• Hepdicin exerts its biological function upon binding to the only known cellular iron exporter, ferroportin (SLC40A1), thereby leading to ferroportin internalization and degradation. (haematologica.org)
  • Within the phagocytes, iron is recycled through enzymatic degradation of heme and delivered via ferroportin into the circulation, accounting for approximately 90% of the daily iron needs. (haematologica.org)
  • 1 , 7 In addition, pro-and anti-inflammatory cytokines further contribute to iron retention within monocytes/macrophages by stimulating iron uptake pathways while inhibiting ferroportin transcription in these cells. (haematologica.org)
  • The hormone binds to its receptor ferroportin, the sole exporter of cellular iron into plasma. (ashpublications.org)
  • Ferroportin is prominently expressed in enterocytes, iron-recycling macrophages and hepatocytes. (ashpublications.org)
  • Hepcidin binding initiates the endocytosis and proteolysis of ferroportin and thereby decreases iron flow into plasma. (ashpublications.org)
  • Iron accumulates in cells that lack plasma membrane ferroportin, which leads to lower amounts of circulating iron available for erythropoiesis. (biomedcentral.com)
  • Hepc accomplishes this by triggering degradation of the only known cellular iron exporter ferroportin in the gut, macrophages, and liver. (ox.ac.uk)
  • Ferroportin disease (hemochromatosis type 4) is a recently recognized disorder of human iron metabolism, characterized by iron deposition in macrophages, including Kupffer cells. (intrinsiclifesciences.com)
  • Mutations in the gene encoding ferroportin 1, a cellular iron exporter, are responsible for this iron storage disease, inherited as an autosomal dominant trait. (intrinsiclifesciences.com)
  • In conclusion, the systemic iron burden in ferroportin disease is not a sufficient cause for chronic liver disease. (intrinsiclifesciences.com)
  • In patients with most, but not all, ferroportin mutations, retention of iron in macrophages of the liver and other organs may protect against damage to parenchymal cells. (intrinsiclifesciences.com)
  • Finally, macrophage iron storage in ferroportin disease is associated with elevated serum pro-hepcidin levels. (intrinsiclifesciences.com)
  • utations in the human gene encoding ferroportin 1 (FPN1/IREG-1/MTP-1/SLC40A1) are associated with an unusual iron overload syndrome, recently named hemochromatosis type 4 or ferroportin disease. (intrinsiclifesciences.com)
  • Hepcidin, which is expressed in the liver, heart, 16 and kidney, 17 is the key mediator of anemia of inflammation, 18,19 and synthetic hepcidin was shown to interact physically with ferroportin in a cellular overexpression system, causing internalization and degradation, and decreased export of iron. (intrinsiclifesciences.com)
  • Hepcidin inhibits the cellular efflux of iron by binding to and inducing the degradation of ferroportin (FPN) , the sole iron exporter in iron-transporting cells, thereby blocking iron flow into plasma. (diff.org)
  • Considering the tissue distribution of ferroportin, the hepcidin-ferroportin interaction explains the efferent arm of iron homeostasis because it can control the iron absorption in the duodenum, as well as the release of iron from macrophages and hepatocytes. (diff.org)
  • Effect of ferroportin Q248H polymorphism on iron status in African chi" by Ishmael Kasvosve, Zvenyika A.R. Gomo et al. (howard.edu)
  • Among these, the master regulator of iron homeostasis, hepcidin, appears to play a pivotal role. (haematologica.org)
  • Hepcidin is an anti-microbial peptide formed of 25 amino acids, which is produced mainly in the liver in response to iron overload or upon induction by pro-inflammatory stimuli, such as lipopolysaccharide or interleukin-6. (haematologica.org)
  • These changes are mediated predominantly by the polypeptide hepcidin, which acts to decrease the absorption and availability of iron, despite acute phase increases in iron-binding proteins, such as ferritin, which may suggest normal or increased iron stores. (biomedcentral.com)
  • However, assays, including hepcidin, offer the potential to identify iron restriction despite the presence of inflammation and may be coupled with promising therapeutic options to address issues including nosocomial infection and functional recovery for patients admitted to the ICU. (biomedcentral.com)
  • The advent of safe and effective intravenous iron preparations provides an opportunity to explore the potential benefits of treating patients diagnosed with functional iron deficiency in the ICU, when enteral iron is ineffective due to the actions of hepcidin. (biomedcentral.com)
  • The deficiency of hepcidin, the hormone that controls iron absorption and its tissue distribution, is the cause of iron overload in nearly all forms of hereditary hemochromatosis and in untransfused iron-loading anemias. (ashpublications.org)
  • Here we explore the feasibility of using minihepcidins for the prevention and treatment of iron overload in hepcidin-deficient mice. (ashpublications.org)
  • PR65 was administered by subcutaneous injection daily for 2 weeks to iron-depleted or iron-loaded hepcidin knockout mice. (ashpublications.org)
  • PR65 administration to hepcidin knockout mice with pre-existing iron overload had a more moderate effect and caused partial redistribution of iron from the liver to the spleen. (ashpublications.org)
  • Produced by the liver, hepcidin is a 25 amino acid peptide hormone that circulates in plasma and homeostatically controls body iron balance. (ashpublications.org)
  • 1 Iron levels in turn regulate hepcidin production: in healthy individuals, hepcidin production increases when plasma or tissue iron concentrations rise and decreases after iron depletion. (ashpublications.org)
  • In hereditary hemochromatoses (HH) types I-III, mutations in genes encoding hepcidin regulators, or hepcidin itself lead to diminished production of hepcidin thus decreasing the inhibitory effect of hepcidin on duodenal iron absorption and causing clinical iron overload. (ashpublications.org)
  • 3 Hepcidin deficiency and hyperabsorption of dietary iron are major factors not only in HH but also in iron overload associated with hereditary anemias caused by ineffective erythropoiesis. (ashpublications.org)
  • Hepcidin, an iron regulatory protein, is produced by hepatocytes and macrophages in response to proinflammatory stimuli. (biomedcentral.com)
  • Liver-Specific, but Not Retina-Specific, Hepcidin Knockout Causes Retinal Iron Accumulation and Degeneration. (ox.ac.uk)
  • The liver secretes hepcidin (Hepc) into the bloodstream to reduce blood iron levels. (ox.ac.uk)
  • To maximize intestinal iron absorption in cGKI -/- mice hepcidin mRNA levels are down regulated in the liver. (biomedcentral.com)
  • Hepcidin , a small peptide synthesized in the liver , controls extracellular iron by regulating its intestinal absorption, placental transport, recycling by macrophages, and release from stores. (diff.org)
  • When iron levels are high, molecules such as the hemochromatosis gene product ( HFE ), hemojuvelin ( HJV ) and transferrin receptor 2 ( TfR2 ) increase hepatic hepcidin expression. (diff.org)
  • It is suggested that hepcidin also decreases expression of proteins involved in intestinal iron absorption, such as duodenal cytochrome-b ( Dcytb ) and divalent metal transporter-1 ( DMT1 ), although the mechanism and extent of control is unknown. (diff.org)
  • Hepcidin induction by iron is homeostatic because increased plasma hepcidin would act to inhibit further intestinal iron absorption and iron release from stores. (diff.org)
  • However, the mechanism of hepcidin regulation by iron is turning out to be unexpectedly complex. (diff.org)
  • Although hepatocytes are the main sources of hepcidin, and the simplest model would place the iron sensor there (Fig 1), it is not certain that iron sensing takes place in hepatocytes. (diff.org)
  • The hepcidin mRNA lacks any stem-loop structures containing the consensus IRE motif for binding of iron-regulatory proteins. (diff.org)
  • Perhaps the best clue about hepcidin regulation by iron comes from the studies of genes involved in hereditary hemochromatosis. (diff.org)
  • Thus hepcidin levels decrease, its inhibitory effects diminish, and more iron is made available from the diet and from the storage pool in macrophages and hepatocytes. (diff.org)
  • Thus, Julia Chifman's research aims to understand the cause of iron dysregulation in breast cancer through the study of certain cellular signaling pathways that affect iron homeostasis. (american.edu)
  • Assistant Professor of Mathematics and Statistics Julia Chifman and her collaborators built a predictive mathematical model that connects four key cytosolic cellular signaling pathways in breast epithelial cells: the oncogenic pathway, the oxidative stress response pathway, the iron utilization pathway, and the iron homeostasis pathway. (american.edu)
  • namely, defects in the oncogenic pathway are noted to induce modifications in cellular iron homeostasis. (american.edu)
  • Through simulations, Chifman and her collaborators found that overexpression of Ras, a central species in the oncogenic pathway, led to a cancer phenotype in the iron homeostasis pathway. (american.edu)
  • Failure to maintain iron homeostasis early after a profound insult may result in an accumulation of highly reactive free iron, or non-transferrin bound iron, inflicting further oxidative stress on vulnerable organs or scavenged by invading microorganisms. (biomedcentral.com)
  • Here, we show that proper Mn homeostasis is critical for cellular growth of the major human respiratory pathogen Streptococcus pneumoniae. (indiana.edu)
  • Perturbations in Mn homeostasis genes, psaBCA, encoding the Mn importer, and mntE, encoding the Mn exporter, lead to Mn sensitivity during aerobiosis. (indiana.edu)
  • The cancer cell lines used autophagy to sustain iron homeostasis in contrast to other tumor types that relied on macropinocytosis . (blogshub.org)
  • Previous work had highlighted the role of ferritinophagy -a selective form of autophagy-and its role in iron homeostasis maintenance. (blogshub.org)
  • Different subcellular compartments are suggested to be linked through complex retrograde signaling networks to regulate cellular metal homeostasis. (frontiersin.org)
  • Moreover, modulation of the proteins involved in cellular metal homeostasis may help in the regulation of metabolism, adaptability to a diverse range of environmental conditions, and biofortification. (frontiersin.org)
  • This machinery is known as iron metabolism. (american.edu)
  • When iron metabolism ceases to function properly, the resulting iron excess or deficit can lead to serious faults in other cellular structures and regulatory systems. (american.edu)
  • Critical illness results in profound and characteristic changes to iron metabolism that are highly conserved from an evolutionary perspective. (biomedcentral.com)
  • Historically, the possibility of iron deficiency was largely unexplored in critically ill patients due to the confounding effects of acute inflammation on commonly available iron measures, the lack of safe and effective treatments and uncertainty as to the clinical significance of deranged iron metabolism. (biomedcentral.com)
  • These advances are timely as emerging data suggest that disordered iron metabolism is of substantial prognostic significance in critical illness. (biomedcentral.com)
  • The requirement for tight homeostatic control of iron metabolism is further demonstrated by population data from Norway, suggesting an association between severe iron deficiency and risk of bloodstream infection [ 5 ]. (biomedcentral.com)
  • Inflammation also alters iron metabolism. (biomedcentral.com)
  • Hentze MW, Muckenthaler MU, Galy B, Camaschella C: Two to tango: regulation of Mammalian iron metabolism. (biomedcentral.com)
  • The outcomes emphasized a critical link between autophagy, iron metabolism and mitochondrial function to drive the progression of pancreatic ductal adenocarcinoma. (blogshub.org)
  • It enhances cellular activity, the starting point of all nutritional metabolism. (franchiseapply.com)
  • Alteration of the balance in uptake, distribution, and/or storage of these minerals severely impairs cellular metabolism and significantly affects plant growth and development. (frontiersin.org)
  • Thus, any change in the metal profile of a cellular compartment significantly affects metabolism. (frontiersin.org)
  • Here, we review progress in the understanding of different subcellular metal transport components in plants and discuss the prospects of regulating cellular metabolism and strategies to develop biofortified crop plants. (frontiersin.org)
  • The differential diagnosis of iron accumulation in macrophages also includes the anemia of inflammation, in which anemia is associated with inappropriate retention of iron in macrophages and hepatocytes despite iron-restricted erythropoiesis. (intrinsiclifesciences.com)
  • The complex is then internalized and degraded, decreasing iron release from macrophages and hepatocytes and reducing intestinal iron uptake. (diff.org)
  • A major component of this regulation is the protein transferrin, which binds iron ions absorbed from the duodenum and carries it in the blood to cells. (wikipedia.org)
  • However, activation of heme oxygenase-1 (HO-1) can upregulate ferritin expression, which binds to ferrous iron and detoxifies its pro-oxidant effect. (encyclopedia.pub)
  • In particular, iron has the capability to donate and accept electrons, which is an extremely useful property for many biological processes. (american.edu)
  • To avoid iron toxicity, yet to deliver adequate amounts of iron for biological processes, life on Earth has evolved to have sophisticated machinery that regulates iron at both the systemic and the cellular levels. (american.edu)
  • 7 During inflammatory processes, however, the biological half-life of erythrocytes is reduced as a consequence of oxidative stress and lipid-peroxidation, thus promoting erythrophagocytosis and reducing iron recirculation. (haematologica.org)
  • However, by reducing the capacity of the body to access iron for vital processes, persistent functional iron deficiency can become harmful. (biomedcentral.com)
  • We propose that Mn-metalloenzymes are particularly susceptible to hyperactivation or mismetallation, suggesting the need for exquisite cellular control of Mn-dependent metabolic processes. (indiana.edu)
  • Iron (Fe), zinc (Zn), manganese (Mn), and copper (Cu) are essential micronutrient mineral elements for living organisms, as they regulate essential cellular processes, such as chlorophyll synthesis and photosynthesis (Fe, Cu, and Mn), respiration (Fe and Cu), and transcription (Zn). (frontiersin.org)
  • Heme oxygenases (HOs) act on heme degradation to produce carbon monoxide (CO), free iron, ferritin, and biliverdin. (encyclopedia.pub)
  • HOs are the key-limiting enzymes in heme degradation leading to carbon monoxide (CO), ferrous iron, and biliverdin products. (encyclopedia.pub)
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  • 12 FPN1 is a putative transmembrane iron channel implicated in the egress of iron from duodenal enterocytes, macrophages, hepatocytes, and placenta (reviewed in McKie and Barlow 13 ). (intrinsiclifesciences.com)
  • 4 This blocks the transfer of absorbed iron from the duodenal enterocyte into the circulation - an effect which can be aggravated by tumor necrosis factor (TNF)-α 5 - and, in parallel, causes retention of iron within macrophages and monocytes. (haematologica.org)
  • These faults are well studied and are known to cause dangerous medical conditions such as neurodegeneration, heart failure, iron-deficiency anemia, and even cancer. (american.edu)
  • Besides iron deficiency and ACD, metabolic disturbances and vitamin deficiencies as well as commonly used IBD drugs can aggravate anemia in IBD. (haematologica.org)
  • Therefore, IBD-associated anemia is the prototype of iron deficiency combined with ACD. (haematologica.org)
  • There are high quality data that intravenous iron, compared to either oral iron or no iron, significantly decreases anemia and red blood cell (RBC) transfusion requirement in hospitalized patients, albeit with a potential increased risk of infection [ 6 ]. (biomedcentral.com)
  • At high doses, PR65 treatment also caused anemia because of profound iron restriction. (ashpublications.org)
  • These data indicate that anemia and splengomegaly in cGKI-/- and cGKI rescue mice is caused by iron deficiency anemia due to intestinal blood loss and can be rescued by treatment with esomeprazol. (biomedcentral.com)
  • After uptake in human cells, iron storage is precisely regulated. (wikipedia.org)
  • Thus, regulating the uptake and cellular distribution of these minerals is extremely important for optimal cellular functioning and could lead to breeding crop plants with better adaptability to changing environments and may contribute to providing healthy food with improved mineral contents. (frontiersin.org)
  • They experimentally attenuated the succinate dehydrogenase complex iron sulfur subunit in mitochondria to limit the availability of the labile iron pool. (blogshub.org)
  • In this work, Mukhopadhyay and the team showed how the inhibition of autophagy reduced the assembly of iron-sulfur clusters to stabilize a variety of proteins, including those involved in the electron transfer chain , such as succinate dehydrogenase complex iron sulfur subunit B (SDHB). (blogshub.org)
  • 8 All these events lead to retention of iron within phagocytes and to the development of functional iron deficiency, meaning that although iron is abundant in the body the metal is not available for erythropoiesis. (haematologica.org)
  • Iron is required for erythropoiesis and is also essential for many other life-sustaining functions including deoxyribonucleic acid (DNA) and neurotransmitter synthesis, mitochondrial function and the innate immune response. (biomedcentral.com)
  • Intravenous iron therapies have largely been investigated in the context of erythropoiesis. (biomedcentral.com)
  • Impaired growth is a direct result of Mn toxicity and does not result from iron-mediated Fenton chemistry, since cells remain sensitive to Mn during anaerobiosis or when hydrogen peroxide biogenesis is significantly reduced. (indiana.edu)
  • Hemochromatosis is the abnormal accumulation of iron in parenchymal organs, leading to organ toxicity. (medscape.com)
  • Fe readily changes its oxidative state, which allows participation in cellular functions, and its regulation is extremely important to avoid cellular toxicity. (frontiersin.org)
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  • Possibly that point, British iron suppliers experienced employed huge amounts belonging to the iron imported faraway from Sweden in order to Russia you can actually capsule house supplies. (attractionlab.com)
  • They are also involved in the regulating of various cellular activities including growth, differentiation, inflammation, infection, ischemia, aging, and disease pathogenesis and progression [ 7 ] . (encyclopedia.pub)
  • High blood iron levels can occur in patients with hereditary hemochromatosis or result from use of iron supplements or multiple blood transfusions. (ox.ac.uk)
  • Hearth Technology is a large-scale maker specialized in production of Ductile iron Grooved coupling and fittings .We have 350 personnel, including 185 skilled technicians, fifteen senior engineers. (beamcoupling.com)
  • Iron acquisition poses a problem for aerobic organisms because ferric iron is poorly soluble near neutral pH. (wikipedia.org)
  • Thus, these organisms have developed means to absorb iron as complexes, sometimes taking up ferrous iron before oxidising it back to ferric iron. (wikipedia.org)
  • Perls Prussian blue tissue staining for ferric iron showed that PPI treatment rescues the iron deficiency in the spleen of cGKI -/- mice and normalized serum iron levels. (biomedcentral.com)
  • Upregulation of cellular HO-1 levels is signature of oxidative stress for its downstream effects particularly under pro-oxidative status. (encyclopedia.pub)
  • We previously demonstrated that systemic Hepc knockout (HepcKO) mice, which have high serum iron, develop retinal iron overload and degeneration. (ox.ac.uk)
  • In IBD, this scenario is typically associated with iron deficiency which is a consequence of recurrent bleeding episodes from ulcerated intestinal mucosa. (haematologica.org)
  • The combination of functional iron deficiency due to ACD and chronic blood loss is the most common finding in IBD. (haematologica.org)
  • Despite its importance in maintaining health, iron deficiency is the most common nutritional deficiency worldwide and many of the risk factors for iron deficiency are also risk factors for developing critical illness. (biomedcentral.com)
  • The result is that iron deficiency is likely to be over-represented in critically ill patients, with an estimated incidence of up to 40% at the time of intensive care unit (ICU) admission [ 1 ]. (biomedcentral.com)
  • The result is a state of functional iron deficiency. (biomedcentral.com)
  • In summary, the available evidence suggests that both iron deficiency and iron excess may be harmful for critically ill patients and that clinical assessment of iron status in the ICU is important and should include consideration of both possibilities. (biomedcentral.com)
  • cGKI mutant mice clearly suffer from iron deficiency due to decreased plasma iron levels and the lack of iron in the spleen and liver. (biomedcentral.com)
  • The oncogenic signaling pathway includes cellular species that regulate the growth, differentiation, and survival of cells. (american.edu)
  • Most patients are asymptomatic and are diagnosed when elevated serum iron levels are noted on a routine chemistry screening panel or when screening is performed because a relative is diagnosed with hemochromatosis. (medscape.com)
  • The import numbers have started to look astounding," India Cellular and Electronics Association (ICEA) said in a letter to the electronics and IT ministry. (indiatimes.com)
  • The most commonly known and studied bioinorganic iron compounds (biological iron molecules) are the heme proteins: examples are hemoglobin, myoglobin, and cytochrome P450. (wikipedia.org)
  • PR65 administration to iron-depleted mice prevented liver iron loading, decreased heart iron levels, and caused the expected iron retention in the spleen and duodenum. (ashpublications.org)
  • Liver-specific HepcKO mice had elevated blood and retinal pigment epithelium (RPE) iron levels and increased free (labile) iron levels in the retina, despite an intact blood-retinal barrier. (ox.ac.uk)
  • Despite a significant burden of iron, no features of chronic liver disease were found in affected members of the family, including individuals aged up to 80 years. (intrinsiclifesciences.com)
  • Impaired iron export from macro-phages in patients with mutations in the FPN1 gene has been proposed as the explanation for the accumulation of iron that occurs in organs containing abundant macro-phages such as the liver, spleen, and bone marrow. (intrinsiclifesciences.com)
  • Orthotopic liver transplantation is the only therapeutic option when end-stage liver disease progresses despite iron-reduction therapy. (medscape.com)
  • Sarms netherlands, sarms wat is het Thus, if any of our readers are thinking about trying cardarine, we advise to get your liver enzymes tested, to better understand the condition of this organ before any potential cellular proliferation occurs. (cuneyttugrul.org)
  • 3,8,10,11 Deletion of this amino acid causes loss of function and when studied in vitro causes accumulation of iron in cultured cells. (intrinsiclifesciences.com)
  • 12 In addition, the immunity-driven down-regulation of erythropoietin receptors on erythroid progenitor cells and the limited availability of iron for heme biosynthesis negatively affect the biological functions of erythropoetin. (haematologica.org)
  • Mn-stressed cells accumulate iron and copper, in addition to Mn. (indiana.edu)
  • specification of the zinc ore from kogi state of nigeria copper ore in kogi sulfides and oxides of metals such as zinc, copper, nickel, agbaja mine is a shallow, flat-lying channel iron ore deposit located in kogi state, nigeria. (solarordinances.eu)
  • As one of the leading cardriveshaft manufacturers and exporters, we supply cardriveshaft and many other products for cluster cardriveshaft. (cardriveshaft.com)
  • Consistent with its function as lactate and proton exporter, MCT4 expression levels correlated inversely with extracellular pH and proportionally with extracellular lactate concentrations. (hindawi.com)
  • Cellular signaling pathways are networks of genes, proteins, enzymes, cytokines, and other cellular species that "communicate" in order to govern the basic functions of cells. (american.edu)
  • The changes in body iron distribution are caused by cytokines and acute phase proteins. (haematologica.org)
  • The storage and distribution of these minerals in various cellular organelles is strictly regulated to ensure optimal metabolic rates. (frontiersin.org)
  • Our study demonstrates that minihepcidins could be beneficial in iron overload disorders either used alone for prevention or possibly as adjunctive therapy with phlebotomy or chelation. (ashpublications.org)
  • The goal of therapy in patients with iron overload disorders is to remove the iron before it can produce irreversible parenchymal damage. (medscape.com)
  • Cellular iron levels and iron associated proteins are differentially expressed in many cancers, and recently, it was reported that high expression levels of iron importer and low levels of iron exporter were associated with a poor prognosis in breast cancer patients. (american.edu)
  • However, it was unclear whether this is caused by high blood iron levels or, alternatively, retinal iron influx that would normally be regulated by retina-produced Hepc. (ox.ac.uk)
  • In contrast, there was no change in retinal or RPE iron levels or degeneration in the retina-specific HepcKO mice. (ox.ac.uk)
  • These data indicate that high blood iron levels can lead to retinal iron accumulation and degeneration. (ox.ac.uk)
  • Our results suggest that high blood iron levels may cause or exacerbate retinal disease. (ox.ac.uk)
  • Various genes regulating cellular and subcellular metal distribution have been identified and characterized. (frontiersin.org)
  • Some examples of iron metalloproteins are ferritin and rubredoxin. (wikipedia.org)
  • These results were confirmed by western blot analysis for the iron storage protein ferritin light chain. (biomedcentral.com)
  • 6 The latter effect is of major importance, because macrophages are involved in the re-utilization of iron from senescent red blood cells which are taken up via erythrophagocytosis. (haematologica.org)
  • The biologists noted how cancer-associated fibroblasts provided bioavailable iron to pancreatic cancer cells to resist the ablation of autophagy. (blogshub.org)
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  • Iron is an important biological element. (wikipedia.org)
  • The iron-sulfur clusters are pervasive and include nitrogenase, the enzymes responsible for biological nitrogen fixation. (wikipedia.org)
  • In the schema of our project, our team sought two central goals: to increase the biological accuracy of the model through the addition of cellular species and intra-pathway connections to the oncogenic pathway, and to conduct new simulations using the updated oncogenic pathway. (american.edu)
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  • Fe participates in cellular respiration, synthesis, and stabilization of chlorophyll, photosynthetic electron transport, and various other metabolic functions ( Grotz and Guerinot, 2006 ). (frontiersin.org)
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