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PubMed2000

Involvement of iron (ferric) reduction in the iron absorption mechanism of a trivalent iron-protein complex (iron protein succinylate).

Iron protein succinylate is a non-toxic therapeutic iron compound. We set out to characterise the structure of this compound and investigate the importance of digestion and intestinal reduction in determining absorption of the compound. The structure of the compound was investigated by variable temperature Mössbauer spectroscopy, molecular size determinations and kinetics of iron release by chelators. Intestinal uptake was determined with radioactive compound force fed to mice. Reduction of the compound was determined by in vitro incubation with intestinal fragments. The compound was found to contain only ferric iron, present as small particles including sizes below 10 nm. The iron was released rapidly to chelators. Digestion with trypsin reduced the molecular size of the compound. Intestinal absorption of the compound was inhibited by a ferrous chelator (ferrozine), indicating that reduction to ferrous iron may be important for absorption. The native compound was a poor substrate for duodenal reduction activity, but digestion with pepsin, followed by pancreatin, released soluble iron complexes with an increased reduction rate. We conclude that iron protein succinylate is absorbed by a mechanism involving digestion to release soluble, available ferric species which may be reduced at the mucosal surface to provide ferrous iron for membrane transport into enterocytes.

Animals↗
PubMed1976

[Comparison of the metabolism of 2 injectable iron preparations (sorbitol iron and polymaltose iron) with the metabolism of transferrin and hemoglobin iron].

Iron distribution in the different organs and chemical compartments of the rat has been studied after intravenous injection of 59Fe-sorbitol (Jectofer-Astra) and 59Fe-polymaltose (Fer Hausmann Lucien) and compared with the metabolism of 59Fe bound to transferrin and to hemoglobin. Both parenteral iron preparations are utilized more slowly than Iron-transferrin. The speed of red cell incorporation of 59Fe from sorbitol is similar to the hemoglobin iron utilization (half incorporation in red cells: 4 to 5 days). Iron polymaltose is much more slowly utilized (half incorporation in the red cells: 13 to 15 days). One third of the 59Fe from sorbitol is eliminated in urine, the remaining iron being taken up to 60% by the liver and to 30% by the bone marrow. It is very quickly catabolized, since as early as the first hour after injection most of the 59Fe is bound to polymaltose till the 14th day. Between the third and fourth week 25% of the 59Fe from polymaltose is found in hemosiderin. These metabolic differences are also found in man: 59Fe from iron sorbitol is found in urine after injection, is mobilized by desferrioxamine after six days, and eliminated through dialysis membranes. On the other hand the 59Fe from polymaltose is slowly but completely utilized and not mobilized by desferrioxamine in the first week after injection. The data give the indications for use and the pharmacokinetics of two forms of parenteral iron and oral preparations in the treatment of iron deficiency.

Animals↗
PubMed1989

[Women and iron deficiency--a problem? Iron levels in a group of fertile Norwegian women and the bioavailability of 3 low-dose iron supplements in women with low iron stores].

Serum ferritin levels were determined in 170 healthy Norwegian women (18-48 y, median age 36 y) including 23 blood donors. Exhausted iron stores, defined by serum ferritin levels less than 17 micrograms/l, were found in 21.8% of the non-donors, and in 30.4% of the donors. Women with serum ferritin levels less than or equal to 20 micrograms/l participated in a bioavailability study. They were randomized to one of three groups and given one of three different low dose iron supplements (18-20 mg iron per day) for six months. One of the supplements contained heme iron and non-heme iron, the other two contained non-heme iron only. Mean serum ferritin increase was significant for two of the supplements, the one containing heme iron giving the best result. All the supplements resulted in a significant decrease in TIBC.

Adult↗
PubMed2005

Nanophase iron phosphate, iron arsenate, iron vanadate, and iron molybdate minerals synthesized within the protein cage of ferritin.

Nanoparticles of iron phosphate, iron arsenate, iron molybdate, and iron vanadate were synthesized within the 8 nm interior of ferritin. The synthesis involved reacting Fe(II) with ferritin in a buffered solution at pH 7.4 in the presence of phosphate, arsenate, vanadate, or molybdate. O2 was used as the oxidant to deposit the Fe(III) mineral inside ferritin. The rate of iron incorporation into ferritin was stimulated when oxo-anions were present. The simultaneous deposition of both iron and the oxo-anion was confirmed by elemental analysis and energy-dispersive X-ray analysis. The ferritin samples containing iron and one of the oxo-anions possessed different UV/vis spectra depending on the anion used during mineral formation. TEM analysis showed mineral cores with approximately 8 nm mineral particles consistent with the formation of mineral phases inside ferritin.

Arsenates↗
PubMed1984

Iron absorption in non-transfused iron loading anaemias: prediction of risk for iron loading, and response to iron chelation treatment, in beta thalassaemia intermedia and congenital sideroblastic anaemias.

A variable rate of iron loading, reaching toxic levels in some patients, was seen in a series of non-transfused patients with beta thalassaemia intermedia or sideroblastic anaemia. The degree of anaemia was a poor guide to the risk of iron overload. However the extent of erythroid hyperplasia, judged by ferrokinetic studies or more simply by bone marrow aspiration, was useful in predicting both the rate of iron loading and the need for iron chelation therapy.

Absorption↗
PubMed1993

Relation between bone marrow hemosiderin iron, serum iron status markers, and chemical and histochemical liver iron content in 82 patients with alcoholic and nonalcoholic hepatic disease.

Bone marrow hemosiderin iron was assessed in 48 patients with alcoholic, and in 34 patients with nonalcoholic liver disease (53 men, 29 women, median age 55 years, range 18-84) and correlated to serum (S)-iron status markers (iron, transferrin, ferritin), as well as to histochemical hepatocyte iron and chemical liver iron content. In a control group of 53 healthy subjects (23 men, 30 women, median age 28 years, range 18-90) marrow hemosiderin iron and iron status markers were evaluated as well. Among liver patients, the marrow iron grade was higher in men than in women (p = 0.03). Correlations were found between marrow iron and histochemical liver iron (rho = 0.38, p = 0.0001) as well as chemical liver iron (rho = 0.33, p = 0.01). Marrow iron was correlated to S-ferritin (rho = 0.53, p = 0.0001), mean red cell volume (rho = 0.34, p = 0.003), and S-transferrin (rho = -0.24, p = 0.02). Alcoholics had a higher marrow iron grade than nonalcoholics (p = 0.001) and controls (p = 0.0001). Among controls, the marrow iron grade was likewise higher in men than in women (p = 0.01). Correlations were found between marrow iron and ferritin (rho = 0.64, p = 0.0001), transferrin saturation (rho = 0.56, p = 0.001), transferrin (rho = 0.53, p = 0.001), S-iron (rho = 0.37, p = 0.01), and hemoglobin in women (rho = 0.38, p = 0.05). The results indicate that alcoholics either have increased marrow hemosiderin iron stores, or display a redistribution of iron in reticuloendothelial cells from soluble ferritin-bound iron to insoluble hemosiderin iron. Among patients with absent marrow hemosiderin iron, 81% had absent hepatocyte hemosiderin iron as well. Among patients with absent hepatocyte hemosiderin iron, 23% had absent and 77% normal or increased marrow hemosiderin iron. Therefore, in patients with iron depletion, assessment of marrow hemosiderin iron yields more relevant information of iron status than assessment of hepatocyte hemosiderin iron.

Adolescent↗
PubMed1995

Iron absorption from the whole diet. Relation to meal composition, iron requirements and iron stores.

OBJECTIVE: To validate a new method of measuring iron absorption from the whole diet over several days, to compare iron absorption from two types of diets and to relate iron absorption to iron requirements and iron stores. DESIGN: Iron absorption from two diets was studied in 21 healthy young women. All non-haem iron in all meals was labelled to the same specific activity with an extrinsic radio-labelled iron tracer. Haem iron absorption was calculated from the amount of haem iron and absorption from a reference dose of iron. RESULTS: Iron absorption was concordant with individual iron requirements measured from menstrual blood losses and body weights. Total iron absorption from one diet designed to be highly bioavailable, would cover iron requirements in about 94% of menstruating women. Iron absorption was reduced by half from a diet with less meat, more phytate and more calcium with main meals. This type of diet would cover iron requirements in only 65% of adult menstruating women. For both diets there was a marked reduction in iron absorption with increasing serum ferritin. Iron balance was not positive above a serum ferritin of about 60 micrograms/l. CONCLUSIONS: Bioavailability of dietary iron is a key factor in iron nutrition. A diet with much lean meat, ascorbic acid and a low phytate content can cover iron requirements in most non-pregnant women. The powerful control of iron absorption implies that dietary iron overload cannot develop in normal subjects, even with diets having high iron content or high bioavailability.

Adult↗
PubMed2003

[Iron status and effect of early iron supplementation on sub-clinical iron deficiency in rural school-age children from mountainous areas of Beijing].

OBJECTIVE: To understand iron nutritional status in school-age children, incidence of the sub-clinical iron deficiency (SID) and effect of iron supplementation on SID in the rural school-age children from mountainous areas of Beijing. METHODS: The dietary survey and food frequency questionnaire survey were conducted in 1,012 school children aged 7 - 13 at rural mountainous areas of Fangshan District, Beijing, and their blood samples were collected for analyzing biochemical indicators for iron nutrition. Two hundred and sixty-seven children with IDs (iron deficiency store) and IDE (iron deficiency erythropoiesis), based on screening criteria for iron-deficiency anemia, received an iron supplementation (NaFeEDTA) capsule (containing 60 mg iron element) weekly, and those with IDA (iron deficiency anemia) received NaFeEDTA capsule thrice weekly for nine weeks. Blood biochemical indicators for iron nutrition were determined repeatedly and compared with those before and after the intervention. RESULTS: The daily average intakes of energy, protein, iron and vitamin C in school children of all age groups reached the daily recommended criteria (> 85% of the RNIs), but the proportion of heme in dietary iron constitution was lower. The average blood biochemical indicators for iron nutrition were as follows: serum ferritin (SF) (50.83 +/- 33.09) micro g/L, free erythrocyte protoporphyrin (FEP) (489.44 +/- 219.61) micro g/L, hemoglobin (Hb) (130.57 +/- 10.82) g/L, and the ratio of FEP/Hb (3.83 +/- 1.96), respectively. Incidence of total iron deficiency in rural children was 26.5%, with proportions of iron deficiency (IDs), iron deficiency erythropoiesis (IDE), and iron deficiency anemia (IDA) of 15.5%, 7.1%, and 3.9% respectively. SID accounted for 85.4% of the total iron deficiency, which was 5.8 times as much as IDA. With iron supplementation for 9 weeks, the hematdogical index of iron increased significantly and returned to the normal level. CONCLUSIONS: The incidence of subclinical iron deficiency in the rural school-age children was insidious and should be attached more importance, which was helpful to its early recognition and intervention. Iron supplementation is important for children with SID to prevent and decrease the occurrence of IDA.

Adolescent↗
PubMed2000

Concentration of iron and distribution of iron and transferrin after experimental iron overload in rat tissues in vivo: study of the liver, the spleen, the central nervous system and other organs.

The purpose of this study was to estimate the iron concentration in the liver, spleen and brain of control rats and rats overloaded with iron and to determine the distribution of iron and of transferrin (TF). Iron was administered to Wistar rats by food supplemented with 3% carbonyl iron for 3 months, or intraperitoneally, or intraveneously as iron polymaltose for 4 months (total administered dose: 300 or 350 mg/rat, respectively). Iron concentration was estimated by atomic absorption spectrophotometry and iron- and TF-distribution histochemically and immunohistochemically, respectively. In control rats the organ with the highest iron content was the spleen, followed by the liver and brain. After iron loading the increase of iron in the liver was greater than that of the spleen; iron concentration in the brain did not change significantly. Distribution of iron in the liver was in Kupffer cells throughout the lobule and in hepatocytes at its periphery. No difference in the number of positive cells or staining intensity for TF was observed between control rats and iron overloaded animals in the liver or central nervous system (CNS); the spleen was negative for TF. Distribution of TF in the liver showed a centrilobular localisation in hepatocytes. TF reaction in the brain occurred in oligodendrocytes, vessel walls, choroid plexus epithelial cells and some neurons. In conclusion, experimental iron overload in rats leads to iron uptake mainly by reticuloendothelial (RE) cells and hepatocytes, indicating that hepatocytes are of particular importance for iron metabolism. Iron uptake by the brain was not significant, probably because the brain is protected against iron overload. Iron overload did not influence location and quantity of TF in the liver and CNS, whereas the visualisation of iron and TF did not coincide. This indicates that TF may have other functions beyond iron transport.

Animals↗
PubMed2001

Iron status of the free-living, elderly Framingham Heart Study cohort: an iron-replete population with a high prevalence of elevated iron stores.

BACKGROUND: Although iron deficiency occurs commonly in vulnerable groups of women of reproductive age, infants, and children, less is known about the iron nutriture of the elderly. OBJECTIVE: Our objective was to evaluate the iron status of a noninstitutionalized, elderly US population, with a particular focus on 2 concerns unique to the elderly: 1) potential confounding effects of chronic disease on iron measures and 2) increased occurrence of elevated iron stores. DESIGN: Multiple iron measures, including serum ferritin (SF), transferrin saturation, mean cell volume, and hemoglobin, were used to evaluate the prevalence of iron deficiency (ID), iron deficiency anemia (IDA), and other measures of iron nutriture in 1016 elderly white Americans aged 67-96 y from the Framingham Heart Study. "Diseased" subjects were defined as those with possible pathologically altered iron measures due to inflammation, infection, elevated liver enzymes, hereditary hemochromatosis, or cancer. The effect of altered iron status on various prevalence estimates was assessed. RESULTS: The elderly subjects had a low prevalence of ID (2.7%), IDA (1.2%), and depleted iron stores (3%; SF < 12 microg/L). In contrast, 12.9% had elevated iron stores (SF > 300 microg/L in men and SF > 200 microg/L in women), of which only 1% was attributable to chronic disease. The prevalence of ID, IDA, and depleted iron stores was unaffected by the presence of chronic disease. CONCLUSIONS: The Framingham Heart Study cohort is an iron-replete elderly population with a high prevalence of elevated iron stores in contrast with a low prevalence of iron deficiency, with insignificant effects of chronic disease on these iron status estimates. The likely liability in iron nutriture in free-living, elderly white Americans eating a Western diet is high iron stores, not iron deficiency.

Aged↗
PubMed1996

Exochelins of Mycobacterium tuberculosis remove iron from human iron-binding proteins and donate iron to mycobactins in the M. tuberculosis cell wall.

To multiply and cause disease in the host, Mycobacterium tuberculosis must acquire iron from the extracellular environment at sites of replication. To do so, the bacterium releases high-affinity iron-binding siderophores called exochelins. In previous studies, we have described the purification and characterization of the exochelin family of molecules. These molecules share a common core structure with another type of high-affinity iron-binding molecule located in the cell wall of M. tuberculosis: the mycobactins. The water-soluble exochelins differ from each other and from water insoluble mycobactins in polarity, which is dependent primarily upon the length and modifications of an alkyl side chain. In this study, we have investigated the capacity of purified exochelins to remove iron from host high-affinity iron-binding molecules, and to transfer iron to mycobactins. Purified desferri-exochelins rapidly removed iron from human transferrin, whether it was 95 or 40% iron saturated, its approximate percent saturation in human serum, and from human lactoferrin. Desferri-exochelins also removed iron, but at a slower rate, from the iron storage protein ferritin. Purified ferri-exochelins, but not iron transferrin, transferred iron to desferri-mycobactins in the cell wall of live bacteria. To explore the possibility that the transfer iron from exochelins to mycobactins was influenced by their polarity, we investigated the influence of polarity on the iron affinity of exochelins. Exochelins of different polarity exchanged iron equally with each other. This study supports the concept that exochelins acquire iron for M. tuberculosis by removing this element from host iron-binding proteins and transferring it to desferri-mycobactins in the cell wall of the bacterium. The finding that ferri-exochelins but not iron transferrin transfer iron to mycobactins in the cell wall underscores the importance of exochelins in iron acquisition. This study also shows that the variable alkyl side chain on the core structure of exochelins and mycobactins, the principal determinant of their polarity, has little or no influence on their iron affinity.

Carrier Proteins↗
PubMed2000

Overexpression of the ferritin iron-responsive element decreases the labile iron pool and abolishes the regulation of iron absorption by intestinal epithelial (Caco-2) cells.

Mammalian cells regulate iron levels tightly through the activity of iron-regulatory proteins (IRPs) that bind to RNA motifs called iron-responsive elements (IREs). When cells become iron-depleted, IRPs bind to IREs present in the mRNAs of ferritin and the transferrin receptor, resulting in diminished translation of the ferritin mRNA and increased translation of the transferrin receptor mRNA. Likewise, intestinal epithelial cells regulate iron absorption by a process that also depends on the intracellular levels of iron. Although intestinal epithelial cells have an active IRE/IRP system, it has not been proven that this system is involved in the regulation of iron absorption in these cells. In this study, we characterized the effect of overexpression of the ferritin IRE on iron absorption by Caco-2 cells, a model of intestinal epithelial cells. Cells overexpressing ferritin IRE had increased levels of ferritin, whereas the levels of the transferrin receptor were decreased. Iron absorption in IRE-transfected cells was deregulated: iron uptake from the apical medium was increased, but the capacity to retain this newly incorporated iron diminished. Cells overexpressing IRE were not able to control iron absorption as a function of intracellular iron, because both iron-deficient cells as well as iron-loaded cells absorbed similarly high levels of iron. The labile iron pool of IRE-transfected cell was extremely low. Likewise, the reduction of the labile iron pool in control cells resulted in cells having increased iron absorption. These results indicate that cells overexpressing IRE do not regulate iron absorption, an effect associated with decreased levels of the regulatory iron pool.

Caco-2 Cells↗
PubMed2004

IscA mediates iron delivery for assembly of iron-sulfur clusters in IscU under the limited accessible free iron conditions.

Increasing evidence suggests that IscS, a cysteine desulfurase, provides sulfur for assembly of transient iron-sulfur clusters in IscU. IscU appears to act as a scaffold and eventually transfers the assembled clusters to target proteins. However, the iron donor for the iron-sulfur cluster assembly largely remains elusive. Here we find that Escherichia coli IscU fails to assemble iron-sulfur clusters when the accessible "free" iron in solution is limited by an iron chelator sodium citrate. Remarkably, IscA, an iron-sulfur cluster assembly protein with an iron association constant of 3.0 x 10(19) m(-1), is able to overcome the iron limitation due to sodium citrate and deliver iron for the IscS-mediated iron-sulfur cluster assembly in IscU. Substitution of the invariant cysteine residues Cys-99 or Cys-101 in IscA with serine completely abolishes the iron binding activity of the protein. The IscA mutants that fail to bind iron are unable to mediate iron delivery for the iron-sulfur cluster assembly in IscU under the limited accessible "free" iron conditions. The results suggest that IscA is capable of recruiting intracellular iron and providing iron for the iron-sulfur cluster assembly in IscU in cells in which the accessible "free" iron content is probably restricted.

Carrier Proteins↗
PubMed2002

Iron absorption in breast-fed infants: effects of age, iron status, iron supplements, and complementary foods.

BACKGROUND: Iron supplements are often recommended for older breast-fed infants, but little is known about factors affecting iron absorption from human milk or supplements. OBJECTIVE: We investigated the effects of age, iron status, and iron intake on iron absorption in healthy, term, breast-fed infants. DESIGN: Twenty-five infants were randomly assigned to receive either 1) iron supplements (1 mg x kg(-1) x d(-1)) from 4 to 9 mo of age, 2) placebo from 4 to 6 mo and iron supplements from 6 to 9 mo, or 3) placebo from 4 to 9 mo. Infants were exclusively breast-fed to 6 mo and partially breast-fed to 9 mo of age. Iron absorption was assessed by giving (58)Fe with mother's milk at 6 and 9 mo. Blood samples were obtained at 4, 6, and 9 mo, and complementary food intake was recorded at 9 mo. RESULTS: At 6 mo, mean (+/-SD) fractional iron absorption from human milk was relatively low (16.4 +/- 11.4%), with no significant difference between iron-supplemented and unsupplemented infants. At 9 mo, iron absorption from human milk remained low in iron-supplemented infants (16.9 +/- 9.3%) but was higher (P = 0.01) in unsupplemented infants (36.7 +/- 18.9%). Unexpectedly, iron absorption at 9 mo was not correlated with iron status but was significantly correlated with intake of dietary iron, including supplemental iron. CONCLUSIONS: Changes in the regulation of iron absorption between 6 and 9 mo enhance the infant's ability to adapt to a low-iron diet and provide a mechanism by which some, but not all, infants avoid iron deficiency despite low iron intakes in late infancy.

Absorption↗
PubMed2007

Iron absorption is more closely related to iron status than to daily iron intake in 12- to 48-mo-old children.

Few studies have evaluated iron absorption in small children after the first year of life. Our objectives were to examine the relations among iron intake, iron absorption, and iron status in a group of healthy children. We studied 28 children, ages 12 to 48 mo, after a 7-d home adaptation to a diet representative of their usual daily mineral intake. A multi-tracer stable isotope study was performed to assess iron absorption both from a meal ((58)Fe) and from a reference iron dose ((57)Fe) given with ascorbic acid without a meal. Iron intake was 6.9 +/- 2.4 mg, approximately the 35th percentile of typical U.S. intakes. Absorption of (58)Fe was related to serum ferritin (r(2) = 0.319, P = 0.0018) and more so to reference dose iron absorption (r(2) = 0.653, P < 0.0001). Iron absorption was negatively correlated with zinc intake (r(2) = 0.090, P = 0.0049) but was not correlated with iron intake (P = 0.20). However, zinc intake was not correlated with measures of iron status, including reference dose iron absorption and serum ferritin (r(2) < 0.1, P > 0.25). Total absorbed iron was similar to needs estimated by the Institute of Medicine. We conclude that iron absorption in young children is more closely related to iron status than to iron intake. Reference dose iron absorption may be superior to serum ferritin as a surrogate measure for iron status in this age group. Although zinc intake may affect iron absorption from a meal, it does not appear to have a detectable effect on overall iron status in otherwise well-nourished children.

Administration, Oral↗
PubMed1999

Iron status and iron balance during pregnancy. A critical reappraisal of iron supplementation.

BACKGROUND: Iron supplementation in pregnancy is a controversial issue. The aim of this review was to summarize the results of relevant papers on this subject. METHODS: Placebo-controlled studies on iron treatment in pregnancy were identified from the Cochrane database. RESULTS: Among fertile women, 20% have iron reserves of >500 mg, which is the required minimum during pregnancy; 40% have iron stores of 100-500 mg, and 40% have virtually no iron stores. The demand for absorbed iron increases from 0.8 mg/day in early pregnancy to 7.5 mg/day in late pregnancy. Dietary iron intake in fertile women is median 9 mg/day, i.e. the majority of women have an intake below the estimated allowance of 12 18 mg/day. Iron absorption increases in pregnancy, but not enough to prevent iron deficiency anemia in 20%, of women not taking supplementary iron. Iron-treated pregnant women have greater iron reserves, higher hemoglobin levels, and a lower prevalence of iron deficiency anemia than placebo-treated women both in pregnancy as well as postpartum. Furthermore, children born to iron-treated mothers have higher serum ferritin levels than those born to placebo-treated mothers. An iron supplement of 65 mg/day from 20 weeks of gestation is adequate to prevent iron deficiency anemia. CONCLUSIONS: In order to avoid iron deficiency in pregnancy, prophylactic iron supplement should be considered. Iron supplements may be administered on a general or selective basis. The selective approach implies screening with serum ferritin in early pregnancy, in order to identify women who can manage without prophylactic iron.

Adult↗
PubMed1975

Bioavailability of trivalent iron in oral iron preparations. Therapeutic efficacy and iron absorption from simple ferric compounds and high- or low-molecular weight ferric hydroxide-carbohydrate complexes.

All available results from critical hemoglobin regeneration tests, postabsorption serum iron concentration studies, 59Fe erythrocyte incorporation and 59Fe whole-body retention measurements demonstrate that humans do absorb ferrous iron between 4 and 10 times (in the average about 5 times) better than ferric iron from therapeutic oral 50--250 mg iron doses. Ferrous sulfate iron is 3 to 4 times better available than the iron from ferric ammonium citrate or sulfate. Whereas 100 mg of ferrous sulfate iron/day are sufficient for an optimal oral compensation iron therapy and to produce initial hemoglobin regeneration rates of about 0.26 g/100 ml/day, 400 to 1000 mg of ferric iron/day are necessary for the same therapeutic effect because of the poor bioavailability of ferric iron. The ratio of the dose-absorption relationships for ferric and ferrous 59Fe was shown to decrease from 0.43 for a diagnostic 0.56 mg Fe dose to 0.21 for the therapeutic 50 mg Fe dose in subjects with normal iron stores. Absorption ratios of 0.65 for the 0.56 mg Fe dose and 0.26 for the 50 mg Fe dose were measured in subjects with depleted iron stores. At all dose levels the superior bioavailability of ferrous iron was demonstrable. A high-molecular weight ferric hydroxide-carbohydrate complex (MW similar to 30 000) was palatable but so poorly absorbed that is was practically without effect on hemoglobin regeneration even at a daily 300 mg Fe dose. Following several warnings such a useless commerecial oral iron preparation was finally withdrawn from the market. The iron from any high-molecular weight carbohydrate complex of ferric hydroxide has to be suspected to be poorly absorbed and therefore therapeutical useless, unless the opposite has been demonstrated with a reliable bioassay (59Fe absorption whole-body retention and hemoglobin regeneration test). A low-molecular weight so-called ferric hydroxide-fructose complex was shown to contain iron of more or less the same poor bioavailability as contained in ferric chloride since the iron from ferrous sulfate was about 5 times better absorable. The good absorption of ferrous sulfate iron was not further augmented by even very large oral doses of fructose since this carbohydrate did not improve the ferrous iron absorption at a fructose: Fe molar ratio of 106:1. Trivalent iron in simple compounds like ferric ammonium citrate or in low- and high-molecular weight carbohydrate complexes of ferric hydroxide is so poorly available for intestinal iron absorption in man that it cannot be used for a fast and reliable oral iron therapy with reasonably low doses as it can be easily practised with quick-lease preparations of ferrous sulfate at a 100 mg Fe2

Anemia, Hypochromic↗
PubMed2005

Thioredoxin reductase system mediates iron binding in IscA and iron delivery for the iron-sulfur cluster assembly in IscU.

IscA is a key member of the iron-sulfur cluster assembly machinery found in bacteria and eukaryotes. Previously, IscA was characterized as an alternative iron-sulfur cluster assembly scaffold, as purified IscA can host transient iron-sulfur clusters. However, recent studies indicated that IscA is an iron-binding protein that can provide iron for the iron-sulfur cluster assembly in a proposed scaffold IscU (Ding H., Clark, R. J., and Ding, B. (2004) J. Biol. Chem. 279, 37499-37504). To further elucidate the roles of IscA in the biogenesis of iron-sulfur clusters, we reevaluate the iron binding activity of IscA under physiologically relevant conditions. The results indicate that in the presence of the thioredoxin reductase system, Escherichia coli IscA binds iron with an iron association constant of 2.0 x 10(19) M(-1) in vitro. Whereas all three components (thioredoxin 1, thioredoxin reductase and NADPH) in the thioredoxin reductase system are essential for mediating the iron binding in IscA, only catalytic amounts of thioredoxin 1 and thioredoxin reductase are required. In contrast, IscU fails to bind iron in the presence of the thioredoxin reductase system, suggesting that the iron binding in IscA is specific. Nevertheless, the thioredoxin reductase system can promote the iron-sulfur cluster assembly in IscU in the presence of the iron-loaded IscA, cysteine desulfurase (IscS), and L-cysteine, demonstrating a physiologically relevant system for the biogenesis of iron-sulfur clusters. The results provide additional evidence for the hypothesis that IscA is capable of recruiting intracellular "free" iron and delivering the iron for the iron-sulfur cluster assembly in IscU.

Carrier Proteins↗