Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1979 Jul 15;182(1):117–125. doi: 10.1042/bj1820117

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

J P Milsom, R G Batey
PMCID: PMC1161240  PMID: 496901

Abstract

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.

Full text

PDF
117

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Awai M., Chipman B., Brown E. B. In vivo evidence for the functional heterogeneity of transferrin-bound iron. I. Studies in normal rats. J Lab Clin Med. 1975 May;85(5):769–784. [PubMed] [Google Scholar]
  2. BROWN E. B., ROTHER M. L. STUDIES OF THE MECHANISM OF IRON ABSORPTION. I. IRON UPTAKE BY THE NORMAL RAT. J Lab Clin Med. 1963 Sep;62:357–373. [PubMed] [Google Scholar]
  3. Bailey-Wood R., White G. P., Jacobs A. The use of Chang cells cultured in vitro for the investigation of cellular iron metabolism. Br J Exp Pathol. 1975 Aug;56(4):358–362. [PMC free article] [PubMed] [Google Scholar]
  4. Baker E., Morgan E. H. The kinetics of the interaction between rabbit transferrin and reticulocytes. Biochemistry. 1969 Mar;8(3):1133–1141. doi: 10.1021/bi00831a046. [DOI] [PubMed] [Google Scholar]
  5. Beamish M. R., Keay L., Okigaki T., Brown E. B. Uptake of transferrin-bound iron by rat cells in tissue culture. Br J Haematol. 1975 Dec;31(4):479–491. doi: 10.1111/j.1365-2141.1975.tb00883.x. [DOI] [PubMed] [Google Scholar]
  6. Drysdale J. W., Munro H. N. Regulation of synthesis and turnover of ferritin in rat liver. J Biol Chem. 1966 Aug 10;241(15):3630–3637. [PubMed] [Google Scholar]
  7. Ellis G., Goldberg D. M. Optimal conditions for the kinetic assay of serum glutamate dehydrogenase activity at 37 degrees C. Clin Chem. 1972 Jun;18(6):523–527. [PubMed] [Google Scholar]
  8. Fletcher J., Huehns E. R. Function of transferrin. Nature. 1968 Jun 29;218(5148):1211–1214. doi: 10.1038/2181211a0. [DOI] [PubMed] [Google Scholar]
  9. Fletcher J. The plasma clearance and liver uptake of iron from transferrin of low and high iron saturation. Clin Sci. 1971 Nov;41(5):395–402. doi: 10.1042/cs0410395. [DOI] [PubMed] [Google Scholar]
  10. Gardiner M. E., Morgan E. H. Transferrin and iron uptake by the liver in the rat. Aust J Exp Biol Med Sci. 1974 Oct;52(5):723–736. doi: 10.1038/icb.1974.72. [DOI] [PubMed] [Google Scholar]
  11. Harrison P. M. Ferritin: an iron-storage molecule. Semin Hematol. 1977 Jan;14(1):55–70. [PubMed] [Google Scholar]
  12. Hemmaplardh D., Morgan E. H. The role of endocytosis in transferrin uptake by reticulocytes and bone marrow cells. Br J Haematol. 1977 May;36(1):85–96. doi: 10.1111/j.1365-2141.1977.tb05758.x. [DOI] [PubMed] [Google Scholar]
  13. Huebers H., Huebers E., Forth W., Rummel W. Binding of iron to a non-ferritin protein in the mucosal cells of normal and iron-deficient rats during absorption. Life Sci I. 1971 Oct 15;10(20):1141–1148. doi: 10.1016/0024-3205(71)90274-8. [DOI] [PubMed] [Google Scholar]
  14. JANDL J. H., KATZ J. H. The plasma-to-cell cycle of transferrin. J Clin Invest. 1963 Mar;42:314–326. doi: 10.1172/JCI104718. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kuenzle C. C., Döbeli M. Insolubilized lactoperoxidase for the (125I)-labeling of proteins. Experientia. 1973;29(7):800–801. doi: 10.1007/BF01946294. [DOI] [PubMed] [Google Scholar]
  16. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  17. Lane R. S. Binding of transferrin and metal ions by suspensions of reticulocyte-rich rabbit blood. Biochim Biophys Acta. 1973 Aug 17;320(1):133–142. doi: 10.1016/0304-4165(73)90173-6. [DOI] [PubMed] [Google Scholar]
  18. Lloyd J. B. A study of permeability of lysosomes to amino acids and small peptides. Biochem J. 1971 Jan;121(2):245–248. doi: 10.1042/bj1210245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. MEGO J. L., MCQUEEN J. D. THE UPTAKE AND DEGRADATION OF INJECTED LABELED PROTEINS BY MOUSE-LIVER PARTICLES. Biochim Biophys Acta. 1965 Apr 12;100:136–143. doi: 10.1016/0304-4165(65)90436-8. [DOI] [PubMed] [Google Scholar]
  20. MORGAN E. H. THE INTERACTION BETWEEN RABBIT, HUMAN AND RAT TRANSFERRIN AND RETICULOCYTES. Br J Haematol. 1964 Oct;10:442–452. doi: 10.1111/j.1365-2141.1964.tb00721.x. [DOI] [PubMed] [Google Scholar]
  21. Mego J. L., McQueen J. D. Further studies on the degradation of injected [131-I] albumin by secondary lysosomes of mouse liver. Biochim Biophys Acta. 1965 Nov 15;111(1):166–173. doi: 10.1016/0304-4165(65)90483-6. [DOI] [PubMed] [Google Scholar]
  22. Milsom J. P., Batey R. G. Metabolism of transferrin-bound iron by the liver: a study in vivo. Biochem Soc Trans. 1978;6(5):966–968. doi: 10.1042/bst0060966. [DOI] [PubMed] [Google Scholar]
  23. Munro H. N., Linder M. C. Ferritin: structure, biosynthesis, and role in iron metabolism. Physiol Rev. 1978 Apr;58(2):317–396. doi: 10.1152/physrev.1978.58.2.317. [DOI] [PubMed] [Google Scholar]
  24. Seymour C. A., Peters T. J. Enzyme activities in human liver biopsies: assay methods and activities of some lysosomal and membrane-bound enzymes in control tissue and serum. Clin Sci Mol Med. 1977 Mar;52(3):229–239. doi: 10.1042/cs0520229. [DOI] [PubMed] [Google Scholar]
  25. Sullivan A. L., Grasso J. A., Weintraub L. R. Micropinocytosis of transferrin by developing red cells: an electron-microscopic study utilizing ferritin-conjugated transferrin and ferritin-conjugated antibodies to transferrin. Blood. 1976 Jan;47(1):133–143. [PubMed] [Google Scholar]
  26. Sullivan A. L., Weintraub L. R. Identification of 125I-labeled rat reticulocyte membrane proteins with affinity for transferrin. Blood. 1978 Aug;52(2):436–446. [PubMed] [Google Scholar]
  27. Sutton H. E., Karp G. W., Jr Adsorption of rivanol by potato starch in the isolation of transferrins. Biochim Biophys Acta. 1965 Aug 24;107(1):153–154. doi: 10.1016/0304-4165(65)90407-1. [DOI] [PubMed] [Google Scholar]
  28. Van Wyk C. P., Linder-Horowitz M., Munro H. N. Effect of iron loading on non-heme iron compounds in different liver cell populations. J Biol Chem. 1971 Feb 25;246(4):1025–1031. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES