Absorption of Iron from Ferritin Is Independent of Heme Iron and Ferrous Salts in Women and Rat Intestinal Segments.

Abstract

Ferritin iron from food is readily bioavailable to humans and has the potential for treating iron deficiency. Whether ferritin iron absorption is mechanistically different from iron absorption from small iron complexes/salts remains controversial. Here, we studied iron absorption (RBC 59 Fe) from radiolabeled ferritin iron (0.5 mg) in healthy women with or without nonferritin iron competitors, ferrous sulfate, or hemoglobin. A 9-fold excess of non-ferritin iron competitor had no significant effect on ferritin iron absorption. Larger amounts of iron (50 mg and a 99-fold excess of either competitor) inhibited iron absorption. To measure transport rates of iron that was absorbed inside ferritin, rat intestinal segments ex vivo were perfused with radiolabeled ferritin and compared to perfusion with ferric nitrilotriacetic (Fe-NTA), a well-studied form of chelated iron. Intestinal transport of iron absorbed inside exogenous ferritin was 14.8% of the rate measured for iron absorbed from chelated iron. In the steady state, endogenous enterocyte ferritin contained .90% of the iron absorbed from Fe-NTA or ferritin. We found that ferritin is a slow release source of iron, readily available to humans or animals, based on RBC iron incorporation. Ferritin iron is absorbed by a different mechanism than iron salts/chelates or heme iron. Recognition of a second, nonheme iron absorption process, ferritin endocytosis, emphasizes the need for more mechanistic studies on ferritin iron absorption and highlights the potential of ferritin present in foods such as legumes to contribute to solutions for global iron deficiency.

Linking iron-deficiency with allergy: role of molecular allergens and the microbiome

“…28,29 Ironcarrying proteins like ferritin from food are efficiently absorbed without depending on reduction or the heme transporter via receptor-mediated, clathrin-dependent endocytosis. 30 Absorption and increased iron accumulation were also found in the liver, when Fe(II) was ingested with glycine and asparagine, but not with other amino acids. 31 Once in the cell, iron is exported by ferroportin 1, also known as IREG1, MTP1, SLC40A1, FPN1, and HFE4, into the circulation.…”

Systemic Iron Homeostasis

“…The acid environment of the stomach and exposure to digestive enzymes cause a partial release of these iron forms from the digestate. Heme and non-heme iron appear to be absorbed by separate mechanisms (266), and there may be yet another pathway involved in ferritin absorption (241). Despite the importance of heme and ferritin as dietary sources of iron, and despite some promising leads (196,222,241), little is known about their transport and metabolism in the enterocyte.…”

“…Duodenal iron absorption requires that iron cross the apical membrane, followed by variable storage in cytoplasmic ferritin, then iron transport across the enterocyte and the transfer of iron across the basolateral membrane. Much evidence, especially the consequences of genetic disorders and mouse mutations that disable basolateral iron export, indicates that iron from ferritin or heme exits the enterocyte by the same route, i.e., that iron of heme and ferritin must be liberated in the absorptive endosome or in the cytoplasm (241,266). Thus no matter how it is taken up by the enterocyte, iron in its ferric form is delivered to plasma transferrin near the basolateral surface.…”

Overview of iron metabolism in health and disease

“…12 Although the mechanisms for uptake of dietary heme and ferritin are less well understood, evidence suggests that iron is subsequently liberated and enters a common pathway as inorganic iron in the enterocyte. 13,14 Iron taken up by enterocytes can be used directly for intrinsic cellular metabolic processes, stored, or exported across the basolateral membrane for systemic delivery. Iron is stored in enterocytes, like other cells, largely in the form of ferritin, which is comprised of a spherical nanocage of heavy (H) and light (L) chains surrounding a core of iron that is oxidized by H-ferritin.…”