causes iron to be released from Tf. Iron is then transported across the endosomal membrane and can enter the iron regulatory pool or bind to ferritin. The complex of apoTf and TfR is recycled back to the basolateral cell surface by exocytosis. Associated with TfR, HFE protein may enhance Tf-dependent iron uptake in crypt cells. C282Y mutant HFE may lack this facilitating effect on TfR-dependent iron uptake, thus decreasing the regulatory iron pool of the crypt cell. This would provide a signal in HH to preprogram the enterocytes to absorb more iron when they mature into villal enterocytes. Consistent with this hypothesis, increased expression of DMT1, an apical iron transporter, and ferroportin 1, a basolateral iron transporter, has been observed in the duodenum of HH patients.63,64 Gastroenterology 2001 121, 1489-1496DOI: (10.1053/gast.2001.29617) Copyright © 2001 American Gastroenterological Association Terms and Conditions