is excess iron excreted from the body

What happens to excess iron in the body?

The body cannot excrete the extra iron fast enough, so it continues to build up. The body stores it in organ tissue, mainly in the liver, as well as the heart and the pancreas. There are several types of iron overload disorder.

Is iron excretion related to body weight during menstruation?

Iron excretion was not strongly related to body weight. Body iron in menstruating women decreased somewhat (by 4.6%) in the men and tended to increase (by 1.5%) during the study.

How much iron is excreted from the body?

The range of iron excretion results in the present study would be further narrowed to 0.49–2.07 mg/d if we, like Green et al, had eliminated the nonsignificant long-term retention plots ( n = 4) that, in our retention plots, had flat slopes but an acceptable goodness of linear fit.

What does iron bind to in the human body?

Iron that we take in through our food generally binds to a protein called transferrin and circulates around in our blood plasma. For the most part, this iron is used to form hemoglobin, the substance in red blood cells that transports oxygen that we breathe into our tissues.

How is excess iron eliminated from the body?

Fe can be excreted by the liver into bile and transported into the small intestine, where it can undergo enterohepatic circulation or can be eliminated from the body via the feces.

What does the body do with excess iron?

Hereditary hemochromatosis (he-moe-kroe-muh-TOE-sis) causes your body to absorb too much iron from the food you eat. Excess iron is stored in your organs, especially your liver, heart and pancreas. Too much iron can lead to life-threatening conditions, such as liver disease, heart problems and diabetes.

How much iron is excreted from the body?

Normal daily loss of iron excreted through urine, vaginal fluid, sweat, feces, and tears total about 1-1.5 milligrams, or the equivalent of what most of us require per day to function normally.

Can the human body excrete iron?

Normally, if we have enough iron in our body, then no further iron is absorbed from the diet, and our iron levels remain relatively constant. But the body also has no way of excreting excess iron.

What is the most common cause of iron overload?

Mutations link in genes that control how the body absorbs iron cause primary hemochromatosis. The most common mutations are in the HFE link genes and are called C282Y and H63D.

What are the symptoms of high iron levels?

Symptoms of haemochromatosisfeeling very tired all the time (fatigue)weight loss.weakness.joint pain.an inability to get or maintain an erection (erectile dysfunction)irregular periods or absent periods.

How much iron do we lose a day?

about 1 mgThe typical adult — male or female — stores between 1–3 grams of iron in their body. Simultaneously, about 1 mg is lost daily due to the shedding of the skin and mucosal surfaces like that lining your gut ( 3 ). Women who menstruate need more iron. This is because blood contains about 70% of your body's iron.

Is iron excreted in urine?

However, iron is ultimately excreted in urine, which has been reported to include 62.4±4.1 µg/g creatinine (Cr) in healthy subjects [10]. Free reactive iron, unbound by its carrier proteins, may mediate oxidative stress in the renal tubules [6, 11].

How much iron do you lose in sweat?

22.5 micrograms iron/l sweatIron loss was directly related to the volume of sweat lost and amounted to 22.5 micrograms iron/l sweat. The findings indicate that iron is a physiological constituent of sweat and derived not only from contamination.

What foods are iron blockers?

Foods that may hinder iron absorptionPhytate, or phytic acid, is found in foods like whole grains, cereals, soy, nuts, and legumes ( 3 ). ... Even a small amount of phytate can significantly decrease iron absorption ( 1 ).But some evidence shows that it hinders the absorption of heme and non-heme iron ( 1 ).More items...

What is considered a dangerously high ferritin level?

Many laboratories consider serum ferritin levels greater than 200 ng/mL in women and greater than 300 ng/mL in men to be abnormal.

What blocks the absorption of iron?

Calcium (like iron) is an essential mineral, which means the body gets this nutrient from diet. Calcium is found in foods such as milk, yogurt, cheese, sardines, canned salmon, tofu, broccoli, almonds, figs, turnip greens and rhubarb and is the only known substance to inhibit absorption of both non-heme and heme iron.

Can too much iron affect your kidneys?

While iron therapy is a common treatment for such patients, new evidence suggests that iron is potentially toxic and its long-term consequences are unknown. Given that intravenous iron can damage normal kidneys, its potential toxicity might be even greater in kidneys affected by disease.

Does high iron make you tired?

Sufferers may experience a range of symptoms including fatigue, joint pain, weakness, weight loss and abdominal pain. Over time, the excess iron accumulates in specific areas of the body, eventually causing damage to tissues and organs including the liver and heart.

What are warning signs of hemochromatosis?

Symptoms of hemochromatosis include:Pain in your joints, especially your knuckles.Feeling tired.Unexplained weight loss.Skin that has a bronze or gray color.Pain in your belly.Loss of sex drive.Loss of body hair.Heart flutter.More items...•

Can too much iron cause thyroid problems?

Iron may have caused injury to the thyroid, followed by the development of antithyroid antibodies and hypothyroidism. The frequency of thyroid disorders in men with hemochromatosis is about 80 times that of men in the general population.

What is the recommended iron level for women?

Current iron recommendations for women are intended to maintain sufficient body iron for functional needs, with minimal iron stores, as indicated by a serum ferritin concentration of 15 μg/L ( 16 ). Subjects with this minimal level of body iron are estimated to absorb 18% of the iron from a high-bioavailability diet ( 16 ), an efficiency confirmed in our previous study of women’s iron absorption from high- and low-bioavailability diets ( 11 ). However, in that same study ( 11 ), one-third (week 0) to one-half (week 10) of the women, generally with serum ferritin values <15 μg/L, absorbed >18% of the iron from the high-bioavailability diet (11; individual results previously reported as group summaries). In the present study, 4 of the 19 menstruating women had average serum ferritin concentrations <15 μg/L, but only one developed iron deficiency anemia. Together, these data suggest that the upper ends of the distributions of both iron excretion and iron absorption by menstruating women are greater than have been used in deriving current recommendations.

What is the turnover rate of iron?

Iron excretion measurements, as reported herein, involve relatively sensitive determinations of iron turnover rates based on isotope dilution, combined with estimates of the size of the exchangeable body iron pool. Previously reported turnover rates are comparable but tend to be slightly greater than the present measurements for men and slightly less than the present measurements for menstruating women. For men (excluding the Bantu, who commonly have unusually high iron stores), Green et al ( 2) reported turnover rates of 10.8 ± 4.1%, 12.4 ± 4.8%, and 14.1 ± 2.5% and Heinrich ( 20) reported rates of 11.7 ± 12.7% and 11.7 ± 8.8% compared with 9.7 ± 3.6% per year in the present study ( Table 1 ). If the present study had excluded the 4 men with nonsignificant retention plots, the mean would increase from 9.7% to 10.7% per year. For menstruating women, Heinrich ( 20) reported turnover rates of 19.0 ± 11.8% ( n = 13) and 18.3 ± 7.1% ( n = 6), with a range of 8.0–40.2%. Our somewhat greater turnover rates of 28.6 ± 21.8% (arithmetic mean ± SD), with a range of 9.3–95.6% per year ( n = 19), reflect a highly skewed distribution with some very high excretion rates and are best expressed as a geometric mean of 23.3, as shown in Table 1. For nonmenstruating women, Heinrich ( 20) reported turnover rates of 13.9 ± 13.1%/y ( n = 4), which are generally consistent with measurements of 15.3 ± 3.1%/y ( n = 5) in the present study.

How much iron is excreted during menstruation?

Results: The total median (range) iron excretion was 1.18 (0.11–2.07) mg/d for 29 men, 1.58 (0.65–4.88) mg/d for 19 menstruating women, and 0.99 (0.86–1.57) for 5 postmenopausal women. When hormonal contraceptive users were omitted, the median for 15 menstruating women increased to 1.66 mg/d. The distribution of iron excretion was normal for the men and postmenopausal women and was highly skewed for the menstruating women; menstrual iron accounted for 90% of the variation. Iron excretion was not strongly related to body weight. Body iron in menstruating women decreased somewhat (by 4.6%) in the men and tended to increase (by 1.5%) during the study.

What is the mean of iron excretion?

Mean (± SD) iron excretion by the 29 men was 1.07 ± 0.47 (range: 0.11–2.07 mg/d) ( Table 1 ); the data are described as an arithmetic mean ± SD because they followed a normal distribution, as indicated by the Shapiro-Wilk test ( W = 0.97, P < 0.67) ( Figure 2 ). In contrast, iron excretion by the menstruating women was highly skewed, with a geometric mean of 1.69 and a range of 0.65–4.88 mg/d ( n = 19). Iron excretion was greater after the 4 subjects who used hormonal contraceptives were eliminated, which resulted in a geometric mean of 1.89 mg/d. Iron excretion for the 5 postmenopausal women was similar to that for the men: 1.08 ± 0.28 (0.86–1.57) mg/d. Described by using median values, iron excretion was 1.18 mg/d for the men, 1.58 mg/d for the menstruating women, 1.66 mg/d for the menstruating women not using hormonal contraceptives, and 0.99 mg/d for the postmenopausal women.

How much iron is excreted in men?

Mainly because of these differences in exchangeable body iron, the present iron excretion results for men (1.07 mg/d; range: 0.11–2.07 mg/d) are somewhat greater than those reported by Green et al ( 2 ): 0.95, 0.90, and 1.02 (range: 0.49–1.63) mg/d for 3 groups (excluding the Bantu). The range of iron excretion results in the present study would be further narrowed to 0.49–2.07 mg/d if we, like Green et al, had eliminated the nonsignificant long-term retention plots ( n = 4) that, in our retention plots, had flat slopes but an acceptable goodness of linear fit. Overall, these comparisons generally validate the present data, which extend human iron excretion results to include women.

How much iron is in the body?

The body’s iron content of ≈1.5–6 g is mainly controlled at the site of intestinal absorption, with an absorptive efficiency that can be up-regulated ≥15-fold in inverse proportion to body iron stores ( 1 ). Excluding iron losses from menstruation, other bleeding, or pregnancy, body iron is highly conserved. Basal iron excretion, principally from cellular exfoliation, is limited, and is the primary factor determining men’s nutritional requirements for absorbed iron. Using isotope dilution methods, Green et al ( 2) measured basal iron losses of 0.95 ± 0.30 mg/d for white men in the United States, 0.90 ± 0.31 mg/d for Mestizo men in Venezuela, and 1.02 ± 0.22 mg/d for Indian men in South Africa. Higher and more variable losses of 2.42 ± 1.09 and 2.01 ± 0.94 mg/d for Bantu men in Johannesburg and Durban, South Africa, respectively, were attributed to greater than normal body iron stores in the Bantu population. Since publication in 1968, the iron excretion measurements made by Green et al in the non-Bantu men have been used as the principal basis for factorial estimations of dietary iron requirements and recommendations for US men. They are further used to estimate basal iron losses of women and children, for whom direct measurements of basal iron excretion have been unavailable ( 3 ).

How is iron excreted in physiology?

Physiologic iron excretion was calculated by subtracting from this body iron loss the iron removed as part of the present investigation or medical care. This was determined from the volume of blood removed by phlebotomy, which averaged 0.2 (range: 0.1–0.3) mL/d by using the most recent hemoglobin concentration and the conversion factor 3.39 mg Fe/g hemoglobin ( 16 ).

What enzyme is used to reduce ferric iron?

Ferric iron (Fe3+) in the intestinal lumen must be reduced to ferrous iron (Fe2+) by duodenal cytochrome B reductase (DcytB) before uptake by DMT1. The iron within enterocytes can either be stored as ferritin, or transferred into the bloodstream via the protein ferroportin.

How does hepcidin work?

Hepcidin functions by directly binding to ferroportin, resulting in its degradation and therefore preventing iron from leaving the cell. Hepcidin also functions by inhibiting transcription of the DMT1 gene, thus reducing iron absorption.

How much iron is needed for weight loss?

A well-balanced diet contains sufficient iron to balance this loss, as approximately 10% of the 10-20 mg dietary iron in a balanced diet is absorbed each day. This iron can be haem iron from animal sources, or non-haem iron from wholegrains, nuts, seeds, legumes, and leafy greens.

What is the peptide that binds to ferroportin?

The absorption of iron is primarily regulated by a peptide called hepcidin, which is expressed by the liver. Hepcidin functions by directly binding to ferroportin, resulting in its degradation and therefore preventing iron from leaving the cell.

What is HHC in the body?

HHC is an autosomal recessive disease characterised by excessive absorption of dietary iron. As there is no system for the excretion of excess iron, iron accumulates in tissues and organs, disrupting normal function. The most susceptible organs include liver, adrenal glands, heart, joints, and pancreas.

Why are complex regulatory systems in place?

In order to overcome this potential toxicity, complex regulatory systems are in place to ensure the safe absorption, transportation and utilisation of iron.

Why is GI deficiency secondary to increased utilisation?

It can be secondary to increased utilisation due to physiological reasons such as pregnancy, or it may be a sign of pathology such as bleeding from the GI tract.

How is iron overload treated?

There are two main ways that iron overload is treated—therapeutic phlebotomy and iron chelation therapy.

How much ferritin is in a healthy man?

Healthy men usually have a serum ferritin of 24 to 336 micrograms per liter (mcg/L); healthy women's results are usually 12 to 307 mcg/L. Serum ferritin levels increase as the amount of NTBI increases in the blood, and results that are greater than 1,000 mcg/L indicate iron overload. 9 .

What is hemochromatosis caused by?

4  It is caused by mutations in genes that increase the absorption of iron from the diet.

What is iron overload?

Iron overload is an excess storage of iron in the body. It can occur for a few different reasons. Primary iron overload is caused by hemochromatosis, an inherited condition. But it may also develop secondary to multiple blood transfusions, which may be needed by those with types of blood cancer.

What happens when iron is too much?

When iron has overwhelmed the body’s ability to safely store it, it can cause harm in a number of ways: When there is more iron in the body than transferrin for it to bind to, it circulates around by itself as non-transferrin-bound iron (NTBI).

How much iron is lost in a day?

In healthy individuals, only about 1 to 2 milligrams (mg) of iron is turned over in a given day—that is, iron that’s taken in from the diet and lost through the shedding of skin cells and gastrointestinal cells, for instance. 6 

What are the consequences of iron overload?

Some evidence also suggests bacterial infection may be one of the consequences of iron overload, as iron buildup in the white blood cells impairs their ability to fight invading organisms. 4 

What is the gene that controls the amount of iron that the body absorbs?

Hereditary hemochromatosis occurs due to a mutation in a gene called HFE. This gene controls the amount of iron that the body absorbs. Two possible mutations in the HFE gene are C282Y and H63D.

How many copies of C282Y are there?

Trusted Source. with inherited hemochromatosis have inherited two copies of C282Y, one from the mother and the other from the father. A person who inherits just one faulty gene is not certain to develop iron overload syndrome, but they will be a carrier, and they will probably absorb more iron than normal.

What is the earliest age you can get a hematosis?

Iron builds up earlier in life, and symptoms appear between the ages of 15 and 30 years. Symptoms include diabetes and problems with sexual development.

What causes the body to store too much iron?

Causes. Risk factors. Symptoms. Diagnosis. Treatment. Complications. Summary. Iron overload disorders are a group of medical conditions that cause the body to store excess iron. They include hereditary hemochromatosis, a genetic condition in which a person’s body absorbs too much iron from foods and drinks.

What organs do you need to store iron?

The body cannot excrete excess iron, so it stores it in certain organs, notably the liver, heart, and pancreas , which can lead to organ damage. Damage to the pancreas can cause diabetes. Excess iron can, without treatment, also turn the skin a bronze color.

Why do women lose iron?

The reason for this is that most females regularly lose blood during menstruation, and blood loss reduces iron levels. Males may develop symptoms at the age of about 40–60 years. Trusted Source. , and females may have symptoms after menopause.

Why does iron accumulate so fast in the liver?

Research suggests that the cause is not genetic. It may happen because the mother’s immune system produces antibodies that damage the fetal liver.

What are the symptoms of excess iron?

Unfortunately, the signs and symptoms of excess iron can be easily confused with other conditions, and not diagnosing and managing this dangerous situation early enough can lead to disaster. Here’s how to tell if that’s your case, and how to get on top of it.

What is the bioenergetic circuit?

The bioenergetic circuit – too much iron can build-up in the liver and pancreas, both of which are part of this NEM circuit. Iron toxicity in the pancreas can lead to increased risk of diabetes, while iron toxicity in the liver can cause liver damage.

What hormones are produced by adrenal glands?

This gradual build-up of iron in the system creates chronic stress, which makes the adrenal glands work overtime to secrete the body’s main anti-stress hormone, cortisol, in order to deal with this stress. At first, cortisol levels rise, marking the beginning stages of Adrenal Fatigue Syndrome (AFS).

How does iron affect the NEM?

Here’s how excess iron will affect the NEM’s circuits: The cardionomic circuit – too much iron can damage the heart and blood vessels that are part of this NEM circuit. This is especially risky for those over 40 and those with hemochromatosis.

How to get iron levels back to normal?

You should also get a lot of rest and sleep, manage your stress, and do very gentle forms of exercise, such as adrenal breathing and adrenal yoga exercises . Over time, your body will balance itself out and your iron levels will go back to normal.

What is the NEM?

The NEM is your body’s global response to stress, and it involve s five other circuits besides the hormone circuit: the bioenergetic, the cardionomic, the neuroaffect, the inflammation, and the detoxification circuits. Here’s how excess iron will affect the NEM’s circuits: The cardionomic circuit – too much iron can damage ...

Why do we need a genetic test for hemochromatosis?

Genetic test – because the results of the tests above may be due to excess iron from supplementation, getting a genetic test done can help determine if you have hemochromatosis. This is important because those with hemochromatosis may need go beyond simply inhibiting iron intake to see improvement.

Why is iron overload bad?

It is caused by the body’s regulatory system failing to keep iron levels within healthy limits. For most people, iron overload is not a concern. However, it is a problem for those who are genetically predisposed to excessive absorption of iron from the digestive tract.

How does the body regulate iron levels?

The body regulates iron levels by adjusting the rate of iron absorption from the digestive tract. Hepcidin, the body’s iron-regulatory hormone, is responsible for keeping iron stores in balance. Its main function is to suppress the absorption of iron. Basically, this is how it works ( 4. Trusted Source.

Why is iron so tightly regulated?

There are two reasons why iron levels are tightly regulated within the body: Iron is an essential nutrient that plays a role in many basic body functions, so we must get a small amount. High levels of iron are potentially toxic, so we should avoid getting too much.

What is the role of iron in the body?

It is a crucial part of hemoglobin, a protein found in red blood cells. Hemoglobin is responsible for delivering oxygen to all of the body’s cells . There are two types of dietary iron:

Why is iron important for the immune system?

The immune system uses iron to kill harmful bacteria, so some amount of iron is needed to fight infections. Elevated levels of free iron stimulate the growth of bacteria and viruses, so too much iron can have the opposite effect and increase the risk of infections. ).

Where is heme iron found?

Heme iron: This type of iron is only found in animal foods, mostly in red meat. It is absorbed more easily than non-heme iron. Non-heme iron: Most dietary iron is in the non-heme form. It is found in both animals and plants.

How to get rid of iron?

The body has no easy way to dispose of extra iron. The most effective way to get rid of excess iron is blood loss.

How long does it take for iron to restock?

If your ferritin levels are low, it can take six months to a year for your body to restock its iron stores. The ferritin test is a simple blood test. High levels of ferritin can indicate an iron storage disorder, such as haemochromatosis, or a chronic disease process, while low levels of ferritin indicate possible iron deficiency, which causes anemia, a reduction in the number of oxygen-carrying red blood cells.

Why do my lips look pale?

Anemia tends to make you pale, and this is often most obvious at the lips [PDF link]. If your lips seem paler than usual, that’s an indicator of anemia.

What does it mean when your eye ring is pink?

Look for the pink (Red) ring just inside the eye (of any coloration of person ). If it is absent, it is a very positive sign of anemia,

What to do if your iron is low?

If your iron (ferritin) levels are low, you'll be advised to take an iron supplement until levels reach normal levels, and will need regular blood tests to monitor your iron levels .

What is the function of hemoglobin?

The body needs iron for growth and development , and of course for haemoglobin, and to make some hormones. Extra iron to your current needs is stored in your liver and is used by the body when your dietary intake is too low. Long term, if you don't have enough iron in your diet, your body's iron stores get lower over time.

Why do my nails turn pale?

This tip is considered a bit less reliable for people of color because the skin under nails can be many shades of brown, pink and even yellow with warmer skin tones.

How to remove iron from the body?

The best way for men, and postmenopausal women, to remove iron from the body is to donate blood.

Why is hepcidin important?

The regulation of iron homeostasis by inflammatory stimuli is important in the innate immune response to infections and cancers. Increasing hepcidin levels during infection has the effect of sequestering iron in tissues and reducing serum iron levels, effectively withholding iron from invading pathogens. Over prolonged periods of time, such as during chronic inflammation, this can result in reduced iron availability for the production of red blood cells and resultant anaemia. It is thought that elevated hepcidin levels are a major contributor to the anaemia of chronic disease, the most common form of anaemia in hospitalised patients.98, 99

What causes anaemia in mice?

The erythroid bone marrow has a high demand for iron, hence mutation or deletion of genes involved in the uptake of transferrin-bound iron in humans and mice lead to varying degrees of anaemia due to a decrease in the transport of iron into cells. For example, deletion of TFR1 in mice results in embryonic lethality due to severe anaemia.25Mutations in DMT1 lead to microcytic anaemia in mice and rats.15, 26Humans with DMT1 mutations also develop microcytic anaemia, however, unlike in mice and rats, this is also accompanied by liver iron overload.27STEAP3 mutations also cause a form of microcytic anaemia in humans and mice.28

How does iron help the immune system?

Regulating iron levels during infections is also important in the innate immune response to pathogens. To meet the body’s requirements for iron, elaborate mechanisms have evolved to sense iron levels and adjust iron absorption and recycling accordingly to maintain iron homeostasis. These mechanisms also respond to inflammatory/infectious stimuli, as well as hypoxia and erythropoietic signals, to either decrease or increase iron availability. The mechanisms regulating systemic iron homeostasis are largely centred on the liver and involve two molecules, hepcidin and ferroportin, that work together to regulate the flow of iron from cells into the systemic circulation. The diagram in figure 1summarises the most important players involved in the systemic regulation of iron homeostasis.

How much iron is absorbed daily?

Approximately 2 mg of iron is absorbed daily in the duodenum and proximal jejunum. This is balanced by losses resulting from the desquamation of skin, sloughing of intestinal epithelial cells and blood loss. The human body has no controlled mechanisms for the excretion of iron and the levels are balanced by regulating iron absorption. Iron in the diet can be in the form of haem or non-haem iron. As most non-haem iron in the diet is in the ferric form, it first needs to be reduced to Fe2+before it can be absorbed; this can be achieved by the actions of the membrane bound ferric reductase duodenal cytochrome B (DCYTB or CYBRD1), which is expressed on the apical brush border membrane of intestinal epithelial cells.13Ferrous iron is then transported across the apical membrane of enterocytes by the divalent metal transporter 1 (DMT1), an integral 12 transmembrane domain protein that has the ability to transport a number of divalent cations including Fe2+.14, 15To enter the systemic circulation iron must cross the basolateral membrane of intestinal enterocytes. This is achieved by the only known iron exporter, ferroportin, a 12 transmembrane domain protein, encoded by the SLC40A1gene.16–18. Ferroportin is also required for the release of iron from other cell types, in particular macrophages and hepatocytes where it is also highly expressed.18The release of ferrous iron from stores by ferroportin is assisted by the copper-containing ferroxidase enzyme caeruloplasmin19or, in the intestine, by its membrane-bound counterpart hephaestin.20These enzymes oxidise Fe2+to Fe3+before the iron binds to the iron-transport protein transferrin.

Which BMPs regulate hepcidin?

Many BMPs can upregulate hepcidin expression in vitro, including BMPs 2, 4, 5, 6, 7 and 9. 90The BMP that appears to be most physiologically relevant to the regulation of iron homeostasis is BMP6. It was shown that iron regulates the expression of BMP6in the liver91and that knockout of Bmp6in mice results in severe iron overload due to hepcidin deficiency.92, 93Which cell types contribute to BMP6expression and how it is upregulated by iron are not yet fully understood, although it has been suggested that BMP6 expressed in nonparenchymal cells of the liver can be regulated by iron and may function in a paracrine manner to regulate hepcidin in hepatocytes.94

Where is iron transported?

Iron is transported in the circulation bound to transferrin , although circulating iron can also exist in a non-transferrin bound form, especially when serum iron levels are high and transferrin is saturated, as is the case in HH and other iron loading conditions.21Transferrin receptor 1 (TFR1) is expressed ubiquitously on the cell surface and is responsible for taking up transferrin-bound iron through well studied mechanisms that involve receptor mediated endocytosis.22Once internalised the endocytic vesicles are acidified, allowing iron to be released from transferrin, and the apotransferrin, still bound to TFR1, recycled back to the cell surface where it is released.22Iron exits the endosome and enters the cytoplasm of cells via DMT1. The ferrireductase six-transmembrane epithelial antigen of the prostate 3 (STEAP3) also facilitates this process by reducing Fe3+to Fe2+prior to transport through DMT1.23The levels of many iron metabolism related proteins, including TFR1 and DMT1, are regulated at the post-transcriptional level via the iron responsive element/iron responsive protein (IRE/IRP) system. IRE-stem loop structures in the 3′ untranslated regions (UTRs) of these mRNAs bind to IRPs 1 or 2 under conditions of iron deficiency and stabilise the mRNA, enhancing translation of the proteins and increasing iron uptake. IREs are also present in the 5′UTRs of ferritin and ferroportin mRNAs among others and in contrast to TFR1 and DMT1, the translation of these proteins are repressed under iron deficient conditions. More details of this important and elegant system for balancing cellular iron homeostasis can be found elsewhere.24

What is the mechanism of uptake of non-transferrin bound iron?

Recently, a mechanism for the uptake of non-transferrin-bound iron (NTBI) was proposed that involves the zinc transporter, ZIP14 (SLC39A14).29Mice with ablation of SLC39A14 had markedly reduced uptake of NTBI in the liver and pancreas and ablation of SLC39A14 also prevented iron loading of the parenchymal cells in the liver and pancreas of mouse models of HH.29