Intestinal Iron Transport and its Regulation

In recent years, a number of components of the iron absorption pathway have been identified, greatly increasing our understanding of this important process. These include two molecules involved in brush border iron uptake, the ferric reductase DcytB and the iron transporter DMT1, and two mediating iron transfer to the body, the iron transporter Ireg1 and the ferroxidase hephaestin (Hp). Analysis of the regulation of these molecules has provided us with valuable insights into how the body responds to changes in iron requirements, and has enabled us to re-examine how iron absorption is controlled, and in particular the mucosal block phenomenon. Evidence suggests that the block to absorption that follows a priming dose of iron is the result of elevated intracellular iron levels decreasing the expression of the brush border iron transporter DMT1. Based on these observations, it is possible to propose a general model for the regulation of iron absorption whereby the basolateral transfer step involving Ireg1 and Hp controls the rate of absorption. In this model, DMT1 expression, and hence, brush border uptake, is regulated by local iron levels that are, in turn, determined by the rate of basolateral transfer.