Iron is an essential trace metal in the human diet due to its obligate role in a number of metabolic processes. In the diet, iron is present in a number of different forms, generally described as haem （from haemoglob...Iron is an essential trace metal in the human diet due to its obligate role in a number of metabolic processes. In the diet, iron is present in a number of different forms, generally described as haem （from haemoglobin and myoglobin in animal tissue） and non-haem iron （including ferric oxides and salts, ferritin and lactoferrin）. This review describes the molecular mechanisms that co-ordinate the absorption of iron from the diet and its release into the circulation. While many components of the iron transport pathway have been elucidated, a number of key issues still remain to be resolved. Future work in this area will provide a clearer picture regarding the transcellular flux of iron and its regulation by dietary and humoral factors.展开更多
The human body requires about 1-2 mg of iron per day for its normal functioning, and dietary iron is the only source for this essential metal. Since humans do not possess a mechanism for the active excretion of iron, ...The human body requires about 1-2 mg of iron per day for its normal functioning, and dietary iron is the only source for this essential metal. Since humans do not possess a mechanism for the active excretion of iron, the amount of iron in the body is determined by the amount absorbed across the proximal small intestine and, consequently, intestinal iron absorption is a highly regulated process. In recent years, the liver has emerged as a central regulator of both iron absorption and iron release from other tissues. It achieves this by secreting a peptide hormone called hepcidin that acts on the small intestinal epithelium and other cells to limit iron delivery to the plasma. Hepcidin itself is regulated in response to various systemic stimuli including variations in body iron stores, the rate of erythropoiesis, inflammation and hypoxia, the same stimuli that have been known for many years to modulate iron absorption. This review will summarize recent findings on the role played by the liver and hepcidin in the regulation of body iron absorption.展开更多
AIM： To understand the interactions between iron and zinc during absorption in iron- and zinc-deficient rats, and their consequences on intestinal oxidant-antioxidant balance. METHODS： Twenty-four weanling Wistar-Ky...AIM： To understand the interactions between iron and zinc during absorption in iron- and zinc-deficient rats, and their consequences on intestinal oxidant-antioxidant balance. METHODS： Twenty-four weanling Wistar-Kyoto rats fed an iron- and zinc-deficient diet （〈 6.5 mg Fe and 4.0 mg Zn/kg diet） for 4 wk were randomly divided into three groups （n = 8, each） and orally gavaged with 4 mg iron, 3.3 mg zinc, or 4 mg iron ＋ 3.3 mg zinc for 2 wk. At the last day of repletion, 3 h before the animals were sacrificed, they received either 37 mBq of SSFe or ^65Zn, to study their localization in the intestine, using microautoradiography. Hemoglobin, iron and zinc content in plasma and liver were measured as indicators of iron and zinc status. Duodenal sections were used for immunochemical staining of ferritin and metallothionein. Duodenal homogenates （mitochondrial and cytosolic fractions）, were used to assess aconitase activity, oxidative stress, functional integrity and the response of antioxidant enzymes. RESULTS： Concurrent repletion of iron- and zinc-deficient rats showed reduced localization of these minerals compared to rats that were teated with iron or zinc alone; these data provide evidence for antagonistic interactions. This resulted in reduced formation of lipid and protein oxidation products and better functional integrity of the intestinal mucosa. Further, combined repletion lowered iron-associated aconitase activity and ferritin expression, but significantly elevated metallothionein and glutathione levels in the intestinal mucosa. The mechanism of interactions during combined supplementation and its subsequent effects appeared to be due to through modulation of cytosolic aconitase, which in turn influenced the labile iron pool and metallothionein levels, and hence reduced intestinal oxidative damage.CONCLUSION： Concurrent administration of iron and zinc corrects iron and zinc deficiency, and also reduces the intestinal oxidative damage associated with iron supplementation.展开更多
AIM: To elucidate the sequential transfer of iron amongst ferritin, transferrin and transferrin receptor under various iron status conditions. METHODS: Incorporation of 59Fe into mucosal and luminal proteins was carri...AIM: To elucidate the sequential transfer of iron amongst ferritin, transferrin and transferrin receptor under various iron status conditions. METHODS: Incorporation of 59Fe into mucosal and luminal proteins was carried out in control WKY rats. The sequential transfer of iron amongst ferritin, transferrin and transferrin receptor was carried out in iron deficient, control and iron overloaded rats. The duodenal proteins were subjected to immunoprecipitation and quantitation by specific ELISA and in situ localization by microautoradiography and immunohistochemistry in tandem duodenal sections. Human duodenal biopsy (n = 36) collected from subjects with differing iron status were also stained for these proteins. RESULTS: Ferritin was identified as the major protein that incorporated iron in a time-dependent manner in the duodenal mucosa. The concentration of mucosal ferritin was significantly higher in the iron excess group compared to control, iron deficient groups (731.5 ± 191.96 vs 308.3 ± 123.36, 731.5 ± 191.96 vs 256.0 ± 1.19, P < 0.005), while that of luminal transferrin which was significantly higher than the mucosal did not differ among the groups (10.9 ± 7.6 vs 0.87 ± 0.79, 11.1 ± 10.3 vs 0.80 ± 1.20, 6.8 ± 4.7 vs 0.61 ± 0.63, P < 0.001). In situ grading of proteins and iron, and their superimposition, suggested the occurrence of a sequential transfer of iron. This was demonstrated to occur through the initial binding of iron to luminal transferrin then to absorptive cell surface transferrin receptors. The staining intensity of these proteins variedaccording to the iron nutrition in humans, with intense staining of transferrin receptor observed in iron deficient subjects. CONCLUSION: It is concluded that the intestine takes up iron through a sequential transfer involving interaction of luminal transferrin, transferrin-transferrin receptor and ferritin.展开更多
文摘Iron is an essential trace metal in the human diet due to its obligate role in a number of metabolic processes. In the diet, iron is present in a number of different forms, generally described as haem （from haemoglobin and myoglobin in animal tissue） and non-haem iron （including ferric oxides and salts, ferritin and lactoferrin）. This review describes the molecular mechanisms that co-ordinate the absorption of iron from the diet and its release into the circulation. While many components of the iron transport pathway have been elucidated, a number of key issues still remain to be resolved. Future work in this area will provide a clearer picture regarding the transcellular flux of iron and its regulation by dietary and humoral factors.
文摘The human body requires about 1-2 mg of iron per day for its normal functioning, and dietary iron is the only source for this essential metal. Since humans do not possess a mechanism for the active excretion of iron, the amount of iron in the body is determined by the amount absorbed across the proximal small intestine and, consequently, intestinal iron absorption is a highly regulated process. In recent years, the liver has emerged as a central regulator of both iron absorption and iron release from other tissues. It achieves this by secreting a peptide hormone called hepcidin that acts on the small intestinal epithelium and other cells to limit iron delivery to the plasma. Hepcidin itself is regulated in response to various systemic stimuli including variations in body iron stores, the rate of erythropoiesis, inflammation and hypoxia, the same stimuli that have been known for many years to modulate iron absorption. This review will summarize recent findings on the role played by the liver and hepcidin in the regulation of body iron absorption.
文摘AIM： To understand the interactions between iron and zinc during absorption in iron- and zinc-deficient rats, and their consequences on intestinal oxidant-antioxidant balance. METHODS： Twenty-four weanling Wistar-Kyoto rats fed an iron- and zinc-deficient diet （〈 6.5 mg Fe and 4.0 mg Zn/kg diet） for 4 wk were randomly divided into three groups （n = 8, each） and orally gavaged with 4 mg iron, 3.3 mg zinc, or 4 mg iron ＋ 3.3 mg zinc for 2 wk. At the last day of repletion, 3 h before the animals were sacrificed, they received either 37 mBq of SSFe or ^65Zn, to study their localization in the intestine, using microautoradiography. Hemoglobin, iron and zinc content in plasma and liver were measured as indicators of iron and zinc status. Duodenal sections were used for immunochemical staining of ferritin and metallothionein. Duodenal homogenates （mitochondrial and cytosolic fractions）, were used to assess aconitase activity, oxidative stress, functional integrity and the response of antioxidant enzymes. RESULTS： Concurrent repletion of iron- and zinc-deficient rats showed reduced localization of these minerals compared to rats that were teated with iron or zinc alone; these data provide evidence for antagonistic interactions. This resulted in reduced formation of lipid and protein oxidation products and better functional integrity of the intestinal mucosa. Further, combined repletion lowered iron-associated aconitase activity and ferritin expression, but significantly elevated metallothionein and glutathione levels in the intestinal mucosa. The mechanism of interactions during combined supplementation and its subsequent effects appeared to be due to through modulation of cytosolic aconitase, which in turn influenced the labile iron pool and metallothionein levels, and hence reduced intestinal oxidative damage.CONCLUSION： Concurrent administration of iron and zinc corrects iron and zinc deficiency, and also reduces the intestinal oxidative damage associated with iron supplementation.
基金Supported by Council of Scientific and Industrial research, India: schemes no (812) 93EMR11 to KMN
文摘AIM: To elucidate the sequential transfer of iron amongst ferritin, transferrin and transferrin receptor under various iron status conditions. METHODS: Incorporation of 59Fe into mucosal and luminal proteins was carried out in control WKY rats. The sequential transfer of iron amongst ferritin, transferrin and transferrin receptor was carried out in iron deficient, control and iron overloaded rats. The duodenal proteins were subjected to immunoprecipitation and quantitation by specific ELISA and in situ localization by microautoradiography and immunohistochemistry in tandem duodenal sections. Human duodenal biopsy (n = 36) collected from subjects with differing iron status were also stained for these proteins. RESULTS: Ferritin was identified as the major protein that incorporated iron in a time-dependent manner in the duodenal mucosa. The concentration of mucosal ferritin was significantly higher in the iron excess group compared to control, iron deficient groups (731.5 ± 191.96 vs 308.3 ± 123.36, 731.5 ± 191.96 vs 256.0 ± 1.19, P < 0.005), while that of luminal transferrin which was significantly higher than the mucosal did not differ among the groups (10.9 ± 7.6 vs 0.87 ± 0.79, 11.1 ± 10.3 vs 0.80 ± 1.20, 6.8 ± 4.7 vs 0.61 ± 0.63, P < 0.001). In situ grading of proteins and iron, and their superimposition, suggested the occurrence of a sequential transfer of iron. This was demonstrated to occur through the initial binding of iron to luminal transferrin then to absorptive cell surface transferrin receptors. The staining intensity of these proteins variedaccording to the iron nutrition in humans, with intense staining of transferrin receptor observed in iron deficient subjects. CONCLUSION: It is concluded that the intestine takes up iron through a sequential transfer involving interaction of luminal transferrin, transferrin-transferrin receptor and ferritin.
