Human iron metabolism: Difference between revisions
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'''Iron''' is an essential nutrient for human beings, although it can also be toxic. The most important role is in the [[heme]] protein of [[hemoglobin]] and [[cytochrome P-450]], and secondarily for [[myoglobin]], which transports oxygen into muscle cells. Iron also is a component of a number of enzymes. | '''Iron''' is an essential nutrient for human beings, although it can also be toxic. The most important role is in the [[heme]] protein of [[hemoglobin]] and [[cytochrome P-450]], and secondarily for [[myoglobin]], which transports oxygen into muscle cells. Iron also is a component of a number of enzymes. The greatest demand for iron is from [[erythropoesis]]: hemoglobin for the production of new [[erythrocyte]]s (i.e., red blood cells). <ref name=Munoz2009>{{citation | ||
| journal = World J Gastroenterol | year = 2009 | volume = 15 | issue = 37 | pages = 4617–4626. | |||
| doi= 10.3748/wjg.15.4617. | |||
| PMCID= PMC2754509 | |||
| title = An update on iron physiology | |||
| author = Munoz M, Villar I, Garcia-Erce JA | |||
| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2754509/?tool=pubmed}}</ref> | |||
Control mechanisms for iron metabolism are not fully understood, but there is increasing opinion that a peptide hormone produced in the liver, [[hepcidin]], is the "master controller." Originally thought to be an antibacterial substance, <ref>{{citation | Control mechanisms for iron metabolism are not fully understood, but there is increasing opinion that a peptide hormone produced in the liver, [[hepcidin]], is the "master controller." Originally thought to be an antibacterial substance, <ref>{{citation | ||
| Line 15: | Line 21: | ||
}}</ref> | }}</ref> | ||
==Requirements== | ==Requirements== | ||
The actual requirement for iron in food is quite low, as the body conserves iron stores. | The actual requirement for iron in food is quite low, as the body conserves iron stores. Erythropoiesis requires 20-30 mg/day, so, with efficient conservation, only 1-2 mg/day of dietary iron is needed. <ref name=Munoz2009 /> | ||
==Digestion== | ==Digestion== | ||
Iron, in food, is processed differently depending if it is in the form of heme (e.g., in meats) or in other molecules. As food breaks down in the [[stomach]], ferric (Fe<sup>+3</sup>) iron is reduced to ferrous (Fe<sup>+2</sup>) iron by the enzyme [[ferric reductase]]. [[Ascorbic acid]] and other reducing agents stimulates the reduction, and thus stimulates absorption. | Iron, in food, is processed differently depending if it is in the form of heme (e.g., in meats) or in other molecules. As food breaks down in the [[stomach]], ferric (Fe<sup>+3</sup>) iron is reduced to ferrous (Fe<sup>+2</sup>) iron by the enzyme [[ferric reductase]]. [[Ascorbic acid]] and other reducing agents stimulates the reduction, and thus stimulates absorption. | ||
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Iron loading increases hepcidin synthesis (i.e., reducing iron intake), while hypoxia and anemia decrease its production. <ref name=Ganz2005 /> | Iron loading increases hepcidin synthesis (i.e., reducing iron intake), while hypoxia and anemia decrease its production. <ref name=Ganz2005 /> | ||
Hepcidin is markedly induced during inflammation, | Hepcidin is markedly induced during inflammation, through the effect of [[interleukin|interleukin-6 (IL-6)]]. Increased hepcidin traps iron in [[macrophage]]s, decreases plasma iron concentrations, and is a mechanism of [[anemia of chronic disease]]. <ref name=Nemeth2004>{{citation | ||
| journal = J Clin Invest | year = 2004 | volume = 113 | issue = 9 | pages = 1271–1276. | |||
| doi = 10.1172/JCI200420945. | |||
| PMCID= PMC398432 | |||
| title = IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin | |||
| author = Nemeth E ''et al'' | |||
| url = http://www.ncbi.nlm.nih.gov/pmc/articles/PMC398432/}}</ref> | |||
==References== | ==References== | ||
{{reflist|2}} | {{reflist|2}} | ||
Revision as of 23:33, 2 January 2010
Iron is an essential nutrient for human beings, although it can also be toxic. The most important role is in the heme protein of hemoglobin and cytochrome P-450, and secondarily for myoglobin, which transports oxygen into muscle cells. Iron also is a component of a number of enzymes. The greatest demand for iron is from erythropoesis: hemoglobin for the production of new erythrocytes (i.e., red blood cells). [1]
Control mechanisms for iron metabolism are not fully understood, but there is increasing opinion that a peptide hormone produced in the liver, hepcidin, is the "master controller." Originally thought to be an antibacterial substance, [2] it is now believed to be an inhibitor of iron intake into the body. [3]
Requirements
The actual requirement for iron in food is quite low, as the body conserves iron stores. Erythropoiesis requires 20-30 mg/day, so, with efficient conservation, only 1-2 mg/day of dietary iron is needed. [1]
Digestion
Iron, in food, is processed differently depending if it is in the form of heme (e.g., in meats) or in other molecules. As food breaks down in the stomach, ferric (Fe+3) iron is reduced to ferrous (Fe+2) iron by the enzyme ferric reductase. Ascorbic acid and other reducing agents stimulates the reduction, and thus stimulates absorption.
Non-heme iron, however, may not be available to the digestive processes. While spinach is legendary as an iron source, the iron in raw spinach is bound into a non-absorbable oxalate. Cooking the spinach does make the iron bioavailable; the cartoon character Popeye the Sailor Man was correct in eating his spinach from a can.
Most actual absorption takes place in the duodenum. Heme is absorbed via the heme transporter protein. Non-heme iron enters the apical surface of the enterocytes lining the duodenum via divalent metal transporter 1 (DMT1)[4], carrying iron into the interstitial fluid by a protein called ferroportin (FP). [5]
Hepcidin binds to ferroportin, inhibiting its action. [3]
Distribution
Ferrous iron, in plasma, is reconverted to ferric, and bound to a carrier protein, ferritin.
Ferritin in plasma stays in equilibrium with ferritin in bone marrow, and plasma ferritin is indicative of actual iron stores in the marrow.
Excretion
Disorders of iron metabolism
Not all anemia is due to disorders of iron metabolism, but iron deficiency anemia is a syndrome commonly seen, with many causes. Iron in excess through a metabolic error is less common, and called hemochromatosis. Among children in the U.S., iron supplements are the most common source of serious accidental poisoning.
Iron loading increases hepcidin synthesis (i.e., reducing iron intake), while hypoxia and anemia decrease its production. [3]
Hepcidin is markedly induced during inflammation, through the effect of interleukin-6 (IL-6). Increased hepcidin traps iron in macrophages, decreases plasma iron concentrations, and is a mechanism of anemia of chronic disease. [6]
References
- ↑ 1.0 1.1 Munoz M, Villar I, Garcia-Erce JA (2009), "An update on iron physiology", World J Gastroenterol 15 (37): 4617–4626., DOI:10.3748/wjg.15.4617.
- ↑ Park CH et al. (2001), "Hepcidin, a Urinary Antimicrobial Peptide Synthesized in the Liver", Journal of Biological Chemistry 276: 7806-7810, DOI:10.1074/jbc.M008922200
- ↑ 3.0 3.1 3.2 Ganz T, Nemeth E (2005), "Iron imports. IV. Hepcidin and regulation of body iron metabolism", Am J Physiol Gastrointest Liver Physiol 290: G199–G203, DOI:10.1152/ajpgi.00412.2005
- ↑ Chong WS et al. (Advance Access originally published online on August 25, 2005), "Expression of divalent metal transporter 1 (DMT1) isoforms in first trimester human placenta and embryonic tissues", Human Reproduction 20 (12): 3532-3538, DOI:10.1093/humrep/dei246
- ↑ De Domenico, I et al. (2006), "Ferroportin-mediated mobilization of ferritin iron precedes ferritin degradation by the proteasome", EMBO Journal 25: 5396 - 5404, DOI:10.1038/sj.emboj.7601409
- ↑ Nemeth E et al (2004), "IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin", J Clin Invest 113 (9): 1271–1276., DOI:10.1172/JCI200420945.