Transcobalamins: Vitamin B12 Transport

  • Samuel Natelson
  • Ethan A. Natelson


In Volume 2 of this series, the transcobalamines were introduced, in connection with vitamin B12 function and transport (pp. 520–525). Here, a brief review will be given of this problem and of the develop­ments which have taken place since this subject was discussed in Volume 2.


Intrinsic Factor Polycythemia Vera Pernicious Anemia Megaloblastic Anemia Human Intrinsic Factor 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Selected Reading

  1. Zayalak, B. I., and Friedrich, W., Eds., Vitamin B-Twelve, Walter DeGruyter, Hawthorne, New York (1979).Google Scholar
  2. Babior, B. M., and Krouwer, J. S., The mechanism of adenosylcobalamin reactions, CRC Crit. Rev. Biochem. 6: 35–102 (1979).CrossRefGoogle Scholar
  3. Fernandes-Costa, F., et al., Role of serum folate binders in the delivery of folate to the fetus, Br. J. Haematol. 41: 335–342 (1979).CrossRefGoogle Scholar
  4. Carmel, R., Vitamin B12 binding proteins in serum and plasma in various disorders, Am. J. Clin. Pathol. 69: 319–325 (1978).Google Scholar
  5. Nexo, E., Transcobalamin I and other human R-binders: Purification, structural, spectral and physiological studies, Scand. J. Haematol. 20: 221–236 (1978).CrossRefGoogle Scholar
  6. Allen, R. H., Vitamin B12 binding proteins in human plasma, Prog. Clin. Biol. Res. 3: 357–375 (1976).Google Scholar
  7. Stenman, U. H., Intrinsic factor and the vitamin B12 binding proteins, Clin. Haematol. 5: 472–495 (1976).Google Scholar
  8. Hall, C. A., The carriers of native vitamin B12 in normal human serum, Clin. Sci. Mol. Med. 53: 453–457 (1977).Google Scholar
  9. Kass, L., Pernicious Anemia, Saunders, Philadelphia (1976).Google Scholar


  1. 1.
    Grasbeck, R., Simons, K., and Sinkkonen, I., Isolation of intrinsic factor and its probable degradation product, as their vitamin B12 complexes, from human gastric juice, Biophys. Biochim. Acta 127: 47–58 (1966).CrossRefGoogle Scholar
  2. 2.
    Allen, R. H., and Majerus, P. W., Isolation of vitamin B12-binding proteins using affinity chromatography. I. Preparation and properties of vitamin B12-Sepharose, J. Biol. Chem. 247: 7695–7701 (1972).Google Scholar
  3. 3.
    Allen, R. H., Human vitamin B12 transport proteins, in Progress in Hematology, IX, E. B. Brown, Ed., Grune and Stratton, New York (1975), pp. 57–84.Google Scholar
  4. 4.
    Bloomfield, F. J., and Scott, J. M., Identification of a new vitamin B12 binder (transcobalamin III) in normal human serum, Br. J. Haematol. 22: 33–42 (1972).CrossRefGoogle Scholar
  5. 5.
    Allen, R. H., Vitamin B12 binding proteins in human plasma, Prog. Clin. Biol. Res. 3: 357–375 (1976) .Google Scholar
  6. 6.
    Burger, R. L., Mehlman, C. S., and Allen, R. H., Human plasma R-type vitamin B12 binding proteins: Isolation and characterization of transcobalamin I, transcobalamin III, and the normal granulocyte vitamin B12 binding protein, J. Biol. Chem. 250: 7700–7713 (1975).Google Scholar
  7. 7.
    Nexe, E., Transcobalamin I and other human R-binders: Purification, structural, spectral and physiological studies, Scand. J. Haematol. 20: 221–236 (1978).CrossRefGoogle Scholar
  8. 8.
    Thomsen, J., Bucher, D., Brunfeldt, K., Nexe, E., and Olesen, H., An improved procedure for automated Edman degradation used for the determination of the N-terminal amino acid sequence of human transcobalamin I and human intrinsic factor, Eur. J. Biochem. 69: 87–96 (1976).CrossRefGoogle Scholar
  9. 9.
    Olesen, H., Nexe, E., Lous, P., Thomsen, J., and Bucher, D., Amino terminal sequence of human intrinsic factor, Scand. J. Lab. Invest. 36: 527–529 (1976).CrossRefGoogle Scholar
  10. 10.
    Nexe, E., Olesen, H., Bucher, D., and Thomsen, J., Purification and characterization of rabbit transcobalamin II, Biochim. Biophys. Acta 494: 395–402 (1977).Google Scholar
  11. 11.
    Marcoulis, G., Salonen, E-M., and Grasbaek, R., Porcine serum cobalophilin and transcobalamin: Identification, isolation and properties including electrofocusing patterns, Biochim. Biophys. Acta 534: 48–57 (1978).Google Scholar
  12. 12.
    Daiger, S. P., Labowe, M. L., Parsons, M., Wang, L., and Cavalli-Sforza, L. L., Detection of genetic variation with radioactive ligands. III. Genetic polymorphism of transcobalamin II in human plasma, Am. J. Hum. Genet. 30: 202–214 (1978).Google Scholar
  13. 13.
    Chanarin, I., Muir, M., Hughes, A., and Hoffbrand, A. V., Evidence for intestinal origin of transcobalamin II during vitamin B12 absorption, Br. Med. J. 1: 1453–1455 (1978).CrossRefGoogle Scholar
  14. 14.
    Nexe, E., and Andersen, J., Unsaturated and cobalamin saturated transcobalamin I and II in normal human plasma, Scand. J. Clin. Lab. Invest. 37: 723–728 (1977).CrossRefGoogle Scholar
  15. 15.
    Hall, C. A., The carriers of native B12 in normal human serum, Clin. Sci. Mol. Med. 53: 453–457 (1977).Google Scholar
  16. 16.
    Benson, R. E., Rappazzo, M. E., and Hall, C. A., Late transport of vitamin B12 by transcobalamin II, J. Lab. Clin. Med. 80: 488–495 (1972).Google Scholar
  17. 17.
    Horn, B. L., and Olesen, H. A., Plasma clearance of 57cobalt-labeled vitamin B12 bound in vitro to transcobalamin I and II, Scand. J. Clin. Lab. Invest. 23: 201–211 (1969).CrossRefGoogle Scholar
  18. 18.
    Youngdahl-Turner, P., and Rosenberg, L. E., Binding and uptake of transcobalamin II by human fibroblasts, J. Clin. Invest. 61: 133–141 (1978).CrossRefGoogle Scholar
  19. 19.
    Hall, C. A., and Green, P. D., Competition between apo and hobo transcobalamin II (TC-II) for the TC-II mediated uptake process, Proc. Soc. Exp. Biol. Med. 158: 206–209 (1978).Google Scholar
  20. 20.
    Hitzig, W. H., and Kenny, A. B., The role of vitamin B12 and its transport globulins in the production of antibodies, Clin. Exp. Immunol. 20: 105–111 (1975).Google Scholar
  21. 21.
    Seligman, P. A., and Allen, R. H., Characterization of the receptor for transcobalamin II isolated from human placenta, J. Biol. Chem. 253: 1766–1772 (1978).Google Scholar
  22. 22.
    Rachmilewitz, B., Manny, N., and Rachmilewitz, M., The transcobalamins in polycythemia vera, Scand. J. Haematol. 19: 453–462 (1977).CrossRefGoogle Scholar
  23. 23.
    Zittoun, J., Zittoun, R., Marquet, J., and Sultan, C., The three transcobalamins in myeboproliferative disorders and acute leukemia, Br. J. Haematol. 31: 287 (1975).CrossRefGoogle Scholar
  24. 24.
    Zittoun, J., Marquet, J., and Zittoun, R., The intracellular content of the three transcobalamins at various stages of normal and leukaemic myeloid cell development, Br. J. Haematol. 31: 299 (1975).CrossRefGoogle Scholar
  25. 25.
    Carmel, R., Vitamin B12-binding proteins in serum and plasma in various disorders: Effect of anticoagulants, Am. J. Clin. Pathol. 69: 319–325 (1978).Google Scholar
  26. 26.
    Gimsing, P., and Hippe, E., Increased concentration of transcobalamin I in a patient with metastatic carcinoma of the lung, Scand. J. Haematol. 21: 243–249 (1978).CrossRefGoogle Scholar
  27. 27.
    Nexe, E., Olesen, H., Neredam, K., and Schwarz, M., A rare case of megaloblastic anaemia caused by disturbances in the plasma cobalamin binding proteins in a patient with hepatocellular carcinoma, Scand. J. Haematol. 14: 320–327 (1975).CrossRefGoogle Scholar
  28. 28.
    Carmel, R., and Hollander, D., Extreme elevation of transcobalamin II levels in multiple myeloma and other disorders, Blood 51: 1057–1063 (1978).Google Scholar
  29. 29.
    England, J. M., Tavill, A. S., and Chanarin, I. Hepatic synthesis of transcobalamin II in the rat, Clin. Sci. Mol. Biol. 45: 479–483 (1973).Google Scholar
  30. 30.
    Schonau-Jorgensen, F., Vitamin B12 and its binding proteins in cirrhosis and infectious hepatitis, Scand. J. Haematol. 7: 322–324 (1970).CrossRefGoogle Scholar
  31. 31.
    Rachmilewitz, M., Moshkowitz, B. Rachmilewitz, B., Grossowicz, N., and Gross, J., Serum vitamin B12 binding proteins in viral hepatitis, Eur. J. Clin. Invest. 2: 239–242 (1972).CrossRefGoogle Scholar
  32. 32.
    Frater-Schroder, M., Hitzig, W. H., Grob, P. J., and Kenny, A. B., Increased unsaturated transcobalamin II in active autoimmune disease, Lancet 2, 238-239 (1958).Google Scholar
  33. 33.
    Carmel, R., and Baril, L., Circulating immunoglobulin-transcobalamin I (R-binder) complexes, J. Lab. Clin. Med. 91: 769–779 (1978).Google Scholar
  34. 34.
    Olesen, H., Horn, B. L., and Schwartz, M., Antibody to transcobalamin II in patients treated with long acting B12 preparations, Scand. J. Haematol. 5: 5–16 (1968) .Google Scholar
  35. 35.
    Carmel, R., Tatsis, B., and Baril, L., Circulating antibody to transcobalamin II causing retention of vitamin B12 in the blood, Blood 49: 987–1000 (1977).Google Scholar
  36. 36.
    Carmel, R., and Baril, L., Circulating transcobalamin I (R-binder) complexes, J. Lab. Clin. Med. 91: 769–779 (1978).Google Scholar
  37. 37.
    Hitzig, W. H., Dohmann, U., Pluss, H. J., and Vischer, D., Hereditary transcobalamin deficiency: Clinical findings in a new family, J. Pediatr. 85: 622–628 (1974).CrossRefGoogle Scholar
  38. 38.
    Hakami, N., Neiman, P. E., Canellos, G. P., and Lazerson, J., Neonatal megaloblastic anemia due to inherited transcobalamin II deficiency in two siblings, N. Engl. J. Med. 285: 1163–1170 (1971).CrossRefGoogle Scholar
  39. 39.
    Carmel, R., and Herbert, V., Deficiency of vitamin B12-binding alpha globulin in two brothers, Blood 33: 1–12 (1969).Google Scholar
  40. 40.
    Kane, S. P., Hoffbrand, A. V., Allen, R. H., and Neal, G., A familial abnormality of circulating B12 binding proteins: Occurrence in a family of high serum concentrations of transcobalamin II, Br. J. Haematol. 33: 249–259 (1976).CrossRefGoogle Scholar
  41. 41.
    Areekul, S., Doungbarn, J., and Panatampon, P., Serum vitamin B12 level and vitamin B12 binding proteins in pregnant women, J. Med. Assoc. Thai. 61: 202–209 (1978).Google Scholar

Copyright information

© Plenum Press, New York 1980

Authors and Affiliations

  • Samuel Natelson
    • 1
  • Ethan A. Natelson
    • 2
  1. 1.Department of Environmental Practice, College of Veterinary MedicineUniversity of TennesseeKnoxvilleUSA
  2. 2.University of Texas Medical School and St. Joseph HospitalHoustonUSA

Personalised recommendations