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. 1969 May;48(5):834–847. doi: 10.1172/JCI106041

Hemoglobin Hasharon (α247 his(CD5)β2): a hemoglobin found in low concentration

S Charache 1, A M Mondzac 1, U Gessner 1
PMCID: PMC322291  PMID: 5780195

Abstract

Hemoglobin Hasharon (α247 his(CD5)β2) was found to comprise only 16-19% of hemolysates of carriers. These heterozygotes appeared to have mild, compensated, hemolytic anemia. Hb Hasharon was more heat-labile than hemoglobins A, S, or C. Its specific activity was higher than that of Hb A after administration of 59Fe to two carriers. When hemoglobin synthesis by bone marrow cells was studied in vitro, about 18% of incorporated leucine appeared in the Hb Hasharon fraction. It is suggested that Hb Hasharon is unstable in vivo, and that mild hemolytic anemia and a relatively small decrease in its concentration in hemolysates result from its denaturation within red cells. Decreased synthesis, which appears to be the major cause of the small amount of abnormal hemoglobin, may protect heterozygotes from clinically significant hemolytic anemia.

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Selected References

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  1. ALTMAN K. I., IZZO M. J., SWISHER S. N., YOUNG L. E. Studies on spontaneous in vitro autohemolysis in hemolytic disorders. Blood. 1956 Nov;11(11):977–997. [PubMed] [Google Scholar]
  2. BACHMANN F., MARTIHR Hemoglobin Zurich. II. Physicochemical properties of the abnormal hemoglobin. Blood. 1962 Sep;20:272–286. [PubMed] [Google Scholar]
  3. BOI-DOKU F. S., LEHMANN H., BEALE D. HAEMOGLOBIN GACCA. Nature. 1964 Jul 25;203:363–365. doi: 10.1038/203363a0. [DOI] [PubMed] [Google Scholar]
  4. BOYER S. H., HATHAWAY P., GARRICK M. D. MODULATION OF PROTEIN SYNTHESIS IN MAN: AN IN VITRO STUDY OF HEMOGLOBIN SYNTHESIS BY HETEROZYGOTES. Cold Spring Harb Symp Quant Biol. 1964;29:333–346. doi: 10.1101/sqb.1964.029.01.036. [DOI] [PubMed] [Google Scholar]
  5. Beretta A., Prato V., Gallo E., Lehmann H. Haemoglobin Torino--alpha-43 (CD1) phenylalanine replaced by valine. Nature. 1968 Mar 16;217(5133):1016–1018. doi: 10.1038/2171016a0. [DOI] [PubMed] [Google Scholar]
  6. Bishop C., Prentice T. C. Separation of rabbit red cells by density in a bovine serum albumin gradient and correlation of red cell density with cell age after in vivo labeling with 59-Fe. J Cell Physiol. 1966 Feb;67(1):197–207. doi: 10.1002/jcp.1040670122. [DOI] [PubMed] [Google Scholar]
  7. Bunn H. F., Jandl J. H. Exchange of heme among hemoglobin molecules. Proc Natl Acad Sci U S A. 1966 Sep;56(3):974–978. doi: 10.1073/pnas.56.3.974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. CONLEY C. L., WEATHERALL D. J., RICHARDSON S. N., SHEPARD M. K., CHARACHE S. Hereditary persistence of fetal hemoglobin: a study of 79 affected persons in 15 Negro families in Baltimore. Blood. 1963 Mar;21:261–281. [PubMed] [Google Scholar]
  9. Carrell R. W., Lehmann H., Lorkin P. A., Raik E., Hunter E. Haemoglobin sydney: Beta-67 (E11) valine modified to alanine: an emerging pattern of unstable haemoglobins. Nature. 1967 Aug 5;215(5101):626–628. doi: 10.1038/215626a0. [DOI] [PubMed] [Google Scholar]
  10. Clegg J. B., Naughton M. A., Weatherball D. J. Abnormal human haemoglobins. Separation and characterization of the alpha and beta chains by chromatography, and the determination of two new variants, hb Chesapeak and hb J (Bangkok). J Mol Biol. 1966 Aug;19(1):91–108. doi: 10.1016/s0022-2836(66)80052-9. [DOI] [PubMed] [Google Scholar]
  11. Cline A. L., Bock R. M. Translational control of gene expression. Cold Spring Harb Symp Quant Biol. 1966;31:321–333. doi: 10.1101/sqb.1966.031.01.042. [DOI] [PubMed] [Google Scholar]
  12. DANON D., MARIKOVSKY V. DETERMINATION OF DENSITY DISTRIBUTION OF RED CELL POPULATION. J Lab Clin Med. 1964 Oct;64:668–674. [PubMed] [Google Scholar]
  13. Dacie J. V., Shinton N. K., Gaffney P. J., Jr, Lehmann H. Haemoglobin Hammersmith (beta-42 (CDI) Phe replaced by ser). Nature. 1967 Nov 18;216(5116):663–665. doi: 10.1038/216663a0. [DOI] [PubMed] [Google Scholar]
  14. FESSAS C., KARAKLIS A., LOUKOPOULOS D., STAMATOYANNOPOULOS G., FESSAS P. HAEMOGLOBIN NICOSIA. AN ALPHA-CHAIN VARIANT AND ITS COMBINATION WITH BETA-THALASSAEMIA. Br J Haematol. 1965 May;11:323–330. doi: 10.1111/j.1365-2141.1965.tb06592.x. [DOI] [PubMed] [Google Scholar]
  15. GABUZDA T. G., NATHAN D. G., GARDNER F. H. THE METABOLISM OF THE INDIVIDUAL C14 LABELED HEMOGLOBINS IN PATIENTS WITH H-THALASSEMIA, WITH OBSERVATIONS ON RADIOCHROMATE BINDING TO THE HEMOGLOBINS DURING RED CELL SURVIVAL. J Clin Invest. 1965 Feb;44:315–325. doi: 10.1172/JCI105145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. GRIMES A. J., MEISLER A., DACIE J. V. CONGENITAL HEINZ-BODY ANAEMIA. FURTHER EVIDENCE ON THE CAUSE OF HEINZ-BODY PRODUCTION IN RED CELLS. Br J Haematol. 1964 Jul;10:281–290. doi: 10.1111/j.1365-2141.1964.tb00704.x. [DOI] [PubMed] [Google Scholar]
  17. HEYWOOD J. D., KARON M., WEISSMAN S. STUDIES OF IN VITRO SYNTHESIS OF HETEROGENIC HEMOGLOBINS. J Clin Invest. 1964 Dec;43:2368–2376. doi: 10.1172/JCI105111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. HUISMAN T. H., MEYERING C. A. Studies on the heterogeneity of hemoglobin. I. The heterogeneity of different human hemoglobin types in carboxymethylcellulose and in amberlite IRC-50 chromatography qualitative aspects. Clin Chim Acta. 1960 Jan;5:103–123. doi: 10.1016/0009-8981(60)90098-x. [DOI] [PubMed] [Google Scholar]
  19. Halbrecht I., Isaacs W. A., Lehmann H., Ben-Porat F. Hemoglobin hasharon (alpha-47 aspartic acid--histidine). Isr J Med Sci. 1967 Nov-Dec;3(6):827–831. [PubMed] [Google Scholar]
  20. Huisman T. H., Dozy A. M. Studies on the heterogeneity of hemoglobin. IX. The use of Tris(hydroxymethyl)aminomethanehcl buffers in the anion-exchange chromatography of hemoglobins. J Chromatogr. 1965 Jul;19(1):160–169. doi: 10.1016/s0021-9673(01)99434-8. [DOI] [PubMed] [Google Scholar]
  21. Itano H. A. Genetic regulation of peptide synthesis in hemoglobins. J Cell Physiol. 1966 Jun;67(3 Suppl):65–76. doi: 10.1002/jcp.1040670408. [DOI] [PubMed] [Google Scholar]
  22. Jacob H. S., Brain M. C., Dacie J. V., Carrell R. W., Lehmann H. Abnormal haem binding and globin SH group blockade in unstable haemoglobins. Nature. 1968 Jun 29;218(5148):1214–1217. doi: 10.1038/2181214a0. [DOI] [PubMed] [Google Scholar]
  23. Jones R. V., Grimes A. J., Carrell R. W., Lehmann H. Köln haemoglobinopathy. Further data and a comparison with other hereditary Heinz body anaemias. Br J Haematol. 1967 May;13(3):394–408. doi: 10.1111/j.1365-2141.1967.tb08754.x. [DOI] [PubMed] [Google Scholar]
  24. Kazazian H. H., Jr, Itano H. A. Studies on the quantitative control of polypeptide synthesis in human reticulocytes. J Biol Chem. 1968 Apr 25;243(8):2048–2055. [PubMed] [Google Scholar]
  25. Kreimer-Birnbaum M., Pinkerton P. H., Bannerman R. M., Hutchison H. E. Metabolism of hemoglobin Köln, an unstable hemoglobin. Nature. 1968 Aug 3;219(5153):494–495. doi: 10.1038/219494a0. [DOI] [PubMed] [Google Scholar]
  26. LEVERE R. D., LICHTMAN H. C., LEVINE J. EFFECT OF IRON-DEFICIENCY ANAEMIA ON THE METABOLISM OF THE HETEROGENIC HAEMOGLOBINS IN SICKLE CELL TRAIT. Nature. 1964 May 2;202:499–501. doi: 10.1038/202499a0. [DOI] [PubMed] [Google Scholar]
  27. LEVERE R. D., LICHTMAN H. C. METABOLISM OF HETEROGENIC HEMOGLOBINS. FE59 INCORPORATION IN SICKLE CELL TRAIT. Blood. 1963 Sep;22:334–341. [PubMed] [Google Scholar]
  28. LIDDELL J., BROWN D., BEALE D., LEHMANN H., HUNTSMAN R. G. A NEW HAEMOGLOBIN-JA OXFORD FOUND DURING A SURVEY OF AN ENGLISH POPULATION. Nature. 1964 Oct 17;204:269–270. doi: 10.1038/204269a0. [DOI] [PubMed] [Google Scholar]
  29. Marshall R. E., Caskey C. T., Nirenberg M. Fine structure of RNA codewords recognized by bacterial, amphibian, and mammalian transfer RNA. Science. 1967 Feb 17;155(3764):820–826. doi: 10.1126/science.155.3764.820. [DOI] [PubMed] [Google Scholar]
  30. Nathan D. G., Gunn R. B. Thalassemia: the consequences of unbalanced hemoglobin synthesis. Am J Med. 1966 Nov;41(5):815–830. doi: 10.1016/0002-9343(66)90039-8. [DOI] [PubMed] [Google Scholar]
  31. Ostertag W., Smith E. W. Hb Sinai, a new alpha chain mutant alpha his 47. Humangenetik. 1968;6(4):377–379. doi: 10.1007/BF00286809. [DOI] [PubMed] [Google Scholar]
  32. PHILIPPS G. R. HAEMOGLOBIN SYNTHESIS AND POLYSOMES IN INTACT RETICULOCYTES. Nature. 1965 Feb 6;205:567–570. doi: 10.1038/205567a0. [DOI] [PubMed] [Google Scholar]
  33. Perutz M. F., Lehmann H. Molecular pathology of human haemoglobin. Nature. 1968 Aug 31;219(5157):902–909. doi: 10.1038/219902a0. [DOI] [PubMed] [Google Scholar]
  34. Perutz M. F., Muirhead H., Cox J. M., Goaman L. C. Three-dimensional Fourier synthesis of horse oxyhaemoglobin at 2.8 A resolution: the atomic model. Nature. 1968 Jul 13;219(5150):131–139. doi: 10.1038/219131a0. [DOI] [PubMed] [Google Scholar]
  35. Piomelli S., Lurinsky G., Wasserman L. R. The mechanism of red cell aging. I. Relationship between cell age and specific gravity evaluated by ultracentrifugation in a discontinuous density gradient. J Lab Clin Med. 1967 Apr;69(4):659–674. [PubMed] [Google Scholar]
  36. Pootrakul S., Wasi P., Na-Nakorn S. Haemoglobin J-Bangkok: a clinical, haematological and genetical study. Br J Haematol. 1967 May;13(3):303–309. doi: 10.1111/j.1365-2141.1967.tb08744.x. [DOI] [PubMed] [Google Scholar]
  37. RANNEY H. M., KONO P. Studies of the incoporation of Fe59 into normal and abnormal hemoglobins. J Clin Invest. 1959 Mar;38(3):508–515. doi: 10.1172/JCI103828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. RIEDER R. F., WEATHERALL D. J. STUDIES ON HEMOGLOBIN BIOSYNTHESIS: ASYNCHRONOUS SYNTHESIS OF HEMOGLOBIN A AND HEMOGLOBIN A2 BY ERYTHROCYTE PRECURSORS. J Clin Invest. 1965 Jan;44:42–50. doi: 10.1172/JCI105125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. RIEDER R. F., ZINKHAM W. H., HOLTZMAN N. A. HEMOGLOBIN ZUERICH; CLINICAL, CHEMICAL AND KINETIC STUDIES. Am J Med. 1965 Jul;39:4–20. doi: 10.1016/0002-9343(65)90241-x. [DOI] [PubMed] [Google Scholar]
  40. RIGAS D. A., KOLER R. D. Decreased erythrocyte survival in hemoglobin H disease as a result of the abnormal properties of hemoglobin H: the benefit of splenectomy. Blood. 1961 Jul;18:1–17. [PubMed] [Google Scholar]
  41. RIGAS D. A., KOLER R. D. Ultracentrifugal fractionation of human erythrocytes on the basis of cell age. J Lab Clin Med. 1961 Aug;58:242–246. [PubMed] [Google Scholar]
  42. Rieder R. F., Bradley T. B., Jr Hemoglobin Gun Hill: an unstable protein associated with chronic hemolysis. Blood. 1968 Sep;32(3):355–369. [PubMed] [Google Scholar]
  43. SHEPARD M. K., WEATHERALL D. J., CONLEY C. L. Semi-quantitative estimation of the distribution of fetal hemoglobin in red cell populations. Bull Johns Hopkins Hosp. 1962 Jun;110:293–310. [PubMed] [Google Scholar]
  44. SHIBATA S., IUCHI I., MIYAJI T., UEDA S., TAKEDA I. HEMOLYTIC DISEASE ASSOCIATED WITH THE PRODUCTION OF ABNORMAL HEMOGLOBIN AND INTRAERYTHROCYTIC HEINZ BODIES. Nihon Ketsueki Gakkai Zasshi. 1963 Apr;26:164–173. [PubMed] [Google Scholar]
  45. SINGER K., CHERNOFF A. I., SINGER L. Studies on abnormal hemoglobins. I. Their demonstration in sickle cell anemia and other hematologic disorders by means of alkali denaturation. Blood. 1951 May;6(5):413–428. [PubMed] [Google Scholar]
  46. SINGER K., FISHER B. Studies on abnormal hemoglobins. VII. The composition of the non-S hemoglobin fraction in sickle-cell anemia bloods; a comparative quantitative study by the methods of electrophoresis and alkali denaturation. J Lab Clin Med. 1953 Aug;42(2):193–204. [PubMed] [Google Scholar]
  47. Sansone G., Carrell R. W., Lehmann H. Haemoglobin Genova: beta-28 (B10) leucine replaced by proline. Nature. 1967 May 27;214(5091):877–879. doi: 10.1038/214877a0. [DOI] [PubMed] [Google Scholar]
  48. Schneider R. G., Ueda S., Alperin J. B., Brimhall B., Jones R. T. Hemoglobin sealy (alpha 2-47His-beta 2): a new variant in a Jewish family. Am J Hum Genet. 1968 Mar;20(2):151–156. [PMC free article] [PubMed] [Google Scholar]
  49. Shaeffer J. R., Trostle P. K., Evans R. F. Rabbit hemoglobin biosynthesis: use of human hemoglobin chains to study molecule completion. Science. 1967 Oct 27;158(3800):488–490. doi: 10.1126/science.158.3800.488. [DOI] [PubMed] [Google Scholar]
  50. Slater L. M., Muir W. A., Weed R. I. Influence of splenectomy on insoluble hemoglobin inclusion bodies in beta thalassemic erythrocytes. Blood. 1968 Jun;31(6):766–777. [PubMed] [Google Scholar]
  51. THOMPSON R. B., MITCHENER J. W., HUISMAN T. H. Studies on the fetal hemoglobin in the persistent high Hb-F anomaly. Blood. 1961 Sep;18:267–284. [PubMed] [Google Scholar]
  52. THORUP O. A., ITANO H. A., WHEBY M., LEAVELL B. S. Hemoglobin J. Science. 1956 May 18;123(3203):889–890. doi: 10.1126/science.123.3203.889. [DOI] [PubMed] [Google Scholar]
  53. VENTRUTO V., BAGLIONI C., DEROSA L., BIANCHI P., COLOMBO B., QUATTRIN N. HAEMOGLOBIN CASERTA: AN ABNORMAL HAEMOGLOBIN OBSERVED IN A SOUTHERN ITALIAN FAMILY. Scand J Haematol. 1965;2:118–125. doi: 10.1111/j.1600-0609.1965.tb01287.x. [DOI] [PubMed] [Google Scholar]
  54. WEATHERALL D. J., BOYER S. H., 4th Evidence for the genetic identity of alpha chain determinants in hemoglobins A, A2 and F. Bull Johns Hopkins Hosp. 1962 Jan;110:8–22. [PubMed] [Google Scholar]
  55. WEATHERALL D. J. HEMOGLOBIN J (BALTIMORE) COEXISTING IN A FAMILY WITH HEMOGLOBIN S. Bull Johns Hopkins Hosp. 1964 Jan;114:1–12. [PubMed] [Google Scholar]
  56. Wennberg E., Weiss L. Splenic erythroclasia: an electron microscopic study of hemoglobin H disease. Blood. 1968 Jun;31(6):778–790. [PubMed] [Google Scholar]
  57. Winslow R. M., Ingram V. M. Peptide chain synthesis of human hemoglobins A and A2. J Biol Chem. 1966 Mar 10;241(5):1144–1149. [PubMed] [Google Scholar]
  58. YAKULIS V. J., HELLER P. AN ELUTION TEST FOR THE VISUALIZATION OF HEMOGLOBIN S IN BLOOD SMEARS. Blood. 1964 Aug;24:198–201. [PubMed] [Google Scholar]

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