Regulation of iron absorption: proteins involved in duodenal mucosal uptake and transport.

Newly identified iron (Fe)-binding proteins isolated from both rat and human duodenal mucosa permit a better understanding of Fe absorption. Mucins bind Fe at acid pH to keep it soluble and available for absorption at the more alkaline pH of the duodenum; this explains the development of Fe deficiency in achlorhydric subjects. Integrin was identified on the surface of enterocytes in association with radioiron and is believed to facilitate the transfer of Fe through the microvillous membrane. Mobilferrin, a 56 kDa Fe-binding protein, was identified in enterocyte cytosol. It coprecipitates with integrin and appears in close association with integrin in the apical cytoplasm of absorptive cells. We postulate it accepts dietary Fe from integrin and acts as the shuttle protein from Fe in the cytoplasm. Since Fe in enterocytes remains in equilibrium with body stores, we postulate mucosal Fe uptake is regulated by the number of Fe-binding sites either occupied or unoccupied by Fe on mobilferrin. Fe repletion of enterocytes from body stores is probably accomplished via transferrin receptors on the basal membranes of enterocytes. Increased transfer of Fe from blood into absorptive enterocytes occurs in Fe-replete animals to inhibit mucosal uptake of dietary Fe. Little transfer of Fe from plasma to enterocytes occurs in Fe deficiency. Enhanced mucosal transfer into the body occurs with increased body need for Fe. The exact mechanism for mucosal transfer of Fe into the plasma has not been defined but may also be mediated by an integrin.(ABSTRACT TRUNCATED AT 250 WORDS)