Hemopexin: Iron Recycling

  • Samuel Natelson
  • Ethan A. Natelson


There is a significant amount of methemoglobin circulating in human plasma at all times. In this compound, the iron in the iron-porphyrin complex is in the trivalent state and does not participate in oxygen exchange. The prosthetic group is called ferriprotoporphyrin IX. The free base is called hematin, and the chloride salt hemin (see Volume 2, p. 469). Some use the expressions ferriheme for ferriprotoporphyrin IX and ferrihemoglobin to signify methemoglobin.


Electron Spin Resonance Muscular Dystrophy Pernicious Anemia Dengue Hemorrhagic Fever Rose Bengal 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Selected Reading

  1. Zinkham, W. T., Vangrov, J. S., Dixon, S. M., and Hutchinson, J. L., Observations on the rate and mechanism of hemolysis in individuals with Hb-Zurich (Hb-Zurich, HisE7, 63, beta, leads to arg.) concentration of haptoglobin and hemopexin in the serum, Johns Hopkins Med. J. 144: 37–40 (1979).Google Scholar
  2. Muller-Eberhard, U., and Lieur, H. H., Hemopexin, the heure binding serum glycoprotein, in Structure and Function of Plasma Proteins, A. C. Allison, Ed., Plenum Press, New York (1974).Google Scholar
  3. Morgan, William T., The binding and transport of heure by hemopexin, Ann. Clin. Res. 8 (suppl.): 223–232 (1976).Google Scholar
  4. Muller-Eberhard, U., Hemopexin, N. Engl. J. Med. 283: 1090–1094 (1970).CrossRefGoogle Scholar
  5. Conway, T. P., and Muller-Eberhard, U., Interaction of hemopexin with water-soluble porphyrine, Arch. Biochem. Biophys. 172: 558–564 (1976).CrossRefGoogle Scholar


  1. 1.
    Grabar, P., DeVaux St. Cyr., C., and Cleve, H., Presence of ß1,ß-globulin in the perchloric acid extracts of normal human sera, Bull. Soc. Chim. Biol. 42: 853–836 (1960).Google Scholar
  2. 2.
    Heide, K., Haupt, H., Storiko, K., and Schultze, H. E., On the heure binding capacity of hemopexin, Clin. Chim. Acta 10: 460–469 (1964).CrossRefGoogle Scholar
  3. 3.
    Hanstein, A., and Muller-Eberhard, U., Concentration of serum hemopexin in healthy children and adults and in those with a variety of hematological disorders, J. Lab. Clin. Med. 71: 232–239 (1968).Google Scholar
  4. 4.
    Neale, F. C., Aber, G. M., and Northam, B. E., The demonstration of intra-vascular haemolysis by means of serum paper electrophoresis and a modification of Schumm’s reaction, J. Clin. Path. 11: 206–219 (1958).CrossRefGoogle Scholar
  5. 5.
    Seery, V. L., Hathaway, G., and Muller-Eberhard, U., Hemopexin of human and rabbit: Molecular weight and extinction coefficient, Arch. Biochem. Biophys. 150: 269–272 (1972).CrossRefGoogle Scholar
  6. 6.
    Morgan, W. T., Capra, J. D., Kehoe, J. M., and Muller-Eberhard, U., Human and rabbit hemopexins: Tryptic peptides and N-terminal sequences, FEBS Lett. 48: 109–113 (1974).CrossRefGoogle Scholar
  7. 7.
    Muller-Eberhard, U., Hemopexin, N. Engl. J. Med. 283: 1090–1094 (1970).CrossRefGoogle Scholar
  8. 8.
    Hrkal, Z., and Muller-Eberhard, U., Partial characterization of the hemebinding serum glycoproteins rabbit and human hemopexin, Biochemistry 10: 1746–1750 (1971).CrossRefGoogle Scholar
  9. 9.
    Rosen, H., and Sears, D. A., Spectral properties of hemopexin-heme: the Schumm test, J. Lab. Clin. Med. 74: 941–945 (1969).Google Scholar
  10. 10.
    Morgan, W. T., The binding and transport of heme by hemopexin, Ann. Clin. Res. 8 (suppl. 17): 223–232 (1976).Google Scholar
  11. 11.
    Aber, G. M., and Rowe, D. S., The binding of haematin by serum proteins, Br. J. Haemat. 6: 160–165 (1960).CrossRefGoogle Scholar
  12. 12.
    Allison, A. C., and Rees, W., The binding of haemoglobin by plasma proteins (haptoglobins), Br. Med. J. 2: 1137–1143 (1957).CrossRefGoogle Scholar
  13. 13.
    Bearden, A. J., Morgan, W. T., and Muller-Eberhard, U., Herne complexes of rabbit hemopexin, human hemopexin and human serum albumin: Electron spin resonance and Mossbauer spectroscopic studies, Biophys. Res. Commun. 61: 265–272 (1974).CrossRefGoogle Scholar
  14. 13a.
    Morgan, W. T., and Vickery, L. E., Magnetic and natural circular dichroism of metalloporphyrin complexes of human and rabbit hemopexin, J. Biol. Chem. 253: 2940–2943 (1978).Google Scholar
  15. 14.
    Hrkal, Z., Vodrâzka, Z., and Kalousek, I., Transfer of heme from ferrihemoglobin and ferrihemoglobin isolated chains to hemopexin, Eur. J. Biochem. 43: 73–78 (1974).CrossRefGoogle Scholar
  16. 15.
    Morgan, W. T., Muller-Eberhard, U., and Lamola, A. A., Interaction of rabbit hemopexin with bilirubin, Biochim. Biophys. Acta 532: 57–64 (1978).Google Scholar
  17. 16.
    Kelly, T. R., Klein, R. L., Porquez, J. M., and Homer, G. M., Methemalbumin in acute pancreatitis: An experimental and clinical appraisal, Ann. Surg. 175: 15–18 (1972).CrossRefGoogle Scholar
  18. 17.
    Kodiixek, M., Hrkal, Z., and Vodrâika, Z., On the molecular conformation of human haemopexin. II. Analysis of circular dichroic spectra, Biochim. Biophys. Acta 495: 268–278 (1977).Google Scholar
  19. 18.
    Kodíitek, M., Hrkal, Z., Suttnar, J., and Vodriiika, Z., On the molecular conformation of human haemopexin. I. Reactivity of the tyrosine and tryptophan side chains, Biochim. Biophys. Acta 495: 260–267 (1977).Google Scholar
  20. 19.
    Planche, Y., Dautrexvaux, M., and Biserte, G., Change of human hemopexin isoelectric point upon heure binding, FEBS Lett. 78: 291–294 (1977).CrossRefGoogle Scholar
  21. 20.
    Seery, V. L., and Muller-Eberhard, U., Binding of porphyrins to rabbit hemopexin and albumin, J. Biol. Chem. 248: 3796–3800 (1973).Google Scholar
  22. 21.
    Havez, R., Moschetto, Y., Hayem-Levy, A., and Biserte, G., Alkylation of histidine radicals at the combining site of seromucoid ß1 with hematin, Comfit. Rend. Acad. Sci. (Paris) 265: 585–589 (1967).Google Scholar
  23. 22.
    Aisen, P., Leibman, A., Harris, D. C., and Moss, T., Human hemopexin: Preparation and magnetic properties, J. Biol. Chem. 249: 6824–6827 (1974).Google Scholar
  24. 23.
    Seery, V. L., Morgan, W. T., and Muller-Eberhard, U., Interaction of rabbit hemopexin with rose bengal and photooxidation of the rose bengal-hemopexin complex, J. Biol. Chem. 250: 6439–6444 (1975).Google Scholar
  25. 24.
    Muller-Eberhard, U., and Morgan, W. T., Porphyrin-binding proteins in serum, N.Y. Acad. Sci. 244: 624–650 (1975).CrossRefGoogle Scholar
  26. 25.
    Sears, D. A., Disposal of plasma heure in normal man and patients with intravascular hemolysis, J. Clin. Invest. 49: 5–14 (1970).CrossRefGoogle Scholar
  27. 26.
    Liem, H. H., Hepatic uptake of heure and hemopexin but not albumin, Biochim. Biophys. Acta 343: 546–550 (1974).CrossRefGoogle Scholar
  28. 27.
    Lane, R. S., Rangeley, D. M., Liem, H. H., Wormsley, S., and Muller-Eberhard, U., Plasma clearance of ‘251-labeled haemopexin in normal and haemloaded rabbits, Br. J. Haematol. 25: 533–540 (1973).CrossRefGoogle Scholar
  29. 28.
    Liem, H. H., Spector, J. I., Conway, T. P., Morgan, W. T., and Muller-Eberhard, U., Effect of hemoglobin and hematin on plasma clearance of hemopexin, photo-inactivated hemopexin and albumin, Proc. Soc. Exp. Biol. Med. 148: 519–522 (1975).Google Scholar
  30. 29.
    Morgan, W. T., Liem, H. H., Sutor, R. P., and Muller-Eberhard, U., Transfer of heure from heme-albumin to hemopexin, Biochim. Biophys. Acta 444: 435–445 (1976).CrossRefGoogle Scholar
  31. 30.
    Biserte, G., Havez, R., and Laturze, J., Electrophoretic characterization and immunology of ß1 seromucoid in human blood serum, Compt. Rend. Soc. Biol. 11: 2061–2066 (1960).Google Scholar
  32. 31.
    Maines, M. D., Anders, M. W., and Muller-Eberhard, U., Studies on heure transfer from microsomal hemoproteins to heme-binding plasma proteins, Molecular Pharmacology 10: 204–213 (1974).Google Scholar
  33. 32.
    Gielen, J. E., Goujon, F. M., and Nebert, D. W., Genetic regulation of aryl hydrocarbon: Hydroxylase induction. II-Simple Mendelian expression in mouse tissues in vivo, J. Biol. Chem. 247: 1125–1137 (1972).Google Scholar
  34. 33.
    Conway, T. P., and Muller-Eberhard, U., Interaction of hemopexin with water-soluble porphyrins, Arch. Biochem. Biophys. 172: 558–564 (1976).CrossRefGoogle Scholar
  35. 34.
    Atzeni, E., Binaghi, F., and Pitzus, F., Haemopexin behaviour in an acute hyperhaemolytic crisis secondary to favism (erythrocyte glucose-6-phosphate dehydrogenase deficiency), Ric. Clin. Lab. 7: 39–43 (1977).Google Scholar
  36. 35.
    Bunn, H. F., Erythrocyte destruction and hemoglobin catabolism, Semin. Hematol. 9: 3–17 (1972).Google Scholar
  37. 36.
    Muller-Eberhard, U., and Liem, H. H., Hemopexin, the heme-binding serum ß-glycoprotein, in Structure and Function of Plasma Proteins, Vol. 1, A. C. Allison, Ed., Plenum Press, N.Y. (1974), pp. 35–53.CrossRefGoogle Scholar
  38. 37.
    Meiers, H. G., and Ippen, H., Ahemopexinemia in cutanea tarda porphyria, Klin. Wechenschr. 46: 560–561 (1968).CrossRefGoogle Scholar
  39. 38.
    Hershko, C., Annotation: The fate of circulating haemoglobin, Br. J. Haemat. 29: 199–204 (1975).CrossRefGoogle Scholar
  40. 39.
    Warnick, G. R., and Burnham, B. F., Regulation of porphyrin biosynthesis: Purification and characterization of aminolevulinic acid synthase, J. Biol. Chem. 246: 6880–6885 (1971).Google Scholar
  41. 40.
    Nyman, M., On plasma proteins with heme or hemoglobin binding capacity, Scand. J. Clin. Lab. Invest. 12: 121–130 (1960).CrossRefGoogle Scholar
  42. 41.
    Schultze, H. E., Heide, K., and Haupt, H., Characterization of highly purified hemopexin, Naturwissenschaften 48: 696–697 (1961).CrossRefGoogle Scholar
  43. 42.
    Gitlin, D., and Biasucci, A., Development of yG, yA, yM, ßIC and ßIA esterase inhibitor, ceruloplasmin, transferrin, hemopexin, haptoglobin, fibrinogen, plasminogen, a-I-antitrypsin, orosomucoid, lipoprotein, 2-macroglobulin and prealbumin in the human conceptus, J. Clin. Invest. 48: 1433–1446 (1969).CrossRefGoogle Scholar
  44. 43.
    Weippl, G., Pantlitschko, M., and Hammelmann, C., Hemopexin in cord blood, Clin. Chim. Acta 29: 338 (1970).CrossRefGoogle Scholar
  45. 44.
    Muller-Eberhard, U., and Bashore, R., Assessment of Rh disease by ratios of bilirubin to albumin and hemopexin to albumin in amniotic fluid, N. Engl. J. Med. 282: 1163–1167 (1970).CrossRefGoogle Scholar
  46. 45.
    Swahn, B., Bronnestam, R., and Dencker, S. J., On the origin of the lipoproteins in the cerebrospinal fluid, Neurology 11: 437–440 (1961).CrossRefGoogle Scholar
  47. 46.
    Muller-Eberhard, U., and Cox, K. H., Development of non-specific antibodies to rat hemopexin and albumin Evidence for immunological cross-reactivity with mouse proteins, Comp. Biochem. Physiol. 51: 47–50 (1975).Google Scholar
  48. 47.
    Thorbecke, G. J., Liem, H. H., Knight, S., Cox, K., and Muller-Eberhard, U., Sites of formation of the serum proteins transferrin and hemopexin, J. Clin. Invest. 52: 725–731 (1973).CrossRefGoogle Scholar
  49. 48.
    Muller-Eberhard, U., and English, E. C., Purification and partial characterization of human hemopexin, J. Lab. Clin. Med. 70: 619–626 (1967).Google Scholar
  50. 49.
    Shibert, E., Liem, H. H., and Muller-Eberhard, U., Studies on the induction of serum hemopexin by pentobarbitol and polycyclic hydrocarbons, Biochem. Pharmacol. 21: 1753–1761 (1972).CrossRefGoogle Scholar
  51. 50.
    Myrhed, M., Wetterberg, L., and Muller-Eberhard, U., Genetic control of serum hemopexin, Ann. Clin. Res. 8 (suppl. 17): 259–261 (1976).Google Scholar
  52. 51.
    Sears, D. A., Plasma heme-binding in patients with hemolytic disorders, J. Lab. Clin. Med. 71: 484–494 (1968).Google Scholar
  53. 52.
    Seager, J., Haemopexin, caeruloplasmin and C3: Effect of diphenylhydantoin, Clin. Chim. Acta 79: 603–606 (1977).CrossRefGoogle Scholar
  54. 53.
    Braun, H. J., and Aly, F. W., Clinical significance of the quantitative serum hemopexin determination in comparison to haptoglobin, Klin. Wochenschr. 49: 451–457 (1971).CrossRefGoogle Scholar
  55. 54.
    Braun, H. J., The significance of immunological hemopexin estimation for the diagnosis of hemolytic pancreatitis, Verhand. Deutsch. Ges. Inn. Med. 78: 1426–1429 (1972).Google Scholar
  56. 55.
    Bokisch, V. A., Top, F. H., Jr., Russell, P. K., Dixon, F. J., and Muller-Eberhard, H. J., The potential pathogenic role of complement in dengue hemorrhagic shock syndrome, N. Engl. J. Med. 289: 996–1000 (1973).CrossRefGoogle Scholar
  57. 56.
    Murray-Lyon, I. M., Studies on plasma proteins in liver disease using quantitative immunoelectrophoresis, Ph.D. dissertation. University Edinburgh, Scotland (1973).Google Scholar
  58. 57.
    Muller-Eberhard, U., Liem, H. H., Mathews-Roth, M. M., and Epstein, J. H., Plasma levels of hemopexin and albumin in disorders of porphyrin metabolism, Proc. Soc. Exp. Biol. Med. 146: 694–697 (1974).Google Scholar
  59. 58.
    Cleve, H., Alexander, K., Mitzkat, H. J., Nissen, P., and Salzmann, I., Serum proteins in diabetes mellitus: Quantitative immunological estimation of acid al-glycoprotein, Gc, a2 macroglobin and hemopexin in diabetics without angiopathy, Diabetologia 4: 48–55 (1968).CrossRefGoogle Scholar
  60. 59.
    Aakanas, W., and Mazurczak, J., The serum immunoelectrophoretic test in patients with Duchenne’s progressive muscular dystrophy: Preliminary report, Life Sci. 5: 247–251 (1966).CrossRefGoogle Scholar
  61. 60.
    Manuel, Y., DeFontaine, M. C., Bourgoin, J. J., Dargent, M., and Sonneck, J. M., Serum hemopexin levels in patients with malignant melanoma, Clin. Chim. Acta 3: 485–486 (1971).CrossRefGoogle Scholar
  62. 61.
    Snyder, S., and Ashwell, G., Quantitation of specific serum glycoproteins in malignancy, Clin. Chim. Acta 34: 449–455 (1971).CrossRefGoogle Scholar
  63. 62.
    Danieli, G. A., and Angelini, C., Duchenne carrier detection, Lancet 2: 90 (1976).CrossRefGoogle Scholar
  64. 63.
    Rowland, L. P., Layzer, R. B., and Kagen, L. J., Lack of some muscle proteins in serum of patients with Duchenne dystrophy, Arch. Neurol. 18: 272–276 (1968).CrossRefGoogle Scholar
  65. 64.
    Miller, S. E., Roses, A. P., and Appel, S. H., Scanning electron microscopy studies in muscular dystrophy, Arch. Neurol. 33: 172–174 (1976).CrossRefGoogle Scholar
  66. 65.
    Muller-Eberhard, U., Liem, H. H., Hanstein, A., and Saarinen, P. A., Studies on the disposal of intravascular heme in the rabbit, J. Lab. Clin. Med. 73: 210–218 (1969).Google Scholar
  67. 66.
    Ross, J. D., Muller-Eberhard, U., and Carroll, L. A., Pharmacologic induction of serum hemopexin by 3-methylcholanthrene and allylisopropylacetamide, J. Lab. Clin. Med. 75: 694–702 (1970);Google Scholar
  68. Ross, J. D., Muller-Eberhard, U., and Carroll, L. A., Biochem. Biophys. Res. Commun. 41: 186–193 (1970).CrossRefGoogle Scholar
  69. 67.
    Cripps, D. J., Liem, H. H., and Muller-Eberhard, U., Griseofulvin causing hyperhemopexinemia and hepatic proliferation in mice: An in vivo and in vitro study, J. Invest. Dermatol. 68: 82–87 (1977).CrossRefGoogle Scholar
  70. 68.
    Piomielli, S., Davidow, B., Guinee, V. F., Young, P., and Gay, G., The FEP (free erythrocyte porphyrins) test. A screening micromethod for lead poisoning, Pediatrics 51: 254–259 (1972).Google Scholar
  71. 69.
    Hrkal, Z., Vodrazka, Z., and Rejnkova, J., Purification of human serum hemopexin by chromatography on DEAE-cellulose, J. Chromatogr. 72: 198–201 (1972).CrossRefGoogle Scholar
  72. 70.
    Vretblad, P., and Hjorth, R., The use of wheat-germ lectinsepharose for the purification of human haemopexin, Biochem. J. 167: 759–764 (1977).Google Scholar
  73. 71.
    Hayem-Levy, A., and Havez, R., Isolation and study of human hemopexin, Clin. Chim. Acta 47: 113–122 (1973).CrossRefGoogle Scholar
  74. 72.
    Suttnar, J., Hrkal, Z., and Vodrazka, Z., Affinity chromatography of serum haemopexin, J. Chromatogr. 131: 453–457 (1977).CrossRefGoogle Scholar
  75. 73.
    Mancini, G., Carbonara, A. O., and Heremans, J. F., Immunochemical quantitation of antigens by single radial immunodiffusion, Int. J. Immunochemistry 2: 235–254 (1965).CrossRefGoogle Scholar
  76. 74.
    Laurell, C. B., Electroimmunoassay, Scand. J. Clin. Lab. Invest. 29 (suppl. 124): 21–23 (1972).CrossRefGoogle Scholar
  77. 75.
    Ganrot, P. 0., Crossed immunoelectrophoresis, Scand. J. Clin. Lab. Invest. 29 (suppl. 124): 39–44 (1972).CrossRefGoogle Scholar
  78. 76.
    Rosen, H., and Sears, D. A., Spectral properties of hemopexin heure: The Schumm test, J. Lab. Clin. Med. 74: 941–945 (1969).Google Scholar
  79. 77.
    Ursing, B., Clinical and immunoelectrophoretic studies on cerebrospinal fluid in virus meningoencephalitis and bacterial meningitis, Acta Med. Scand. 177 (suppl. 429): 1–99 (1965).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