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A Proton Pump Inhibitor a Day Keeps the Iron Away
Priya Handa, PhD, Kris V. Kowdley, MD Clinical Gastroenterology and Hepatology Volume 14, Issue 1, Pages (January 2016) DOI: /j.cgh Copyright © 2016 AGA Institute Terms and Conditions
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Figure 1 The role of PPIs in inhibiting iron absorption. Dietary nonheme (predominantly ferric or Fe3+) iron is thought to be transported by 2 main ways: Tf-bound or non–Tf-bound. Iron binds Tf, which in turn binds to the transferrin receptor on the cell surface (TfR1) via receptor-mediated endocytosis. Fe3+ is released from Tf as a result of the decrease in endosomal pH, and an endosomal ferrireductase, six-transmembrane epithelial antigen of the prostate 3 (STEAP3), reduces it to Fe2+. The Fe2+ iron then is transported through the endosomal divalent metal transporter (DMT1) into the cytosol. This iron becomes part of the labile iron pool, which can be stored as a complex with ferritin or used for synthesis of Fe-containing proteins or exported out of the cell by ferroportin (FPN1). Non–Tf-bound iron is taken up by ferrireductases such as duodenal cytochrome b (DCYTB). In the presence of a proton gradient, such enzymes reduce ferric to ferrous, which are transported by the DMT1 into the enterocyte. Because a low pH and protons are needed for both extracellular and endosomal ferrireductases, inhibiting proton pumps by PPIs diminishes the absorption of iron. Clinical Gastroenterology and Hepatology , DOI: ( /j.cgh ) Copyright © 2016 AGA Institute Terms and Conditions
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