Physiology pp 189-219 | Cite as

Erythroclasia and Bilirubin Metabolism

  • John C. Nelson
  • Nader G. Ibraham
  • Richard D. Levere


The various components of the RES comprise the principal if not the only graveyard for senescent normal erythrocytes, and a number of its structural features are especially suited for this function. Nevertheless, the principal determinants of the duration of the erythrocyte life span are the intrinsic biochemical and biophysical properties of the erythrocytes. Thus, there is an interplay between erythrocytes which have undergone subtle changes in their properties during aging and a sensitive and highly selective system of erythroclasia; this interaction determines the site, timing, and mechanisms of erythrocyte destruction.


Heme Oxygenase Bile Pigment Porphyria Cutanea Tarda Sideroblastic Anemia Normal Erythrocyte 
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.


  1. Allison, A. C., 1960, Turnovers of erythrocytes and plasma proteins in mammals, Nature (London) 188:37.CrossRefGoogle Scholar
  2. Aoki, Y., 1980, Multiple enzymatic defects in mitochondria in hematological cells of patients with primary sideroblastic anemia, J. Clin. Invest. 66:43.PubMedCrossRefGoogle Scholar
  3. Aoki, Y., Urata, G., Wada, O., and Takaku, F., 1974, Measurement of δ-aminolevulinic acid synthetase activity in human erythroblasts, J. Clin. Invest. 53:1326.PubMedCrossRefGoogle Scholar
  4. Bakken, A. F, Thaler, M. M., and Schmid, R., 1972, Metabolic regulation of hepatic heme oxygenase activity, J. Biol. Chem. 51:530.Google Scholar
  5. Barrett, P. V. D., Cline, M. J., and Berlin, N. I., 1966, The association of the urobilin “early peak” and erythropoiesis in man, J. Clin. Invest. 45:1657.PubMedCrossRefGoogle Scholar
  6. Bartosz, G., Soszynski, M., and Retelewska, W., 1981, Aging of the erythrocyte. X. Immunoelectrophoretic studies on the denaturation of superoxide dismutase, Mech. Ageing Dev. 17:237.PubMedCrossRefGoogle Scholar
  7. Bass, N. M., Kirsch, R. E., Tuff, S. A., and Saunders, S. J., 1977, Radioimmunoassay of ligandin, Biochim. Biophys. Acta 494:131.PubMedCrossRefGoogle Scholar
  8. Bentley, S. A., 1977, Red cell survival studies reinterpreted, Clin. Haematol. 6:601.PubMedGoogle Scholar
  9. Berk, P. D., Bloomer, J. R., Howe, R. B., Blaschke, T. F., and Berlin, N. I., 1972, Bilirubin production as a measure of red cell lifespan, J. Lab. Clin. Med. 79:364.PubMedGoogle Scholar
  10. Berlin, N. I, and Berk, P. D., 1975, The biological life of the red cell, in: The Red Cell (D. M. Surgenor, ed.), pp. 957–1019, Academic Press, New York.Google Scholar
  11. Bernstein, R. E., 1959, Alterations in metabolic energetics and cation transport during aging of red cells, J. Clin. Invest. 38:1572.PubMedCrossRefGoogle Scholar
  12. Bessis, M., 1972, Cellules du sang normal et pathologique, Masson, Paris.Google Scholar
  13. Bessis, M., and Bricka, M., 1952, Aspect dynamique des cellules du sang: Son étude par la microcinematographie en contraste de phase, Rev. Hematol. 7:407.PubMedGoogle Scholar
  14. Bissell, D. M., Hammaker, L., and Schmid, R., 1972a, Liver sinusoidal cells: Identification of a subpopulation for erythrocyte catabolism, J. Cell Biol. 54:107.PubMedCrossRefGoogle Scholar
  15. Bissell, D. M., Hammaker, L., and Schmid, R., 1972b, Hemoglobin and erythrocyte catabolism in rat liver: The separate roles of parenchymal and sinusoidal cells, Blood 40:812.PubMedGoogle Scholar
  16. Blankaert, N., Gollan, J., and Schmid, R., 1979, Bilirubin diglucuronide synthesis by UDP-glucuronic acid dependent enzyme system in rat liver microsomes, Proc. Natl. Acad. Sci. USA 76:2037.CrossRefGoogle Scholar
  17. Blankaert, N., Gollan, J., and Schmid, R., 1980, Mechanism of bilirubin diglucuronide formation in intact rats, J. Clin. Invest. 65:1332.CrossRefGoogle Scholar
  18. Blekkenhorst, G. H., Eales, L., and Pimstone, N. R., 1979, Iron and porphyria cutanea tarda: Activation of choporphyrinogen decarboxylase by ferrous iron, S. Afr. Med. J. 56:918.PubMedGoogle Scholar
  19. Bocci, V., 1981, Determinants of erythrocyte ageing: A reappraisal, Br. J. Haematol. 48:515.PubMedCrossRefGoogle Scholar
  20. Bocci, V., Pessina, G. P., and Paules, L., 1980, Studies of factors regulating the ageing of human erythrocytes. III. Metabolism and fate of erythrocyte vesicles, Int. J. Biochem. 11:139.PubMedCrossRefGoogle Scholar
  21. Bonanou-Tzedaki, S. A., Sohi, M., and Arnstein, H. R. V., 1981, Regulation of erythroid cell differentiation by haemin, Cell Differ. 10:267.PubMedCrossRefGoogle Scholar
  22. Bonkowsky, H. C., Healey, J. F., Sinclair, P. R., Sinclair, J. F., and Pomeroy, J. S., 1981, Iron and the liver: Acute and long-term effects of iron-loading on hepatic haem metabolism, Biochem. J. 196:57.PubMedGoogle Scholar
  23. Bottomley, S. S., 1977, Porphyrin and iron metabolism in sideroblastic anemia, Semin. Hematol. 14:169.PubMedGoogle Scholar
  24. Bottomley, S. S., 1980, Sideroblastic anemia, in: Iron in Biochemistry and Medicine II (A. Jacobs and M. Worwood, eds.), pp. 363–392, Academic Press, New York.Google Scholar
  25. Branemark, P. I., and Bagge, V., 1977, Intravascular rheology of erythrocytes in man, Blood Cells 3:11.Google Scholar
  26. Brok, F., Ramot, B., Zwang, E., and Danon, D., 1966, Enzyme activities in human red blood cells of different age groups, Isr. J. Med. Sci. 2:291.PubMedGoogle Scholar
  27. Bunn, H. F., 1972, Erythrocyte destruction and hemoglobin catabolism, Semin. Hematol. 9:3.PubMedGoogle Scholar
  28. Cambell, F. R., 1972, Ultrastructural studies of transmural migration of blood cells in the bone marrow of rats, mice and guinea pigs, Am. J. Anat. 135:521.CrossRefGoogle Scholar
  29. Card, R. T., and Weintraub, L. R., 1971, Metabolic abnormalities of erythrocytes in severe iron deficiency, Blood 37:725.PubMedGoogle Scholar
  30. Carne, T., Tipping, E., and Ketterer, B., 1979, The binding and catalytic activities of forms of ligandin after modification of its thiol groups, Biochem. J. 177:433.PubMedGoogle Scholar
  31. Cartwright, G. E., and Deiss, A., 1975, Medical progress: Sideroblasts, siderocytes, and sideroblastic anemia, N. Engl. J. Med. 292:185.PubMedCrossRefGoogle Scholar
  32. Chandra, P., Chaudhery, S. A., Rosner, F., and Kagan, M., 1975, Transient histiocytosis with striking phagocytosis of platelets, leukocytes, and erythrocytes, Arch. Intern. Med. 135:989.PubMedCrossRefGoogle Scholar
  33. Chapman, R. G., and Schaumburg, L., 1967, Glycolysis and glycolytic enzyme activity of aging red cells in man, Br. J. Haematol. 13:665.PubMedCrossRefGoogle Scholar
  34. Chen, L. T., and Weiss, L., 1973, The role of the sinus wall in the passage of erythrocytes through the spleen, Blood 41:529.PubMedGoogle Scholar
  35. Chien, S., 1977, Principals and techniques for assessing erythrocyte deformability, Blood Cells 3:71.Google Scholar
  36. Chowdhury, J. R., Jansen, P. L. M., Fischberg, E. B., Daniller, A., and Arias, I. M., 1978, Hepatic conversion of bilirubin monoglucuronide to diglucuronide in uridine diphosphate-glucuronosyltransferase-deficient man and rat by bilirubin glucuroniside glucuronosyltransferase, J. Clin. Invest. 62:191.PubMedCrossRefGoogle Scholar
  37. Coburn, R. F., 1970, Enhancement by phenobarbital and diphenylhydantoin of carbon monoxide production in normal man, N. Engl. J. Med. 283:512.PubMedCrossRefGoogle Scholar
  38. Cokelet, G. R., and Meiselman, H. J., 1968, Rheological comparison of hemoglobin solutions and erythrocyte suspensions, Science 162:275.PubMedCrossRefGoogle Scholar
  39. Cooke, J. R., and Roberts, L. B., 1969, The binding of bilirubin to serum proteins, Clin. Chim. Acta 26:425.PubMedCrossRefGoogle Scholar
  40. Correia, M. A., and Schmid, R., 1975, Effect of cobalt on microsomal cytochrome P-450: Differences between liver and intestinal mucosa, Biochem. Biophys. Res. Commun. 65:1378.PubMedCrossRefGoogle Scholar
  41. Dabney, B. J., and Blaudet, A. L., 1977, Increase in globin chains and globin mRNA in erythroleukemia cells in response to hemin, Arch. Biochem. Biophys. 179:106.PubMedCrossRefGoogle Scholar
  42. DeBruyn, P. P. H., Michelson, S., and Thomas, T. B., 1971, The migration of blood cells of the bone marrow through the sinusoidal wall, J. Morphol. 133:417.CrossRefGoogle Scholar
  43. DeMatteis, F., 1978, Hepatic porphyrias caused by 2-allyl-2-isopropylacetamide, 3,5-diethoxycarbonyl-1,4-dihydrocollidine, griseofulvin and related compounds, in: Heme and Hemoproteins (F. DeMatteis and W. N. Aldridge, eds.), pp. 129–156, Springer-Verlag, Berlin.CrossRefGoogle Scholar
  44. DeMatteis, F., and Unseld, A., 1976, Increased liver haem degradation caused by foreign chemicals: A comparison of the effects of 2-allyl-2-isopropyla amide and cobaltous chloride, Biochem. Soc. Trans. 4:205.Google Scholar
  45. DeSchepper, J., and Vander Stock, J., 1971, Influence of sex on the urinary bilirubin excretion at increased free plasma haemoglobin levels in whole dogs and in isolated normothermic perfused dog kidneys, Experientia 27:1264.CrossRefGoogle Scholar
  46. Dresner, D., Ibraham, N. G., and Levere, R. D., 1981, Modulation of bone marrow heme and protein synthesis by trace elements, Environ. Res. 27:112.Google Scholar
  47. Drummond, G. S., and Kappas, A., 1981, Patent heme-degrading action of antimony and antimony containing parasiticidal agents, J. Exp. Med. 153:245.PubMedCrossRefGoogle Scholar
  48. Dukes, P. P., Shore, N. A., Hammond, P., Ortega, J. A., and Data, M. C., 1973, Enhancement of erythropoiesis by prostaglandins, J. Lab. Clin. Med. 82:704.PubMedGoogle Scholar
  49. Durocher, J. R., Payne, R. C., and Conrad, M. E., 1975, Role of sialic acid in erythrocyte survival, Blood 45:11.PubMedGoogle Scholar
  50. Eadie, G. S., and Brown, I. W., Jr., 1953, Red blood cell survival studies, Blood 8:1110.PubMedGoogle Scholar
  51. Ebert, P. S., and Ikawa, Y., 1974, Induction of δ-aminolevulinic acid synthetase during erythroid differentiation of cultured leukemia cells 38155, Proc. Soc. Exp. Biol. Med. 146:601.PubMedGoogle Scholar
  52. Ebert, P. S., Bonkowsky, H. L., and Deisseroth, A., 1979, Evidence for multiple sites of regulation of heme synthesis in murine erythroleukemia cells, J. Natl. Cancer Inst. 62:1247.PubMedGoogle Scholar
  53. Ehrenreich, B. A., and Cohn, Z. A., 1968, Fate of hemoglobin pinocytosed by macrophages in vitro, J. Cell Biol. 38:244.PubMedCrossRefGoogle Scholar
  54. Ehrenstein, G. V., and Lockner, D., 1958, Sites of the physiological breakdown of the red blood corpuscles, Nature (London) 181:911.CrossRefGoogle Scholar
  55. Elder, G., Gray, L. H., and Nicholson, D. C., 1972, Bile pigment fate in gastrointestinal tract, Semin. Hematol. 9:71.PubMedGoogle Scholar
  56. Evans, E. A., and Hochmuth, R. M., 1976a, Membrane visco-elasticity, Biophys. J. 16:1.PubMedCrossRefGoogle Scholar
  57. Evans, E. A., and Hochmuth, R. M., 1976b, Membrane visco-plastic flow, Biophys. J. 16:13.PubMedCrossRefGoogle Scholar
  58. Evans, E. A., Waugh, R., and Melnik, L., 1976, Elastic compressibility modulus of red cell membrane, Biophys. J. 16:585.PubMedCrossRefGoogle Scholar
  59. Feher, I., and Gidali, J., 1974, Prostaglandin E2 as stimulator of haemopoietic stem cell proliferation, Nature (London) 247:550.CrossRefGoogle Scholar
  60. Finch, C. A., Hegsted, M., Kinney, T. D., Thomas, E. D., Roth, C. E., Haskins, D., Finch, S., and Fluharty, R. G., 1950, Iron metabolism: The pathophysiology of iron storage, Blood 5:983.PubMedGoogle Scholar
  61. Fink, G., and Fisher, J. W., 1977, Stimulation of erythropoiesis by beta adrenergic agonists. I. Characterization of activity in polycythemic mice, J. Pharmacol. Exp. Ther. 202:192.PubMedGoogle Scholar
  62. Freedman, M. L., and Rosman, J., 1976, A rabbit reticulocyte model for the role of hemin-controlled repressor in hypochronic anemia, J. Clin. Invest. 57:594.PubMedCrossRefGoogle Scholar
  63. Frenck, T. J., and Jacobs, P., 1976, Sideroblastic anemia associated with iron overload treated with phlebotomy, S. Afr. Med. J. 50:596.Google Scholar
  64. Friend, C., Scher, W., Holland, J. G., and Sato, R., 1971, Hemoglobin synthesis in murine virusinduced leukemic cells in vitro: Stimulation of erythroid differentiation by dimethyl sulfoxide, Proc. Natl. Acad. Sci. USA 68:378.PubMedGoogle Scholar
  65. Frydman, R. B., Awruch, J., Tomaro, M. L., and Frydman, B., 1979, Concerning the specificity of heme oxygenase: The enzymatic oxidation of synthetic hemins, Biochem. Biophys. Res. Commun. 87:928.PubMedCrossRefGoogle Scholar
  66. Ganzoni, A. M., Oakes, R., and Hillman, R. S., 1971, Red cell aging in vivo, J. Clin. Invest. 50:1373.PubMedCrossRefGoogle Scholar
  67. Gemsa, D., Woo, C. H., Webb, D., Fudenberg, H. H., and Schmid, R., 1975, Erythrophagocytosis by macrophages: Suppression of heme oxygenase by cyclic AMP, Cell. Immunol. 15:21.PubMedCrossRefGoogle Scholar
  68. Gidari, A. S., and Levere, R. D., 1977, Enzymatic formation and cellular regulation of heme synthesis, Semin. Hematol. 14:145.PubMedGoogle Scholar
  69. Goldstein, G. W., Hammaker, L., and Schmid, R., 1968, The catabolism of Heinz bodies: An experimental model demonstrating conversion to non-bilirubin catabolites, Blood 31:388.PubMedGoogle Scholar
  70. Granick, J. L., and Sassa, A., 1978, Hemin control of heme biosynthesis in mouse Friend virustransformed erythroleukemia cells in culture, J. Biol. Chem. 253:5402.PubMedGoogle Scholar
  71. Gray, C. H., Kulezycka, A., Nicholson, D. C., Magnus, I. A., and Rimington, C., 1964, Isotope studies on a case of erythropoietic protoporphyria, Clin. Sci. 26:7.PubMedGoogle Scholar
  72. Graziano, J. H., and Cerami, A., 1977, Chelation therapy for the treatment of thalassemia, Semin. Hematol. 14:127.PubMedGoogle Scholar
  73. Heilmeyer, L., 1966, Disturbances in Heme Synthesis, pp. 103–178, Thomas, Springfield, Ill.Google Scholar
  74. Hines, J. D., 1976, Effect of pyridoxine plus chronic phlebotomy on the function and morphology of bone marrow and liver in pyridoxine-responsive sideroblastic anemia, Semin. Hematol. 13:133.PubMedGoogle Scholar
  75. Hochmuth, R. M., Mohandas, N., and Blackshear, P. L., Jr., 1973, Measurement of the elastic modulus for red cell membrane using a fluid mechanical technique, Biophys. J. 13:747.PubMedCrossRefGoogle Scholar
  76. Hoffman, L. M., and Ross, J., 1980, The role of heme in the maturation of erythroblasts: The effects of inhibition of pyridoxine metabolism, Blood 55:762.PubMedGoogle Scholar
  77. Hoffman, R., Ibraham, N. G., Murnane, M. J., Diamond, A., Forget, B. G., and Levere, R. D., 1980, Hemin control of heme biosynthesis and catabolism in a human leukemia cell line, Blood 56:567.PubMedGoogle Scholar
  78. Hughes-Jones, N. C., 1961, The use of 51Cr and 59Fe as red cell labels to determine the fate of normal erythrocytes in the rabbit, Clin. Sci. 20:315.PubMedGoogle Scholar
  79. Ibraham, G. W., Schwartz, S., and Watson, C. J., 1966, Early labeling of bilirubin from glycine and 8-aminolevulinic acid in bile fistula dogs, with special reference to stimulated versus suppressed erythropoiesis, Metabolism 15:1129.CrossRefGoogle Scholar
  80. Ibraham, N. G., and Levere, R. D., 1980, Nucleotide requirements for the bone marrow heme oxygenase system, Life Sci. 26:525.CrossRefGoogle Scholar
  81. Ibraham, N. G., Gruenspecht, N. R., and Freedman, M. L., 1978, Hemin feedback inhibition at reticulocyte 8-aminolevulinic acid synthetase and δ-aminolevulinic acid dehydratase, Biochem. Biophys. Res. Commun. 80:722.CrossRefGoogle Scholar
  82. Ibraham, N. G., Hoffstein, S. T., and Freedman, M. L., 1979, Induction of liver cell haem oxygenase in iron-overloaded rats, Biochem. J. 180:257.Google Scholar
  83. Ibraham, N. G., Lutton, J., and Levere, R. D., 1980, A study of heme synthetic and degradative enzymes during in vitro erythroid colony development, Clin. Res. 28:314A.Google Scholar
  84. Ibraham, N. G., Nelson, J. C., and Levere, R. D., 1981b, Control of 8-arninolevulinate synthase and haem oxygenase in chronic iron-overloaded rats, Biochem. J. 200:35.Google Scholar
  85. Ibraham, N. G., Lutton, J., and Levere, R. D., 1982a, The role of heme biosynthetic and degradative enzymes in erythroid colony development: The effect of hemin, Br. J. Haematol. 50:17.CrossRefGoogle Scholar
  86. Ibraham, N. G., Hoffman, R., Lutton, J. D., Kim Ritchey, A., and Levere, R. D., 1982b, Studies of heme metabolism in sideroblastic anemia, Blood 60:68.Google Scholar
  87. Ibraham, N. G., Hoffman, R., Lutton, J. D., Hoffman, R., Ritchey, A., and Levere, R. D., 1983, Examination of abnormalities of heme synthesis in sideroblastic erythroid cells, Clin. Res. 31(2):315.Google Scholar
  88. Israels, L. G., Skanderberg, J., Goyda, H., Zingg, W., and Zipursky, A., 1963, A study of the earlylabelled fraction of bile pigment: The effect of altering erythropoiesis on the incorporation of [2-14C]glycine into haem and bilirubin, Br. J. Haematol. 9:50.CrossRefGoogle Scholar
  89. Jacob, H. S., 1974, Pathologic states of the erythrocyte membrane, Hosp. Pract. 9:47.Google Scholar
  90. Jansen, P. L. M., Chowdhury, J. R., Fischberg, E. B., and Arias, I. M., 1977, Enzymatic conversion of bilirubin monoglucuronide to diglucuronide by rat liver plasma membranes, J. Biol Chem. 252:2710.PubMedGoogle Scholar
  91. Kappas, A., and Maines, M. D., 1976, Tin: A potent inducer of heme oxygenase in kidney, Science 192:60.PubMedCrossRefGoogle Scholar
  92. Kay, M. M. B., 1975, Mechanism of removal of senescent cells by human macrophages in situ, Proc. Natl. Acad. Sci. USA 72:3521.PubMedCrossRefGoogle Scholar
  93. Kay, M. M. B., 1978, Role of physiological autoantibody in the removal of senescent human red cells, J. Supramol. Struct. 9:555.PubMedCrossRefGoogle Scholar
  94. Keene, W. R., and Jandl, J. H., 1965, Studies of the reticuloendothelial mass and sequestering functions of rat bone marrow, Blood 26:157.PubMedGoogle Scholar
  95. Keitt, A. S., and Bennett, D. C., 1966, Pyruvate kinase deficiency and related disorders of red cell glycolysis, Am. J. Med. 41:762.PubMedCrossRefGoogle Scholar
  96. Kendrew, J. C., Dickerson, R. E., Strandberg, B. E., Hart, R. G., Davies, D. R., Phillips, D. C., and Shore, V. C., 1960, Structure of myoglobin: A three-dimensional Fourier synthesis at 2Å resolution, Nature (London) 185:422.CrossRefGoogle Scholar
  97. Ketterer, B., Tipping, E., Meuweissen, J., and Beale, D., 1975, Ligandin, Biochem. Soc. Trans. 3:626.PubMedGoogle Scholar
  98. King, R. F. G. J., and Brown, S. B., 1978, The mechanism of haem catabolism: A study of haem breakdown in spleen microsomal fraction and in a model system by 18O labelling and metal substitution, Biochem. J. 174:103.PubMedGoogle Scholar
  99. Kochen, J., Ibraham, N., Lutton, J., and Levere, R., 1981, Congenital sideroblastic anemia (CSA): A microenvironment defect, Pediatr. Res. 15:827.Google Scholar
  100. Kreimer-Birnbaum, M., Pinkerton, P. H., Bannerman, R. M., and Hutchison, H. E., 1966, Dipyrrolic urinary pigments in congenital Heinz-body anaemia due to Hb Koln and in thalassaemia, Br. Med. J. 2:396.PubMedCrossRefGoogle Scholar
  101. Krögh, A., 1930, The Anatomy and Physiology of Capillaries, Hafner, New York.Google Scholar
  102. Kushner, J. P., Steinmuller, D. P., and Lee, G. R., 1975, The role of iron in the pathogenesis of porphyria cutanea tarda. II. Inhibition of uroporphyrinogen decarboxylase, J. Clin. Invest. 56:661.PubMedCrossRefGoogle Scholar
  103. La Celle, P. L., and Arkin, B., 1970, Acquired rigidity: A possible determinant of normal RBC life span, Blood 36:837.Google Scholar
  104. Landaw, S. A., Callahan, E. W., Jr., and Schmid, R., 1970, Catabolism of heme in vivo: Comparison of the simultaneous production of bilirubin and carbon monoxide, J. Clin. Invest. 49:914.PubMedCrossRefGoogle Scholar
  105. Layrisse, M., Linaries, J., and Roche, M., 1965, Excess hemolysis in subjects with severe iron deficiency anemia associated and nonassociated with hookworm infection, Blood 25:73.PubMedGoogle Scholar
  106. Leblond, P. F., Lyonnais, J., and Delage, J. M., 1978a, Erythrocyte populations in pyruvate kinase deficiency anemia following splenectomy. I. Cell morphology, Br. J. Haematol. 39:55.PubMedCrossRefGoogle Scholar
  107. Leblond, P. F., Coulombe, L., and Lyonnais, J., 1978b, Erythrocyte population in pyruvate kinase deficiency anemia following splenectomy. IL Cell deformability, Br. J. Haematol. 39:63.PubMedCrossRefGoogle Scholar
  108. Lee, G. R., MacDiarmid, W. D., and Cartwright, G. E., 1968, Hereditary, X-linked, siderochrestic anemia: The isolation of two erythrocyte populations differing in Xga blood type and porphyrin content, Blood 32:59.PubMedGoogle Scholar
  109. Levere, R. D., and Granick, S., 1965, Control of hemoglobin synthesis in the cultured chick blastoderm by 8-aminolevulinic acid synthase: Increase in the rate of hemoglobin formation with δ-aminolevulinic acid, Proc. Natl. Acad. Sci. USA 54:134.PubMedCrossRefGoogle Scholar
  110. Levere, R. D., and Granick, S., 1967. Control of hemoglobin synthesis in the cultured chick blastoderm, J. Biol. Chem. 242:1903.PubMedGoogle Scholar
  111. Levitt, M., Schacter, B. A., Ziporsky, A., and Israels, L. G., 1968, The nonerythropoietic component of early bilirubin, J. Clin. Invest. 47:1281.PubMedCrossRefGoogle Scholar
  112. Ley, T. J., DeSimone, J., Anagnov, N. P., Keller, G. H., Humphries, R. K., Turner, P. H., Young, N. S., Heller, P., and Nienhms, A. W., 1982, 5-Azacytidine selectively increases globin synthesis in a patient with β-thalassemia, N. Engl. J. Med. 307:1469.PubMedCrossRefGoogle Scholar
  113. Litwack, G., Ketterer, B., and Arias, I. M., 1971, Ligandin: A hepatic protein which binds steroids, bilirubin, carinogens and a number of exogenous organic ions, Nature (London) 234:466.CrossRefGoogle Scholar
  114. Lodish, H. L., 1973, Biosynthesis of reticulocyte membrane proteins by membrane-free polyribosomes, Proc. Natl. Acad. Sci. USA 70:1526.PubMedCrossRefGoogle Scholar
  115. London, I. M., and West, R., 1950, The formation of bile pigment in pernicious anemia, J. Biol. Chem. 184:359.PubMedGoogle Scholar
  116. Lorand, L., Siefring, G. E., Jr., and Lowe-Krenz, L., 1979, Enzymatic basis of membrane stiffening in human erythrocytes, Semin. Hematol. 16:65.PubMedGoogle Scholar
  117. Lux, S. E., 1979, Spectrin-actin membrane skeleton of normal and abnormal red blood cells, Semin. Hematol. 16:21.PubMedGoogle Scholar
  118. McKee, L. C., Jr., Wasson, M., and Heyssel, R. M., 1968, Experimental iron deficiency in the rat: The use of 51Cr, DF32P and 59Fe to detect haemolysis of iron-deficient cells, Br. J. Haematol. 14:87.PubMedCrossRefGoogle Scholar
  119. Maines, M. D., and Kappas, A., 1974, Cobalt induction of hepatic heme oxygenase; with evidence that cytochrome P-450 is not essential for this enzyme activity, Proc. Natl. Acad. Sci. USA 71:4293.PubMedCrossRefGoogle Scholar
  120. Maines, M. D., Ibraham, N. G., and Kappas, A., 1977, Solubilization and partial purification of heme oxygenase from rat liver, J. Biol. Chem. 252:5900.PubMedGoogle Scholar
  121. Marton, P. F., 1970, Erythrophagocytosis in the human bone marrow, Scand. J. Haematol. 7:177.PubMedCrossRefGoogle Scholar
  122. Marton, P. F., 1975, Erythrophagocytosis in the human bone marrow as disclosed by iliacal bone biopsies, Scand. J. Haematol. 14:153.PubMedCrossRefGoogle Scholar
  123. Masters, B. S. S., and Schacter, B. A., 1976, The catalysis of heme degradation by purified NADPH-cytochrome C reductase in the absence of other microsomal proteins, Ann. Clin. Res. 8(17):18.PubMedGoogle Scholar
  124. Mathews, M. B., Hunt, T., and Brayley, A., 1973, Specificity of the control of protein synthesis of haemin, Nature New Biol. 243:230.PubMedCrossRefGoogle Scholar
  125. Mieschner, P., 1956, Le méchanisme de l’erythroclasie a l’etat normal, Rev. Hematol. 11:24859.Google Scholar
  126. Mohandas, N., Phillips, W. M., and Bessis, M., 1979, Red blood cell deformability and hemolytic anemias, Semin. Hematol. 16:95.PubMedGoogle Scholar
  127. Morgan, W. T., Liem, H. H., Sutor, R. P., and Müller-Eberhard, U., 1976, Transfer of heme from heme-albumin to hemopexin, Biochim. Biophys. Acta 444:435.PubMedCrossRefGoogle Scholar
  128. Nudel, U., Salmon, J. D., Terada, M., Bank, A., Rifkind, R. A., and Marks, P. A., 1977, Differential effects of chemical inducers on the expression of globin genes in murine erythroleukemia cells, Proc. Natl. Acad. Sci. USA 74:1100.PubMedCrossRefGoogle Scholar
  129. O’Carra, P. A., and Colleran, E., 1969, Haeme catabolism and coupled oxidation of haemoproteins, Fed. Eur. Biol. Soc. Lett. 5:295.CrossRefGoogle Scholar
  130. Ostrow, J. D., and Schmid, R., 1963, The protein-binding of [C14]bilirubin in human and murine serum, J. Clin. Invest. 42:1286.PubMedCrossRefGoogle Scholar
  131. Ou, L., and Smith, R. P., 1978, Hemoglobinemia in rats exposed to high altitude, Exp. Hematol. 6:473.PubMedGoogle Scholar
  132. Pasanen, A. V. O., Vuopio, P., Borgstrom, G. H., and Tenhunen, R., 1981, Heme synthesis in refractory sideroblastic anemia associated with the preleukemic syndrome, Br. J. Haematol. 27:35.Google Scholar
  133. Pettit, J. E., 1977, Spleen function, Clin. Haematol. 6:639.PubMedGoogle Scholar
  134. Pimstone, N. R., Engel, P., Tenhunen, R., Scitz, P. T., Marver, H. S., and Schmid, R., 1971a, Inducible heme oxygenase in the kidney: A model for the homeostatic control of hemoglobin catabolism, J. Clin. Invest. 50:2042.PubMedCrossRefGoogle Scholar
  135. Pimstone, N. R., Tenhunen, R., Scitz, P. T., Marver, H. S., and Schmid, R., 1971b, The enzymatic degradation of hemoglobin to bile pigments by macrophages, J. Exp. Med. 133:1264.Google Scholar
  136. Piomelli, S., Lurinsky, G., and Wasserman, L. R., 1967, The mechanism of red cell aging. I. Relationship between cell age and specific gravity evaluated by ultra-centrifugation in a discontinuous density gradient, J. Lab. Clin. Med. 69:659.PubMedGoogle Scholar
  137. Ponka, P., and Neuwirt, J., 1974, Haem synthesis and iron uptake by reticulocytes, Br. J. Haematol. 28:1.PubMedCrossRefGoogle Scholar
  138. Raffin, S. B., Choong, H. W., Roost, K. T., Price, D. C., and Schmid, R., 1974, Intestinal absorption of hemoglobin iron-heme cleavage by mucosal heme oxygenase, J. Clin. Invest. 54:1344.PubMedCrossRefGoogle Scholar
  139. Reichen, J., and Berk, P. D., 1979, Isolation of an organic anion binding protein from rat liver plasma membrane fractions by affinity chromatography, Biochem. Biophys. Res. Commun. 91:484.PubMedCrossRefGoogle Scholar
  140. Rifkind, R. A., 1966, Destruction of injured red cells in vivo, Am. J. Med. 41:711.PubMedCrossRefGoogle Scholar
  141. Robinson, S. H., 1972, Formation of bilirubin from erythroid and non-erythroid sources, Semin. Hematol. 9:43.PubMedGoogle Scholar
  142. Roost, K. T., Pimstone, N. R., Diamond, I., and Schmid, R., 1972, The formation of cerebrospinal fluid xanthochromia after subarachnoid hemorrhage: Enzymatic conversion of hemoglobin to bilirubin by the arachnoid and choroid plexus, Neurology 22:973.PubMedCrossRefGoogle Scholar
  143. Ross, J., and Sautner, D., 1976, Induction of globin mRNA accumulation by hemin in cultured erythroleukemic cells, Cell 8:513.PubMedCrossRefGoogle Scholar
  144. Rous, P., 1923, Destruction of the red blood corpuscle in health and disease, Physiol. Rev. 3:75.Google Scholar
  145. Rous, P., and Robertson, O. H., 1917, The fate of erythrocytes. I. The findings in healthy animals, J. Exp. Med. 25:651.PubMedCrossRefGoogle Scholar
  146. Rutherford, T., Thompson, G. G., and Moore, M. R., 1979, Heme biosynthesis in Friend erythroleukemia cells: Control by ferrochelatase, Proc. Natl. Acad. Sci. USA 76:833.PubMedCrossRefGoogle Scholar
  147. Sansone, G., 1962, Anemia emolitiche acquisite dell’infanzia, Pediatr. Int. 12:77.Google Scholar
  148. Sassa, S., 1976, Sequential induction of enzymes of the heme biosynthetic pathway in Friend erythroleukemia cells in culture, J. Exp. Med. 143:305.PubMedCrossRefGoogle Scholar
  149. Schacter, B. A., Yoda, B., and Israels, L. G., 1976, Human spleen heme oxygenase in normal, hemolytic and other pathological states, Ann. Clin. Res. 8(17).PubMedGoogle Scholar
  150. Schmid, R., 1978, Bilirubin metabolism: State of the art, Gastroenterology 74:1307.PubMedGoogle Scholar
  151. Schwartz, S., and Ikeda, K., 1955, Studies of porphyrin synthesis and interconversion, with special reference to certain green porphyrins in animals with experimental hepatic porphyria, in: Porphyrin Biosynthesis and Metabolism (G. E. W. Wolstenholme and E. C. P. Miller, eds.), pp. 209–228, Churchill, London.Google Scholar
  152. Scott, J. F., and Deane, H. W., 1966, Liver and gallbladder, in: Histology (R. O. Greep, ed.), 2nd ed., p. 538, McGraw-Hill, New York.Google Scholar
  153. Seeman, P., 1967, Transient holes in the erythrocyte membrane during hypotonic hemolysis and stable holes in the membrane after lysis by saponin and lysolecithin, J. Cell Biol. 32:55.PubMedCrossRefGoogle Scholar
  154. Shattil, S. J., and Cooper, R. A., 1972, Maturation of macroreticulocyte membranes in vivo, J. Lab. Clin. Med. 79:215.PubMedGoogle Scholar
  155. Sheetz, M. P., and Singer, S. J., 1977, On the mechanism of ATP-induced shape changes in human erythrocyte membranes. I. The role of the spectrin complex, J. Cell Biol. 73:638.PubMedCrossRefGoogle Scholar
  156. Sherton, C. C., and Kabat, D., 1976, Changes in RNA and protein metabolism preceding onset of hemoglobin synthesis in cultured Friend leukemia cells, Dev. Biol. 48:118.PubMedCrossRefGoogle Scholar
  157. Shotton, D., Thompson, K., Wofsy, L., and Branton, D., 1978, Appearance and distribution of surface proteins of the human erythrocyte membrane: An electron microscope and immunochemical labeling study, J. Cell Biol. 76:512.PubMedCrossRefGoogle Scholar
  158. Simpson, F., and Kling, J. M., 1967, The mechanism of denucleation in circulating erythroblasts, J. Cell Biol. 35:237.PubMedCrossRefGoogle Scholar
  159. Skutelsky, E., and Danon, D., 1970, Comparative study of nuclear expulsion from the late erythroblast and cytokinesis, Exp. Cell. Res. 60:427.PubMedCrossRefGoogle Scholar
  160. Tavassoli, M., 1977, Adaptation of marrow sinus wall to fluctuation in the rate of cell delivery: Studies in rabbits after bloodletting, Br. J. Haematol. 35:25.PubMedCrossRefGoogle Scholar
  161. Tavassoli, M., 1978, Red cell delivery and the function of the marrow-blood barrier: A review, Exp. Hematol. 6:257.PubMedGoogle Scholar
  162. Tavassoli, M., and Crosby, W. H., 1973, Fate of the nucleus of the marrow erythroblast, Science 179:912.PubMedCrossRefGoogle Scholar
  163. Teitel, P., 1977, Basic principles of the “filterability test” (FT) and analysis of erythrocyte flow behavior, Blood Cells 3:55.Google Scholar
  164. Tenhunen, R., Marver, H. S., and Schmid, R., 1969, Microsomal heme oxygenase: Characterization of the enzyme, J. Biol. Chem. 244:6388.PubMedGoogle Scholar
  165. Tenhunen, R., Marver, H. S., and Schmid, R., 1970, The enzymatic catabolism of hemoglobin: Stimulation of microsomal heme oxygenase by hemin, J. Lab. Clin. Med. 75:410.PubMedGoogle Scholar
  166. Tizianello, A., Pannacciuli, I., Salvidio, E., and Ajmar, F., 1961, A quantitative evaluation of the splenic and hepatic share in normal hemocromatosis, Acta Med. Scand. 169:303.PubMedCrossRefGoogle Scholar
  167. Tooze, J., and Davies, H. G., 1963, The occurrence and possible significance of hemoglobin in the chromosomal regions of mature erythrocyte nuclei of the newt Triturus cristatus cristatus, J. Cell Biol. 16:501.PubMedCrossRefGoogle Scholar
  168. Troxler, R. F., Dawber, N. H., and Lester, R., 1968, Synthesis of urobilinogen by broken cell preparation of intestinal bacteria, Gastroenterology 54:568.PubMedGoogle Scholar
  169. Tschudy, D. P., Hess, R. A., and Frykholm, B. C., 1981, Inhibition of δ-aminolevulinic acid dehydratase by 4,6-dioxoheptanoic acid, J. Biol. Chem. 256:9915.PubMedGoogle Scholar
  170. Ultmann, J. E., and Gordon, C. S., 1965, Life span and sites of sequestration of normal erythrocytes in normal and splenectomized mice and rats, Acta Haematol. 33:118.PubMedCrossRefGoogle Scholar
  171. Van Gastel, C., Van der Berg, D., de Gier, J., and Van Dienen, L. L. M., 1965, Some lipid characteristics of normal red blood cells of different age, Br. J. Haematol. 11:193.CrossRefGoogle Scholar
  172. Walsch, S., and Degkwitz, E., 1980, Influence of L-ascorbate deficiency on the metabolism of hepatic microsomal cytochrome P-450 in guinea pigs, Hoppe-Seyler’s Z. Physiol. Chem. 361:79.PubMedCrossRefGoogle Scholar
  173. Walter, H., and Selby, F., 1966, Counter-current distribution of red blood cells of slightly different ages, Biochim. Biophys. Acta 112:146.PubMedCrossRefGoogle Scholar
  174. Watson, C. J., 1969, Gold from dross: The first century of the urobilinoids, Ann. Intern. Med. 70:839.PubMedGoogle Scholar
  175. Wayland, H., 1973, Photosensor methods of flow measurement in the microcirculation, Microvasc. Res. 5:336.PubMedCrossRefGoogle Scholar
  176. Weed, R. I., 1970, The importance of erythrocyte deformability, Am. J. Med. 49:147.PubMedCrossRefGoogle Scholar
  177. Weed, R. L, La Celle, P. L., and Merril, E. W., 1969, Metabolic dependence of erythrocyte deformability, J. Clin. Invest. 48:795.PubMedCrossRefGoogle Scholar
  178. Weiss, L., 1962, The role of the spleen in the removal of normally aged red cells, Am. J. Anat. 111:175.CrossRefGoogle Scholar
  179. Weiss, L., 1974, A scanning electron microscopic study of the spleen, Blood 43:665.PubMedGoogle Scholar
  180. Weiss, L., and Tavassoli, M., 1970, Anatomical hazards to the passage of erythrocytes through the spleen, Semin. Hematol. 7:372.PubMedGoogle Scholar
  181. Westerman, M. P., Pierce, L. E., and Jensen, W. N., 1963, Erythrocyte lipids: A comparison of normal young and old populations, J. Clin. Lab. Med. 62:594.Google Scholar
  182. White, P., Coburn, R. F., Williams, W. J., Goldwein, M. I, Rother, M. L., and Shafer, B. C., 1967, Carbon monoxide production associated with ineffective erythropoiesis, J. Clin. Invest. 46:1986.PubMedCrossRefGoogle Scholar
  183. Williams, E. D., Szur, L., Glass, H. I, Lewis, S. M, Pettit, J. E., and Ahuja, S., 1974, Measurement of red cell destruction in the spleen, J. Lab. Clin. Med. 84:134.PubMedGoogle Scholar
  184. Wills, E. D., 1969, Lipid peroxide formation in microsomes, Biochem. J. 113:315.PubMedGoogle Scholar
  185. Winterbourn, C. C., and Batt, R. D., 1970, Lipid composition of human red cells of different ages, Biochim. Biophys. Acta 202:1.PubMedCrossRefGoogle Scholar
  186. Winterbourn, C. C., and Carrel, R. W., 1974, Studies of hemoglobin denaturation and Heinz body formation in the unstable hemoglobins, J. Clin. Invest. 54:678.PubMedCrossRefGoogle Scholar
  187. Wintrobe, M. M, Lee, G. R., Boggs, R., Bithell, T. C., Athens, J. W., and Foerster, J., 1974, Clinical Hematology, pp. 195–220, Lea & Febiger, Philadelphia.Google Scholar
  188. Woods, J. S., Kardish, R., and Fowler, B. A., 1981, Studies on the action of porphyrinogenic trace metals on the activity of hepatic uroporphyrinogen decarboxylase, Biochem. Biophys. Res. Commun. 103:264.PubMedCrossRefGoogle Scholar
  189. Yamamoto, T., Skanderberg, J., Zipursky, A., and Israels, L. G., 1965, The early appearing bilirubin: Evidence for two components, J. Clin. Invest. 44:31.PubMedCrossRefGoogle Scholar
  190. Yannoni, C. Z., and Robinson, S. H., 1978, Early labeled heme synthesis from delta-aminolevulinic acid-4-[14C] in rats: Comparison with glycine-2-[14C], Proc. Soc. Exp. Med. 158:466.Google Scholar
  191. Yoshida, T., Takohashi, S., and Kikuchi, G., 1974, Partial purification and reconstitution of the heme oxygenase sytem from pig spleen microsomes, J. Biochem. 75:1187.PubMedGoogle Scholar
  192. Zuelzer, W. W., Robinson, A. R., and Hsu, T. H. J., 1968, Erythrocyte pyruvate kinase deficiency in non-spherocytic hemolytic anemia: A system of multiple genetic markers?, Blood 32:33.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • John C. Nelson
    • 1
  • Nader G. Ibraham
    • 1
  • Richard D. Levere
    • 1
  1. 1.Department of MedicineNew York Medical CollegeValhallaUSA

Personalised recommendations