Title: How Body Iron Stores Are Maintained

Key words: Iron absorption, bioavailability, iron storage, ferritins, transferrin

Date: May 1999

Category: 3. Micronutrients

Type: Article

Author: Dr van Rhijn

How Body Iron Stores Are Maintained

Introduction

Body iron content is kept within narrow limits, with loss and intake finely balanced. Absorption & transport mechanisms remain uncertain, but are closely related to body stores and bioavailability. The main factors affecting iron balance, intake, stores and loss, are discussed below.

Iron Absorption

Iron absorption (1 mg/d) is influenced by the bioavailability of dietary iron1, 2. The lumenal phase (haem - Fe2+ and non-haem – Fe3+) is primarily controlled by duodenal mucosal uptake regulation (integrin) and plasma iron transfer. Absorption, which is favoured by acids3 and inhibited by polyphenols & phytates4, is under strict control, depending on iron status to prevent overload5 in health. The poorly understood6 inorganic, transcellular iron uptake is energy requiring, saturable and electrogenic, facilitated by a carrier protein located exclusively at duodenal enterocyte brush borders and potential gradient mediated, via fatty acid-iron complex formation across cell membranes7, 8. This is a rate-limiting step, highly sensitive to changes in body iron requirement9. Haem-containing NAD reductase in brush border plays a role in converting Fe 3+ to Fe 2+ prior to incorporation into erythrocytes10.

Iron Storage

Iron uptake by mucosal cells is inversely proportional to total body iron (3-4 g in adults11). Iron is either incorporated into intracellular ferritin (local passive store), or transferred across the basal-lateral membrane (enterocyte) into plasma, independent of plasma iron or transferrin concentrations. Iron is predominantly stored in ferritin (20%) (24 apoferritin subunits, heavy & light types, storing 4500 Fe3+ inorganic complex atoms), to prevent excess iron from damaging cells12. Synthesis of ferritin is directly related to cellular iron concentration13 (body stores). Increased tissue ferritin (iron overload, haemochromatosis14, 15), is converted into the ferritin-derived, less soluble haemosiderin (10%), thereby reducing potential cellular iron toxicity five-fold16. Iron is conserved by an efficient internal recycling mechanism, and plasma transferrin-bound iron (3-4 mg) plays a central role in this exchange.

Transferrin17 (b -globulin protein), transfers tissue iron from reticuloendothelial cells, erythroid marrow, skeletal muscle cells, myoglobin (0.5 g), cytochrome enzymes (0.1 g) and hepatocyte parenchymal tissues (iron buffer) to iron requiring tissues (2.5–3g haemoglobin) via specific cellular transferrin receptors. The number of receptors is inversely related to availability of intracellular iron18. It is regulated by a cytosolic iron regulatory protein (IRP)19 which binds post-transcriptionally to iron responsive elements (IRE) in the messenger ribonucleic acid (mRNA) for both ferritin and transferrin receptors20.

A small pool of 'in transit' iron also plays a key role in iron physiology, prior to incorporation into iron-containing proteins. Serum transferrin receptor21 and serum ferritin22 saturation are indicators of iron status and control the overall iron intake23. A cut-off point of 25 - 30 m g/l indicates low iron stores24.

Iron Loss

Iron is lost from the gut (300-500 m g/day) and via urine, skin, sweat (0.5-1 mg/day) and menstruation (average 0.7 mg/day)25. Lack of an excretory mechanism for iron makes chelating agents or phlebotomy the only effective means of reducing iron in pathologically increased stores (haemochromatosis)26.

Conclusion

In the absence of an excretory pathway for iron, altering the amount of duodenal absorbed iron remains the primary regulatory mechanism of iron homeostasis, with contributions by interrelationships between the intra- and extra-cellular iron. The ability of ferritin to sequester iron gives it the dual functions of iron detoxification and iron reserve.

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