Physiology and molecular biology of dietary iron absorption

Annual Review of Nutrition

Volumn 23, Issue , 2003, Pages 283-301

  Miret, Silvia ^a   Simpson, Robert J ^a   McKie, Andrew T ^a  

^a KING'S COLLEGE LONDON   (United Kingdom)

Author keywords

Bioavailability; DCT1; Dcytb; DMT1; Ferroportin; Hepcidin; Hephaestin; HFE; Ireg1; MTP1; Nramp2; SLC 11A3

Indexed keywords

CERULOPLASMIN; FERRIC ION; FERROUS ION; FERROXIDASE HEPHAESTIN; HEME; HEPHAESTIN; IRON; UNCLASSIFIED DRUG;

ANEMIA; AUTOSOMAL DOMINANT DISORDER; BASOLATERAL MEMBRANE; DIFFUSION; DMT 1 GENE; ERYTHROPOIESIS; FERRIC REDUCTASE GENE; FERROPORTIN GENE; GENE; GENETIC DISORDER; HYPOXIA; INTESTINE ABSORPTION; INTESTINE MUCOSA; INTESTINE TRANSIT TIME; IREG 1 GENE; IRON ABSORPTION; IRON INTAKE; IRON METABOLISM; IRON STORAGE; IRON TRANSPORT; IRON TRANSPORT GENE; MEMBRANE POTENTIAL; MOLECULAR BIOLOGY; MTP 1 GENE; MUCUS; NRAMP 2 GENE; OXIDATION REDUCTION REACTION; PRIORITY JOURNAL; PROTON TRANSPORT; REVIEW; RODENT;

ANIMALS; BIOLOGICAL AVAILABILITY; HUMANS; INTESTINAL ABSORPTION; IRON, DIETARY; OXIDATION-REDUCTION;

RODENTIA;

EID: 0042866137     PISSN: 01999885     EISSN: None     Source Type: Book Series    
DOI: 10.1146/annurev.nutr.23.011702.073139     Document Type: Review

References (96)

1. Abboud S, Haile DJ. 2000. A novel mammalian iron-regulated protein involved in intracellular iron metabolism. J. Biol. Chem. 275:19906-12
2. Bannerman RM. 1965. Quantitative aspects of hemoglobin-iron absorption. J. Lab. Clin. Med. 65:944-50
3. Bannerman RM, Cooper RG. 1966. Sex-linked anemia: a hypochromic anemia of mice. Science 151:581-82
4. Beguin Y, Huebers HA, Josephson B, Finch CA. 1988. Transferrin receptors in rat plasma. Proc. Natl. Acad. Sci. USA 85:637-40
5. Benito P, Miller D. 1998. Iron absorption and bioavailability: an updated review. Nutr. Res. 18:581-603
6. Canonne-Hergaux F, Levy JE, Fleming MD, Montross LK, Andrews NC, Gros P. 2001. Expression of the DMT1 (NRAMP2/DCT1) iron transporter in mice with genetic iron overload disorders. Blood 97:1138-40
7. Cavill I. 1999. Iron status as measured by serum ferritin: the marker and its limitations. Am. J. Kidney Dis. 34:S12-17
8. Chua AC, Morgan EH. 1997. Manganese metabolism is impaired in the Belgrade laboratory rat. J. Comp. Physiol. [B] 167:361-69
9. Conrad ME, Schade SG. 1968. Ascorbic acid chelates in iron absorption: a role for hydrochloric acid and bile. Gastroenterology 55:35-45
10. Conrad ME, Umbreit JN, Moore EG. 1991. A role for mucin in the absorption of inorganic iron and other metal cations. A study in rats. Gastroenterology 100:129-36
11. Conrad ME, Weintraub LR, Crosby WH. 1964. The role of the intestine in iron kinetics. J. Clin. Invest. 43:963-74
12. Conrad ME, Weintraub LR, Sears DA, Crosby WH. 1966. Absorption of hemoglobin iron. Am. J. Physiol. 211:1123-30
13. Dahm LJ, Jones DP. 1994. Secretion of cysteine and glutathione from mucosa to lumen in rat small intestine. Am. J. Physiol. 267:G292-300
14. de Sousa M, Reimao R, Lacerda R, Hugo P, Kaufmann SH, Porto G. 1994. Iron overload in beta 2-microglobulin-deficient mice. Immunol. Lett. 39:105-11
15. Devalia V, Carter K, Walker AP, Perkins SJ, Worwood M, May A, Dooley JS. 2002. Autosomal dominant reticuloendothelial iron overload associated with a 3-base pair deletion in the ferroportin 1 gene (SLC11A3). Blood 100:695-97
16. Donovan A, Brownlie A, Zhou Y, Shepard J, Pratt SJ, et al. 2000. Positional cloning of zebrafish ferroportinl identifies a conserved vertebrate iron exporter. Nature 403:776-81
17. Duong LT, Fleming PJ, Russell JT. 1984. An identical cytochrome b561 is present in bovine adrenal chromaffin vesicles and posterior pituitary neurosecretory vesicles. J. Biol. Chem. 259:4885-89
18. Dupic F, Fruchon S, Bensaid M, Borot N, Radosavljevic M, et al. 2002. Inactivation of the hemochromatosis gene differentially regulates duodenal expression of iron-related mRNAs between mouse strains. Gastroenterology 122:745-51
19. Escriou V, Laporte F, Garin J, Brandolin G, Vignais PV. 1994. Purification and physical properties of a novel type of cytochrome b from rabbit peritoneal neutrophils. J. Biol. Chem. 269:14007-14
20. Escriou V, Laporte F, Vignais PV, Desbois A. 1997. Differential characterization of neutrophil cytochrome p30 and cytochrome b-558 by low-temperature absorption and resonance Raman spectroscopies. Eur. J. Biochem. 245:505-11
21. Fairweather-Tait S, Wright AJA. 1991. Small intestinal transit-time and iron-absorption. Nutr. Res. 11:1465-68
22. Feder JN, Penny DM, Irrinki A, Lee VK, Lebron JA, et al. 1998. The hemochromatosis gene product complexes with the transferrin receptor and lowers its affinity for ligand binding. Proc. Natl. Acad. Sci. USA 95:1472-77
23. Finch C. 1994. Regulators of iron balance in humans. Blood 84:1697-702
24. Flanagan PR, Haist J, Valberg LS. 1980. Comparative effects of iron deficiency induced by bleeding and a low-iron diet on the intestinal absorptive interactions of iron, cobalt, manganese, zinc, lead and cadmium. J. Nutr. 110:1754-63
25. Fleming MD, Romano MA, Su MA, Garrick LM, Garrick MD, Andrews NC. 1998. Nramp2 is mutated in the anemic Belgrade (b) rat: evidence of a role for Nramp2 in endosomal iron transport. Proc. Natl. Acad. Sci. USA 95:1148-53
26. Fleming MD, Trenor CC, Su MA, Foernzler D, Beier DR, et al. 1997. Microcytic anaemia mice have a mutation in Nramp2, a candidate iron transporter gene. Nat. Genet. 16:383-86
27. Fleming PJ, Kent UM. 1987. Secretory vesicle cytochrome b561: a transmembrane electron transporter. Ann. NY Acad. Sci. 493:101-7
28. Fleming RE, Sly WS. 2002. Mechanisms of iron accumulation in hereditary hemochromatosis. Annu. Rev. Physiol. 64:663-80
29. Frazer DM, Vulpe CD, McKie AT, Wilkins SJ, Trinder D, et al. 2001. Cloning and gastrointestinal expression of rat hephaestin: relationship to other iron transport proteins. Am. J. Physiol. Gastrointest. Liver Physiol. 281:G931-39
30. Frazer DM, Wilkins SJ, Becker EM, Murphy TL, Vulpe CD, et al. 2003. A rapid decrease in the expression of DMT1 and Dcytb but not Ireg1 or hephaestin explains the mucosal block phenomenon of iron absorption. Gut 52:340-46
31. Frazer DM, Wilkins SJ, Becker EM, Vulpe CD, McKie AT, et al. 2002. Hepcidin expression inversely correlates with the expression of duodenal iron transporters and iron absorption in rats. Gastroenterology 123:835-44
32. Golubov J, Flanagan P, Adams P. 1991. Inhibition of iron absorption by omeprazole in rat model. Dig. Dis. Sci. 36:405-8
33. Grasbeck R, Majuri R, Kouvonen I, Tenhunen R. 1982. Spectral and other studies on the intestinal heme receptor of the pig. Biochim. Biophys. Acta 700:137-42
34. Greenman J, Jacobs A. 1975. The effect of iron stores on iron absorption in the rat: the possible role of circulating ferritin. Gut 16:613-16
35. Gunshin H, Allerson CR, Polycarpou-Schwarz M, Rofts A, Rogers JT, et al. 2001. Iron-dependent regulation of the divalent metal ion transporter. FEBS Lett. 509:309-16
36. Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero ME et al. 1997. Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388:482-88
37. Gutteberg TJ, Rokke O, Andersen O, Jorgensen T. 1989. Early fall of circulating iron and rapid rise of lactoferrin in septicemia and endotoxemia: an early defence mechanism. Scand. J. Infect. Dis. 21:709-15
38. Hediger MA, Rolfs A, Goswami T. 2002. Iron transport and hemochromatosis. J. Investig. Med. 50:239S-46S
39. Hubert N, Hentze MW. 2002. Previously uncharacterized isoforms of divalent metal transporter (DMT)-1: implications for regulation and cellular function. Proc. Natl. Acad. Sci. USA 99:12345-50
40. Jacobs A, Miles PM. 1969. Intraluminal transport of iron from stomach to small-intestinal mucosa. Br. Med. J. 4:778-81
41. Krause A, Neitz S, Magert HJ, Schulz A, Forssmann WG, et al. 2000. LEAP-1, a novel highly disulfide-bonded human peptide, exhibits antimicrobial activity. FEBS Lett. 480:147-50
42. Lebron JA, Bennett MJ, Vaughn DE, Chirino AJ, Snow PM, et al. 1998. Crystal structure of the hemochromatosis protein HFE and characterization of its interaction with transferrin receptor. Cell 93:111-23
43. Lehrer RI, Ganz T. 2002. Defensins of vertebrate animals. Curr. Opin. Immunol. 14:96-102
44. Manis JG, Schachter D. 1962. Active transport of iron by intestine: features of the two-step mechanism. Am. J. Physiol. 203:73-80
45. McCance RA, Widdowson EM. 1937. Absorption and excretion of iron. Lancet 2:680-84
46. McKie AT, Barrow D, Latunde-Dada GO, Rolfs A, Sager G, et al. 2001. An iron-regulated ferric reductase associated with the absorption of dietary iron. Science 291:1755-59
47. McKie AT, Simpson RJ. 2002. Basolateral transport of iron in mammalian intestine: from physiology to molecules. In Molecular and Cellular Iron Transport, ed. DM Templeton, pp. 175-88. New York: Marcel Dekker
48. McKie AT, Marciani P, Rolfs A, Brennan K, Wehr K, et al. 2000. A novel duodenal iron-regulated transporter, IREG1, implicated in the basolateral transfer of iron to the circulation. Mol. Cell. 5:299-309
49. Montosi G, Donovan A, Totaro A, Garuti C, Pignatti E, et al. 2001. Autosomal-dominant hemochromatosis is associated with a mutation in the ferroportin (SLC11A3) gene. J. Clin. Invest. 108:619-23
50. Mulvihill B, Kirwan FM, Morrissey PA, Flynn A. 1998. Effect of myofibrillar muscle proteins on the in vitro bioavailability of non-haem iron. Int. J. Food Sci. Nutr. 49:187-92
51. Nicolas G, Bennoun M, Devaux I, Beaumont C, Grandchamp B, et al. 2001. Lack of hepcidin gene expression and severe tissue iron overload in upstream stimulatory factor 2 (USF2) knockout mice. Proc. Natl. Acad. Sci. USA 98:8780-85
52. Nicolas G, Bennoun M, Porteu A, Marivet S, Beaumont C, et al. 2002. Severe iron deficiency anemia in transgenic mice expressing liver hepcidin. Proc. Natl. Acad. Sci. USA 99:4596-601
53. Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, et al. 2002. The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J. Clin. Invest. 110:1037-44
54. O'Riordan DK, Sharp P, Sykes RM, Srai SK, Epstein O, Debnam ES. 1995. Cellular mechanisms underlying the increased duodenal iron absorption in rats in response to phenylhydrazine-induced hemeolytic anaemia [see comments]. Eur. J. Clin. Invest. 25:722-27
55. Park CH, Valore EV, Waring AJ, Ganz T. 2001. Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J. Biol. Chem. 276:7806-10
56. Park JD, Cherrington NJ, Klaassen CD. 2002. Intestinal absorption of cadmium is associated with divalent metal transporter 1 in rats. Toxicol. Sci. 68:288-94
57. Parkkila S, Waheed A, Britton RS, Feder JN, Tsuchihashi Z, et al. 1997. Immunohistochemistry of HLA-H, the protein defective in patients with hereditary hemochromatosis, reveals unique pattern of expression in gastrointestinal tract. Proc. Natl. Acad. Sci. USA 94:2534-39
58. Parmley RT, Barton JC, Conrad ME, Austin RL, Holland RM. 1981. Ultrastrucrural cytochemistry and radioautography of hemoglobin-iron absorption. Exp. Mol. Pathol. 34:131-44
59. Peppriell JE, Edwards JA, Bannerman RM. 1982. The kinetics of iron uptake by isolated intestinal cells from normal mice and mice with sex-linked anemia. Blood 60:635-41
60. Pietrangelo A. 2002. Physiology of iron transport and the hemochromatosis gene. Am. J. Physiol. Gastrointest. Liver Physiol. 282:G403-14
61. Pietrangelo A, Casalgrandi G, Quaglino D, Gualdi R, Conte D, et al. 1995. Duodenal ferritin synthesis in genetic hemochromatosis. Gastroenterology 108:208-17
62. Pigeon C, Ilyin G, Courselaud B, Leroyer P, Turlin B, et al. 2001. A new mouse liver-specific gene, encoding a protein homologous to human antimicrobial peptide hepcidin, is overexpressed during iron overload. J. Biol. Chem. 276:7811-19
63. Pountney DJ, Raja KB, Simpson RJ, Wrigglesworth JM. 1999. The ferric-reducing activity of duodenal brush-border membrane vesicles is associated with a b-type heme. Biometals 12:53-62
64. Powell JJ, Jugdaohsingh R, Thompson RP. 1999. The regulation of mineral absorption in the gastrointestinal tract. Proc. Nutr. Soc. 58:147-53
65. Powell JJ, Whitehead MW, Ainley CC, Kendall MD, Nicholson JK, Thompson RP. 1999. Dietary minerals in the gastrointestinal tract: hydroxypolymerisation of aluminium is regulated by luminal mucins. J. Inorg. Biochem. 75:167-80
66. Raffin SB, Woo CH, Roost KT, Price DC, Schmid R. 1974. Intestinal absorption of hemoglobin iron-heme cleavage by mucosal heme oxygenase. J. Clin. Invest. 54:1344-52
67. Raja KB, Simpson RJ, Peters TJ. 1992. Investigation of a role for reduction in ferric iron uptake by mouse duodenum [erratum published in Biochim. Biophys. Acta 1993 Mar. 10, 1176(1-2):197]. Biochim. Biophys. Acta 1135:141-46
68. Roetto A, Merryweather-Clarke AT, Daraio F, Livesey K, Pointon JJ, et al. 2002. A valine deletion of ferroportin 1: a common mutation in hemochromastosis type 4. Blood 100:733-34
69. Roetto A, Papanikolaou G, Politou M, Alberti F, Girelli D, et al. 2003. Mutant antimicrobial peptide hepcidin is associated with severe juvenile hemochromatosis. Nat. Genet. 33(1):21-22
70. Said HM, Blair JA, Lucas ML, Hilburn ME. 1986. Intestinal surface acid microclimate in vitro and in vivo in the rat. J. Lab. Clin. Med. 107:420-24
71. Schade SG, Felsher BF, Conrad ME. 1969. An effect of intestinal motility on iron absorption. Proc. Soc. Exp. Biol. Med. 130:757-61
72. Schumann K, Elsenhans B, Ehtechami C, Forth W. 1990. Increased intestinal iron absorption in rats with normal hepatic iron stores. Kinetic aspects of the adaptative response to parenteral iron repletion in dietary iron deficiency. Biochim. Biophys. Acta 1033:277-81
73. Schumann K, Elsenhans B, Forth W. 1999. Kinetic analysis of 59Fe movement across the intestinal wall in duodenal rat segments ex vivo. Am. J. Physiol. 276:G431-40
74. Schumann K, Moret R, Kunzle H, Kuhn LC. 1999. Iron regulatory protein as an endogenous sensor of iron in rat intestinal mucosa. Possible implications for the regulation of iron absorption. Eur. J. Biochem. 260:362-72
75. Simpson RJ, Peters TJ. 1990. Forms of soluble iron in mouse stomach and duodenal lumen: significance for mucosal uptake. Br. J. Nutr. 63:79-89
76. Skikne BS, Lynch SR, Robinson RG, Spicer JA, Cook JD. 1983. The effect of food consistency on iron absorption. Am. J. Gastroenterol. 78:607-10
77. Srivastava M, Duong LT, Fleming PJ. 1984. Cytochrome b561 catalyzes transmembrane electron transfer. J. Biol. Chem. 259:8072-75
78. Stewart CA, Termanini B, Sutliff VE, Serrano J, Yu F, et al. 1998. Iron absorption in patients with Zollinger-Ellison syndrome treated with long-term gastric acid antisecretory therapy. Aliment. Pharmacol. Ther. 12:83-98
79. Tandy S, Williams M, Leggett A, Lopez-Jimenez M, Dedes M, et al. 2000. Nramp2 expression is associated with pH-dependent iron uptake across the apical membrane of human intestinal Caco-2 cells. J. Biol. Chem. 275:1023-29
80. Tchernitchko D, Bourgeois M, Martin ME, Beaumont C. 2002. Expression of the two mRNA isoforms of the iron transporter Nrmap2/DMTI in mice and function of the iron responsive element. Biochem. J. 363:449-55
81. Tennant J, Stansfield M, Yamaji S, Srai S, Sharp P. 2002. Effects of copper on the expression of metal transporters in human intestinal Caco-2 cells. FEBS Lett. 527:239
82. Trinder D, Oates PS, Thomas C, Sadleir J, Morgan EH. 2000. Localisation of divalent metal transporter 1 (DMT1) to the microvillus membrane of rat duodenal enterocytes in iron deficiency, but to hepatocytes in iron overload [see comments]. Gut 46:270-76
83. Trinder D, Olynyk JK, Sly WS, Morgan EH. 2002. Iron uptake from plasma transferrin by the duodenum is impaired in the Hfe knockout mouse. Proc. Natl. Acad. Sci. USA 99:5622-26
84. Turnbull A, Cleton F, Finch CA. 1962. Iron absorption. IV. The absorption of hemoglobin iron. J. Clin. Invest. 41:1897-1907
85. Vulpe CD, Kuo YM, Murphy TL, Cowley L, Askwith C, et al. 1999. Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse. Nat. Genet. 21:195-99
86. Waheed A, Grubb JH, Zhou XY, Tomatsu S, Fleming RE, et al. 2002. Regulation of transferrin-mediated iron uptake by HFE, the protein defective in hereditary hemochromatosis. Proc. Natl. Acad. Sci. USA 99:3117-22
87. Weintraub LR, Conrad ME, Crosby WH. 1965. Absorption of hemoglobin iron by the rat. Proc. Soc. Exp. Biol. Med. 120:840-43
88. Wheby MS, Jones LG, Crosby WH. 1964. Studies on iron absorption. Intestinal regulatory mechanisms. J. Clin. Invest. 43:1433-42
89. Wheby MS, Suttle GE, Ford KT III. 1970. Intestinal absorption of hemoglobin iron. Gastroenterology 58:647-54
90. Wien EM, Van Campen DR. 1991. Ferric iron absorption in rats: relationship to iron status, endogenous sulfhydryl and other redox components in the intestinal lumen. J. Nutr. 121:825-31
91. Wien EM, Van Campen DR. 1991. Mucus and iron absorption regulation in rats fed various levels of dietary iron. J. Nutr. 121:92-100
92. Wien EM, Van Campen DR. 1994. Enhanced Fe(3+)-reducing capacity does not seem to play a major role in increasing iron absorption in iron-deficient rats. J. Nutr. 124:2006-15
93. Wienk KJ, Marx JJ, Beynen AC. 1999. The concept of iron bioavailability and its assessment. Eur. J. Nutr. 38:51-75
94. Worthington MT, Cohn SM, Miller SK, Luo RQ, Berg CL. 2001. Characterization of a human plasma membrane heme transporter in intestinal and hepatocyte cell lines. Am. J. Physiol. Gastrointest. Liver Physiol. 280:G1172-77
95. Yamaji S, Tennant J, Tandy S, Williams M, Singh Srai SK, Sharp P. 2001. Zinc regulates the function and expression of the iron transporters DMT1 and IREG1 in human intestinal Caco-2 cells. FEBS Lett. 507:137-41
96. Zoller H, Koch RO, Theurl I, Obrist P, Pietrangelo A, et al. 2001. Expression of the duodenal iron transporters divalent-metal transporter 1 and ferroportin 1 in iron deficiency and iron overload. Gastroenterology 120:1412-19