• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of jcinvestThe Journal of Clinical InvestigationCurrent IssueArchiveSubscriptionAbout the Journal
J Clin Invest. Sep 1985; 76(3): 1169–1173.
PMCID: PMC424016

Hemoglobin Rahere, a human hemoglobin variant with amino acid substitution at the 2,3-diphosphoglycerate binding site. Functional consequences of the alteration and effects of bezafibrate on the oxygen bindings.


We encountered an abnormal hemoglobin (Rahere), with a threonine residue replacing the beta 82 (EF6) lysine residue at the binding site of 2,3-diphosphoglycerate, which was responsible for overt erythrocytosis in two individuals of a Japanese family. Hemoglobin Rahere shows a lower oxygen affinity on the binding of 2,3-diphosphoglycerate or chloride ions than hemoglobin A. Although a decrease in the positive charge density at the binding sites of 2,3-diphosphoglycerate in hemoglobin Rahere apparently shifts the allosteric equilibrium toward the low affinity state, it greatly diminishes the cofactor effects by anions. The oxygen affinity of the patient's erythrocytes is substantially lowered by the presence of bezafibrate, which combines with sites different from those of 2,3-diphosphoglycerate in either hemoglobin Rahere or hemoglobin A.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (852K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Chanutin A, Curnish RR. Effect of organic and inorganic phosphates on the oxygen equilibrium of human erythrocytes. Arch Biochem Biophys. 1967 Jul;121(1):96–102. [PubMed]
  • Benesch R, Benesch RE. The effect of organic phosphates from the human erythrocyte on the allosteric properties of hemoglobin. Biochem Biophys Res Commun. 1967 Jan 23;26(2):162–167. [PubMed]
  • Perutz MF. Stereochemistry of cooperative effects in haemoglobin. Nature. 1970 Nov 21;228(5273):726–739. [PubMed]
  • Arnone A. X-ray diffraction study of binding of 2,3-diphosphoglycerate to human deoxyhaemoglobin. Nature. 1972 May 19;237(5351):146–149. [PubMed]
  • Lorkin PA, Stephens AD, Beard ME, Wrigley PF, Adams L, Lehmann H. Haemoglobin Rahere (beta Lys-Thr): A new high affinity haemoglobin associated with decreased 2, 3-diphosphoglycerate binding and relative polycythaemia. Br Med J. 1975 Oct 25;4(5990):200–202. [PMC free article] [PubMed]
  • Bonaventura C, Bonaventura J, Amiconi G, Tentori L, Brunori M, Antonini E. Hemoglobin Abruzzo (beta143 (H21) His replaced by Arg). Consequences of altering the 2,3-diphosphoglycerate binding site. J Biol Chem. 1975 Aug 25;250(16):6273–6277. [PubMed]
  • Bonaventura J, Bonaventura C, Sullivan B, Godette G. Hemoglobin Deer Lodge (beta 2 His replaced by Arg). Consequences of altering the 2,3-diphosphoglycerate binding site. J Biol Chem. 1975 Dec 25;250(24):9250–9255. [PubMed]
  • Ikkala E, Koskela J, Pikkarainen P, Rahiala EL, El-Hazmi MA, Nagai K, Lang A, Lehmann H. Hb Helsinki: a variant with a high oxygen affinity and a substitution at a 2,3-DPG binding site (beta82[EF6] Lys replaced by Met). Acta Haematol. 1976;56(5):257–275. [PubMed]
  • Bonaventura J, Bonaventura C, Sullivan B, Ferruzzi G, McCurdy PR, Fox J, Moo-Penn WF. Hemoglobin providence. Functional consequences of two alterations of the 2,3-diphosphoglycerate binding site at position beta 82. J Biol Chem. 1976 Dec 10;251(23):7563–7571. [PubMed]
  • Perutz MF, Poyart C. Bezafibrate lowers oxygen affinity of haemoglobin. Lancet. 1983 Oct 15;2(8355):881–882. [PubMed]
  • Imamura T, Sugihara J, Matsuo T, Maruyama T, Ohta Y, Sumida I, Yamaoka K, Yanase T. Frequency and distribution of structural variants of hemoglobin and thalassemic states in Western Japan. Hemoglobin. 1980;4(3-4):409–415. [PubMed]
  • Schneider RG, Barwick RC. Measuring relative electrophoretic mobilities of mutant hemoglobins and globin chains. Hemoglobin. 1978;2(5):417–435. [PubMed]
  • Hanash SM, Shapiro DN. Separation of human hemoglobins by ion exchange high performance liquid chromatography. Hemoglobin. 1981;5(2):165–175. [PubMed]
  • Abraham EC, Reese A, Stallings M, Huisman TH. Separation of human hemoglobins by DEAE-cellulose chromatography using glycine-KCN-NaC1 developers. Hemoglobin. 1976;1(1):27–44. [PubMed]
  • Clegg JB, Naughton MA, Weatherball DJ. 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. [PubMed]
  • Ericson A, de Verdier CH. A modified method for the determination of 2,3-diphosphoglycerate in erythrocytes. Scand J Clin Lab Invest. 1972 Feb;29(1):84–90. [PubMed]
  • Xchroeder WA, Shelton JB, Shelton JR. Separation of hemoglobin peptides by high performance liquid chromatography (HPLC). Hemoglobin. 1980;4(3-4):551–559. [PubMed]
  • Imai K, Morimoto H, Kotani M, Watari H, Hirata W. Studies on the function of abnormal hemoglobins. I. An improved method for automatic measurement of the oxygen equilibrium curve of hemoglobin. Biochim Biophys Acta. 1970 Feb 17;200(2):189–196. [PubMed]
  • Benesch R, Benesch RE, Yu CI. Reciprocal binding of oxygen and diphosphoglycerate by human hemoglobin. Proc Natl Acad Sci U S A. 1968 Feb;59(2):526–532. [PMC free article] [PubMed]
  • Fermi G. Three-dimensional fourier synthesis of human deoxyhaemoglobin at 2-5 A resolution: refinement of the atomic model. J Mol Biol. 1975 Sep 15;97(2):237–256. [PubMed]
  • Abshagen U, Bablok W, Koch K, Lang PD, Schmidt HA, Senn M, Stork H. Disposition pharmacokinetics of bezafibrate in man. Eur J Clin Pharmacol. 1979 Aug;16(1):31–38. [PubMed]

Articles from The Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • Compound
    PubChem Compound links
  • MedGen
    Related information in MedGen
  • OMIM
    OMIM record citing PubMed
  • PubMed
    PubMed citations for these articles
  • SNP
    PMC to SNP links
  • Substance
    PubChem Substance links

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...