Imported ferrous Fe (II) ion have two pathways of modulation. After this, reduced ferrous Fe (II) ion is transported into gastrointestinal enterocytes by DMT-1. Luminal ferric Fe (III) ion from food intake is reduced to ferrous Fe (II) ion by DcytB in apical site of duodenal epithelia.
However, when stored, ferrous Fe (II) iron cannot be exported to blood vessels for various reasons and it accumulates in cells and organs, leading to iron overload (also known as hemochromatosis) in susceptible tissues, including the gut and liver ( Figure 1).ĭietary iron metabolism in gut. Exported ferrous Fe (II) ions are oxidized to ferric Fe (III) ion by HEPH and the oxidized ferric Fe (III) ion in a complex with transferrin is delivered via blood circulation to the target organs, such as the bone marrow for erythrocytosis, or liver for storage. However, the stored irons can be released from enterocytes, which is facilitated by ferroportin (FPN, an iron transporter) and a ferroxidase such as hephaestin (HEPH) or ceruloplasmin on the basolateral membrane of duodenal enterocyte in response to signals from the deficient organs, including bone marrow.
Imported ferrous Fe (II) ions need to be intracellularly stored by binding to ferritin, due to the toxicity of the free form. Another is divalent metal transporter-1 (DMT-1), which transports divalent metal ions into cells as the name implicates. One is duodenal cytochrome B (DcytB), which can reduce ferric Fe (III) ion to ferrous Fe (II) ion for transporting into the enterocytes. In response to various cues, including iron deficiency in the body, dietary iron ions can be absorbed in the apical site of duodenal enterocyte by two types of membrane proteins. Iron is an essential metal nutrient required for all living organisms. Introduction: Regulation of Dietary Iron Metabolism All of this evidence provides crucial insights into comprehensive clinical or nutritional interventions for hemochromatosis.ġ. Thus, the crosstalk between nutrients and genes would verify the complex procedures in the clinical outcomes of secondary hemochromatosis and chronic complications, such as malignancy. Moreover, the mutations in these sentineling pathway-linked genes increase susceptibility to secondary hemochromatosis. Although the mechanistic association to diet-linked etiologies can be complicated, the stress sentinels are pivotally involved in the pathological processes of secondary hemochromatosis in response to iron excess and other external stresses. The present review addresses diet-linked etiologies of hemochromatosis and their pathogenesis in the network of genes and nutrients. Although hereditary hemochromatosis is associated with the mutation of genes involved in iron transport and metabolism, secondary hemochromatosis is due to external factors, such as intended or unintended iron overload, hemolysis-linked iron exposure or other stress-impaired iron metabolism.