Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1972 Jul;69(7):1707–1710. doi: 10.1073/pnas.69.7.1707

Functional Nonequivalence of α and β Hemes in Human Adult Hemoglobin

Ted R Lindstrom 1,2, Chien Ho 1,2,*
PMCID: PMC426783  PMID: 4505648

Abstract

Nuclear magnetic resonance studies of the contact-shifted spectra of heme protons in deoxyhemoglobin A from human adults show conclusively that oxygen binds to the α hemes in preference to the β hemes. The preferential binding is produced in 10% hemoglobin solution at neutral pH by either a 15-fold molar excess of 2,3-diphosphoglycerate or a 5-fold molar excess of inositol hexaphosphate. Preferential binding is not observable in the absence of the organic phosphates. The results indicate that the oxygenation of hemoglobin may be described by a sequential model, or by a concerted model that allows the α hemes to bind ligand first.

Keywords: NMR, preferential ligand binding, organic phosphates, models of cooperative ligand binding

Full text

PDF
1707

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berman M., Benesch R., Benesch R. E. The removal of organic phosphates from hemoglobin. Arch Biochem Biophys. 1971 Jul;145(1):236–239. doi: 10.1016/0003-9861(71)90031-2. [DOI] [PubMed] [Google Scholar]
  2. Cassoly R., Gibson Q. H., Ogawa S., Shulman R. G. Effects of phosphate upon CO binding kinetics and NMR spectra of hemoglobin valency hybrids. Biochem Biophys Res Commun. 1971 Sep;44(5):1015–1021. doi: 10.1016/s0006-291x(71)80187-0. [DOI] [PubMed] [Google Scholar]
  3. Davis D. G., Lindstrom T. R., Mock N. H., Baldassare J. J., Charache S., Jones R. T., Ho C. Nuclear magnetic resonance studies of hemoglobins. VI. Heme proton spectra of human deoxyhemoglobins and their relevance to the nature of co-operative oxygenation of hemoglobin. J Mol Biol. 1971 Aug 28;60(1):101–111. doi: 10.1016/0022-2836(71)90450-5. [DOI] [PubMed] [Google Scholar]
  4. Davis D. G., Mock N. H., Lindstrom T. R., Charache S., Ho C. Nuclear magnetic resonance studies of hemoglobiss. V. The heme proton spectra of human deoxyhemoglobins A, F, Zurich, and Chesapeake. Biochem Biophys Res Commun. 1970 Jul 27;40(2):343–349. doi: 10.1016/0006-291x(70)91015-6. [DOI] [PubMed] [Google Scholar]
  5. Garby L., Gerber G., De Verdier C. H. Binding of 2,3-diphosphoglycerate and adenosine triphosphate to human haemoglobin A. Eur J Biochem. 1969 Aug;10(1):110–115. doi: 10.1111/j.1432-1033.1969.tb00662.x. [DOI] [PubMed] [Google Scholar]
  6. Gray R. D., Gibson Q. H. The binding of carbon monoxide to and chains in tetrameric mammalian hemoglobin. J Biol Chem. 1971 Aug 25;246(16):5176–5178. [PubMed] [Google Scholar]
  7. Haber J. E., Koshland D. E., Jr The effect of 2,3-diphosphoglyceric acid on the changes in - interactions in hemoglobin during oxygenation. J Biol Chem. 1971 Dec 25;246(24):7790–7793. [PubMed] [Google Scholar]
  8. Hopfield J. J., Shulman R. G., Ogawa S. An allosteric model of hemoglobin. I. Kinetics. J Mol Biol. 1971 Oct 28;61(2):425–443. doi: 10.1016/0022-2836(71)90391-3. [DOI] [PubMed] [Google Scholar]
  9. Jänig G. -R., Ruckpaul K., Jung F., Jung W., Grill H. Interaction of haemoglobin with ions binding of inositol hexaphosphate to human haemoglobin a. FEBS Lett. 1971 Oct 1;17(2):173–176. doi: 10.1016/0014-5793(71)80141-2. [DOI] [PubMed] [Google Scholar]
  10. Koshland D. E., Jr, Némethy G., Filmer D. Comparison of experimental binding data and theoretical models in proteins containing subunits. Biochemistry. 1966 Jan;5(1):365–385. doi: 10.1021/bi00865a047. [DOI] [PubMed] [Google Scholar]
  11. Kurland R. J., Little R. G., Davis D. G., Ho C. Proton magnetic resonance study of high- and low-spin hemin derivatives. Biochemistry. 1971 Jun 8;10(12):2237–2246. doi: 10.1021/bi00788a009. [DOI] [PubMed] [Google Scholar]
  12. Linstrom T. R., Olson J. S., Mock N. H., Gibson Q. H., Ho C. Nuclear magnetic resonance studies of hemoglobins. 8. Evidence for preferential ligand binding to chains within deoxyhemoglobins. Biochem Biophys Res Commun. 1971 Oct 1;45(1):22–26. doi: 10.1016/0006-291x(71)90044-1. [DOI] [PubMed] [Google Scholar]
  13. MONOD J., WYMAN J., CHANGEUX J. P. ON THE NATURE OF ALLOSTERIC TRANSITIONS: A PLAUSIBLE MODEL. J Mol Biol. 1965 May;12:88–118. doi: 10.1016/s0022-2836(65)80285-6. [DOI] [PubMed] [Google Scholar]
  14. Ogata R. T., McConnell H. M. Mechanism of cooperative oxygen binding to hemoglobin (spin-labeled triphosphate-concerted transition model-hemoglobin chesapeake). Proc Natl Acad Sci U S A. 1972 Feb;69(2):335–339. doi: 10.1073/pnas.69.2.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ogata R. T., McConnell H. M. The binding of a spin-labeled triphosphate to hemoglobin. Cold Spring Harb Symp Quant Biol. 1972;36:325–336. doi: 10.1101/sqb.1972.036.01.043. [DOI] [PubMed] [Google Scholar]
  16. Ogawa S., Shulman R. G. Observation of allosteric transition in hemoglobin. Biochem Biophys Res Commun. 1971 Jan 8;42(1):9–15. doi: 10.1016/0006-291x(71)90354-8. [DOI] [PubMed] [Google Scholar]
  17. Olson J. S., Gibson Q. H. Organic phosphates and the reaction of N-butyl isocyanide with human hemoglobin. Biochem Biophys Res Commun. 1970 Oct 23;41(2):421–426. doi: 10.1016/0006-291x(70)90521-8. [DOI] [PubMed] [Google Scholar]
  18. Olson J. S., Gibson Q. H. The reaction of n-butyl isocyanide with human hemoglobin. I. Determination of the kinetic parameters involved in the last step in ligand binding. J Biol Chem. 1971 Sep 10;246(17):5241–5253. [PubMed] [Google Scholar]
  19. Perutz M. F. Stereochemistry of cooperative effects in haemoglobin. Nature. 1970 Nov 21;228(5273):726–739. doi: 10.1038/228726a0. [DOI] [PubMed] [Google Scholar]
  20. Riggs A. Mechanism of the enhancement of the Bohr effect in mammalian hemoglobins by diphosphoglycerate. Proc Natl Acad Sci U S A. 1971 Sep;68(9):2062–2065. doi: 10.1073/pnas.68.9.2062. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Tyuma I., Imai K., Shimizu K. Effect of inositol hexaphosphate and other organic phosphates on the cooperativity in oxygen binding of human hemoglobins. Biochem Biophys Res Commun. 1971 Aug 6;44(3):682–686. doi: 10.1016/s0006-291x(71)80137-7. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES