Hepatic Iron Uptake Research Articles

Properties and hepatic metabolism of non-transferrin-bound iron.

These experiments have examined the physical properties and the hepatic uptake of non-transferrin-bound iron, a fraction found in the serum of untreated primary hemochromatosis patients. Ultrafiltration, polyacrylamide gel electrophoresis, and TLC have demonstrated the non-transferrin-bound iron complex to have a molecular weight less than 1000 and to be distinct from free iron and amino acid iron complexes. Hepatic iron uptake from serum containing non-transferrin-bound iron was significantly higher than from the same serum sample from which the abnormal iron had been removed. Non-transferrin-bound iron entering the liver was localized to the lysosomal fraction in the first hour and was subsequently incompletely incorporated into ferritin. The results demonstrated an abnormal uptake of this iron fraction by the liver and suggest that the abnormal serum fraction may contribute to tissue damage by entering the lysosomes.

A physiological model for hepatic metabolism of transferrin-bound iron.

Hepatic iron and transferrin uptake following intravenous injection of purified native rat transferrin has been studied in the rat. Livers were removed at varying time intervals postinjection and were fractionated by isopycnic density gradient centrifugation. Neither 59Fe or 125I (labeling transferrin) appeared in the lysosomal or mitochrondrial fractions at any stage up to 14 days. 59Fe first appears in the supernatant zone of the sucrose gradient and with increasing time postinjection passes through regions of increasing density. By 16 h 59Fe became established at a density of 1.10 g/cm3 and it was identified as ferritin. Ferritin persisted labeled with 59Fe for up to 14 days. The study suggests hepatic iron uptake does not involve endocytosis. Iron is incorporated into ferritin of increasing density. This model can be used for the study of iron metabolism in human biopsy samples.

The mechanism of hepatic iron uptake from native and denatured transferrin and its subcellular metabolism in the liver cell

Hepatic iron uptake and metabolism were studied by subcellular fractionation of rat liver homogenates after injection of rats with a purified preparation of either native or denatured rat transferrin labelled with 125I and 59Fe. (1) With native transferrin, hepatic 125I content was maximal 5 min after injection and then fell. Hepatic 59Fe content reached maximum by 16 h after injection and remained constant for 14 days. Neither label appeared in the mitochondrial or lysosomal fractions. 59Fe appeared first in the supernatant and, with time, was detectable as ferritin in fractions sedimented with increasingly lower g forces. (2) With denatured transferrin, hepatic content of both 125I and 59Fe reached maximum by 30 min. Both appeared initially in the lysosomal fraction. With time, they passed into the supernatant and 59Fe became incorporated into ferritin. The study suggests that hepatic iron uptake from native transferrin does not involve endocytosis. However, endocytosis of denatured transferrin does occur. After the uptake process, iron is gradually incorporated into ferritin molecules, which subsequently polymerize; there is no incorporation into other structures over 14 days.

Hepatic iron clearance from serum in treated hemochromatosis

Hepatic iron uptake from transferrin has been studied in 7 patients with treated hemochromatosis. When compared with a control group with similar serum iron and transferrin saturation the hemochromatotics had a significantly higher 4-hr iron uptake value. Uptake in the precirrhotic and cirrhotic hemochromatotics was not significantly different, suggesting the existence of a cellular abnormality of hepatic iron metabolism in this disease. The results provide an explanation for the development of siderosis in some patients with idiopathic hemochromatosis and a normal serum iron concentration.

The control of hepatic iron uptake: correlation with transferring synthesis.

The control of hepatic iron uptake was studied in the perfused liver isolated from rats subjected to nutritional iron deficiency. The total hepatic iron uptake and incorporation into ferritin was found to be higher in iron deficiency and during the 48 h of oral refeeding with iron than in the normal state. Specific incorporation of iron into feritin from a perfusate of normal transferrin iron saturation was enhanced in nutritional iron deficiency as compared to controls after 5 h of perfusion but not after 1 h, suggesting that increased uptake of iron from the perfusate may play a role in stimulating hepatic ferritin synthesis and assembly. This promotion of uptake into ferritin was inhibited by cycloheximide suggesting that enhanced incorporation of iron is dependent upon de novo synthesis of apoferritin. In control, nutritionally iron deficient and iron-refed rats there was a significant, direct correlation between the transferrin-iron saturation of the perfusate at physiological transferrin concentrations and total hepatic iron uptake after 5 h perfusion. A significant positive correlation was found between the hepatic total and ferritin iron uptake and the transferrin synthetic rate measured in the same liver. It is proposed that in the liver the negative feedback of iron supply on transferrin synthesis may be linked with a positive feedback on ferritin synthesis. The time-course of these reciprocal responses suggests a role for hepatic ferritin and/or a component of the non-haem, non-ferritin iron pool in the regulation of transferrin synthesis.

Hepatic Iron Uptake in Treated Haemochromatosis

Conference Abstract| September 01 1977 Hepatic Iron Uptake in Treated Haemochromatosis R. Batey; R. Batey 1Departments of Medicine and Haematology, Royal Free Hospital, and Department of Medical Physics, Hammersmith Hospital, London Search for other works by this author on: This Site PubMed Google Scholar J. Pettit; J. Pettit 1Departments of Medicine and Haematology, Royal Free Hospital, and Department of Medical Physics, Hammersmith Hospital, London Search for other works by this author on: This Site PubMed Google Scholar A. W. Nicholas; A. W. Nicholas 1Departments of Medicine and Haematology, Royal Free Hospital, and Department of Medical Physics, Hammersmith Hospital, London Search for other works by this author on: This Site PubMed Google Scholar S. Sherlock S. Sherlock 1Departments of Medicine and Haematology, Royal Free Hospital, and Department of Medical Physics, Hammersmith Hospital, London Search for other works by this author on: This Site PubMed Google Scholar Clin Sci Mol Med (1977) 53 (3): 14P. https://doi.org/10.1042/cs053014Pa Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Cite Icon Cite Get Permissions Citation R. Batey, J. Pettit, A. W. Nicholas, S. Sherlock; Hepatic Iron Uptake in Treated Haemochromatosis. Clin Sci Mol Med 1 September 1977; 53 (3): 14P. doi: https://doi.org/10.1042/cs053014Pa Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search Search Dropdown Menu toolbar search search input Search input auto suggest filter your search All ContentAll JournalsClinical Science Search Advanced Search This content is only available as a PDF. © 1977 The Biochemical Society and the Medical Research Society1977 Article PDF first page preview Close Modal You do not currently have access to this content.

Effect of Iron Saturation of Transferrin on Hepatic Iron Uptake: An in Vitro Study

Studies were performed to delineate the effect of percentage of saturation of transferrin and total iron concentration on the rate of uptake of iron by the perfused rat liver. Normal and iron-deficient rat livers were perfused with sera that contained varying concentrations of 59Fe-labeled iron and transferrin saturation. Varying the percentage of saturation of transferrin while maintaining a constant concentration of iron did not influence the hepatic uptake of iron. However, raising the concentration of iron in the perfusate while maintaining a constant saturation of transferrin did increase the uptake of iron by the liver. At similar concentrations of iron and transferrin saturation, iron-deficient livers took up greater amounts of iron than did normal livers. In our experiments, the hepatic uptake of transferrin-bound iron is determined by (1) the concentration of iron in perfusate and (2) the status of iron stores in the liver being perfused.

The effect of sex difference on iron exchange in the rat.

Summary.When compared with normal males, female Wistar rats have significantly higher serum iron levels, a higher rate of plasma iron turnover and a higher proportion of their plasma iron is diverted into non‐erythroid tissues. These difference are abolished by castration and reestablished by the supplementation of testosterone and oestrogen to castrated animals. The effect of sex hormones on iron handling is independent of their action on erythropoiesis, since in hypertransfused animals with complete inhibition of erythropoiesis the sex difference in serum iron levels and in hepatic iron uptake is maintained, The absolute rate of iron absorption is similar in both groups, but when the daily absorption of food iron is related to growth rate, it is considerably higher in females than in males (P< 0.001). The cumulative effect of a relatively higher iron absorption in females is the establishment of large iron stores which by virtue of their higher rate of exchange with transferrin contribute to their higher plasma iron turnover.