Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Biochem Biophys Res Commun
2010 Mar 12;3933:471-5. doi: 10.1016/j.bbrc.2010.02.025.
Show Gene links
Show Anatomy links
Interaction of calcium with the human divalent metal-ion transporter-1.
Shawki A, Mackenzie B.
???displayArticle.abstract???
Iron deficiency is the most prevalent micronutrient deficiency worldwide. Whereas dietary calcium is known to reduce the bioavailability of iron, the molecular basis of this interaction is not understood. We tested the hypothesis that divalent metal-ion transporter-1 (DMT1)-the principal or only mechanism by which nonheme iron is taken up at the intestinal brush border-is shared also by calcium. We expressed human DMT1 in RNA-injected Xenopus oocytes and examined its activity using radiotracer assays and the voltage clamp. DMT1 did not mediate 45Ca2+ uptake. Instead, we found that Ca2+ blocked the Fe2+-evoked currents and inhibited 55Fe2+ uptake in a noncompetitive manner (K(i) approximately 20 mM). The mechanism of inhibition was independent of voltage and did not involve intracellular Ca2+ signaling. The alkaline-earth metal ions Ba2+, Sr2+, and Mg2+ also inhibited DMT1-mediated iron-transport activity. We conclude that Ca2+ is a low-affinity noncompetitive inhibitor--but not a transported substrate--of DMT1, explaining in part the effect of high dietary calcium on iron bioavailability.
Barton,
Calcium inhibition of inorganic iron absorption in rats.
1983, Pubmed
Barton,
Calcium inhibition of inorganic iron absorption in rats.
1983,
Pubmed Benkhedda,
Effect of calcium on iron absorption in women with marginal iron status.
2010,
Pubmed Ci,
Intracellular Ca(2+) regulates the cellular iron uptake in K562 cells.
2003,
Pubmed Fleming,
Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene.
1997,
Pubmed Fleming,
Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport.
1998,
Pubmed Garrick,
DMT1: a mammalian transporter for multiple metals.
2003,
Pubmed Gleerup,
Iron absorption from the whole diet: comparison of the effect of two different distributions of daily calcium intake.
1995,
Pubmed Gunshin,
Cloning and characterization of a mammalian proton-coupled metal-ion transporter.
1997,
Pubmed
,
Xenbase Gunshin,
Slc11a2 is required for intestinal iron absorption and erythropoiesis but dispensable in placenta and liver.
2005,
Pubmed Hallberg,
Calcium: effect of different amounts on nonheme- and heme-iron absorption in humans.
1991,
Pubmed Hallberg,
Does calcium interfere with iron absorption?
1998,
Pubmed Hallberg,
Bioavailability in man of iron in human milk and cow's milk in relation to their calcium contents.
1992,
Pubmed Mackenzie,
Iron Imports. II. Iron uptake at the apical membrane in the intestine.
2005,
Pubmed Mackenzie,
Functional properties of multiple isoforms of human divalent metal-ion transporter 1 (DMT1).
2007,
Pubmed
,
Xenbase Mackenzie,
Divalent metal-ion transporter DMT1 mediates both H+ -coupled Fe2+ transport and uncoupled fluxes.
2006,
Pubmed
,
Xenbase Perales,
Fortification of milk with calcium: effect on calcium bioavailability and interactions with iron and zinc.
2006,
Pubmed Shawki,
Interaction of calcium with the human divalent metal-ion transporter-1.
2010,
Pubmed
,
Xenbase Silanikove,
Use of an ion-selective electrode to determine free Ca ion concentration in the milk of various mammals.
2003,
Pubmed Su,
The G185R mutation disrupts function of the iron transporter Nramp2.
1998,
Pubmed Tandy,
Nramp2 expression is associated with pH-dependent iron uptake across the apical membrane of human intestinal Caco-2 cells.
2000,
Pubmed Toyohara,
Scallop DMT functions as a Ca2+ transporter.
2005,
Pubmed
,
Xenbase Xu,
A spontaneous, recurrent mutation in divalent metal transporter-1 exposes a calcium entry pathway.
2004,
Pubmed
