Adaptations for Oxygen Transport: Lessons from Fish Hemoglobins

  • R. E. Weber


Hemoglobin (Hb) is a prototype of macromolecules whose functional properties are controlled by ionic effectors and a paradigm for study of the structure, function and allosteric interactions of proteins. By virtue of its well-defined roles in transporting O2 from the respiratory surfaces to the tissues and metabolic end-products such as CO2, protons, heat in the opposite direction, and its implication in regulating other processes in red cells, it forms an ideal model for probing the mechanisms of molecular adaptations to environmental conditions and physiological demands [[16], [62]].


Arctic Charr Bohr Effect Allosteric Effector Root Effect Blood Oxygen Transport 
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  1. 1.
    Bauer C, Forster M, Gros G, Mosca A, Perrella M, Rollema HS, Vogel D (1981) Analysis of bicarbonate binding to crocodilian hemoglobin. J Biol Chem 256:8429–8435PubMedGoogle Scholar
  2. 2.
    Bonaventura C, Bonaventura J (1978) Anionic control of hemoglobin function. In: Caughey WS (ed) Biochemical and clinical aspects of hemoglobin abnormalities. Academic, New York, pp 647–663Google Scholar
  3. 3.
    Brittain T (1987) The Root effect. Comp Biochem Physiol 86B:473–481Google Scholar
  4. 4.
    Brunori M, Coletta M, Giardina B, Wyman J (1978) A macromolecular transducer as illustrated by trout hemoglobin IV. Proc Natl Acad Sci USA 75:4310–4312PubMedCrossRefGoogle Scholar
  5. 5.
    Bunn HF, Ransil BJ, Chao A (1971) The interaction between erythrocyte organic phosphates, magnesium ion, and hemoglobin. J Biol Chem 246:5273–5279PubMedGoogle Scholar
  6. 6.
    Chétrite G, Cassoly R, Chetrite G (1985) Affinity of hemoglobin for the cytoplasmic fragment of human erythrocyte membrane band 3. Equilibrium measurements at physiological pH using matrix-bound proteins: the effects of ionic strength, deoxygenation and of 2,3-diphosphoglycerate. J Mol Biol 185:639–644PubMedCrossRefGoogle Scholar
  7. 7.
    Chien JCW, Mayo KH (1980) Carp hemoglobin. I. Precise oxygen equilibrium and analysis according to the models of Adair and of Monod, Wyman, and Changeux. J Biol Chem 255:9790–9799PubMedGoogle Scholar
  8. 8.
    Davie PS, Wells RMG, Tetens V (1986) Effects of sustained swimming on rainbow trout muscle structure, blood oxygen transport, and lactate dehydrogenase isozymes: evidence for increased aerobic capacity of white muscle. J Exp Zool 237:159–171PubMedCrossRefGoogle Scholar
  9. 9.
    Davis BJ (1991) Developmental changes in the blood oxygen transport system of Kemp’s ridley sea turtle, Lepidochelys kempi. Can J Zool 69:2660–2666CrossRefGoogle Scholar
  10. 10.
    di Prisco G, Tamburrini M (1992) The hemoglobins of marine and freshwater fish: The search for correlations with physiological adaptation. Comp Biochem Physiol [B] 102:661–671Google Scholar
  11. 11.
    Fago A, Carratore V, di Prisco G, Feuerlein RJ, Sottrup-Jensen L, Weber RE (1995) The cathodic hemoglobin of Anguilla anguilla. Amino acid sequence and oxygen equilibria of a reverse Bohr effect hemoglobin with high oxygen affinity and high phosphate sensitivity. J Biol Chem 270:18897–18902PubMedCrossRefGoogle Scholar
  12. 12.
    Fago A, Bendixen E, Malte H, Weber RE (1997) The anodic hemoglobin of Anguilla anguilla. Molecular base for allosteric effects in a Root-effect hemoglobin. J Biol Chem 272:15628–15635PubMedCrossRefGoogle Scholar
  13. 13.
    Fago A, Malte H, Dohn N (1999) Bicarbonate binding to hemoglobin links oxygen and carbon dioxide transport in hagfish. Respir Physiol 115:309–315PubMedCrossRefGoogle Scholar
  14. 14.
    Feuerlein RJ, Weber RE (1996) Oxygen equilibria of cathodic eel hemoglobin analysed in terms of the MWC model and Adair’s successive oxygenation theory. J Comp Physiol 165:597–606Google Scholar
  15. 15.
    Garlick RL, Bunn HF, Fyhn HJ, Fyhn UEH, Martin JP, Noble RW, Powers D (1979) Functional studies on the separated hemoglobin components of an air-breathing catfish, Hoplosternum littorate (Hancock). Comp Biochem Physiol 62A:219–226Google Scholar
  16. 16.
    Giardina B, Messana I, Scatena R, Castagnola M (1995) The multiple functions of hemoglobin. Crit Rev Biochem Mol Biol 30:165–196PubMedCrossRefGoogle Scholar
  17. 17.
    Giles MA, Rystephanuk DM (1989) Ontogenetic variation in the multiple hemoglobins of Arctic charr, Salvelinus alpinus. Can J Fish Aquat Sci 46:804–809CrossRefGoogle Scholar
  18. 18.
    Gillen RG, Riggs A (1973) Structure and function of the isolated hemoglobins of the American eel, Anguilla rostrata. J Biol Chem 248:1961–1969PubMedGoogle Scholar
  19. 19.
    Gronenborn AM, Clore GM, Brunori M, Giardina B, Falcioni G, Perutz MF (1984) Stereochemistry of ATP and GTP bound to fish haemoglobins. A transferred nuclear overhauser enhancement, 31P-Nuclear Magnetic Resonance, oxygen equilibrium and molecular modelling study. J Mol Biol 178:731–742PubMedCrossRefGoogle Scholar
  20. 20.
    Imai K (1982) Allosteric effects in haemoglobin. Cambridge University Press, CambridgeGoogle Scholar
  21. 21.
    Ingermann RL, Terwilliger RC (1981) Intraerythrocytic organic phosphates of fetal and adult seaperch (Embiotoca lateralis): their role in maternal-fetal oxygen transport. J Comp Physiol [B] 144:253–259CrossRefGoogle Scholar
  22. 22.
    Isaacks RE, Kim HD, Harkness DR (1978) Relationship between phosphorylated metabolic intermediates and whole blood oxygen affinity in some air-breathing and water-breathing teleosts. Can J Zool 56:887–890CrossRefGoogle Scholar
  23. 23.
    Jensen FB, Weber RE (1982) Respiratory properties of tench blood and hemoglobin. Adaptation to hypoxic-hypercapnic water. Molec Physiol 2:235–250Google Scholar
  24. 24.
    Jensen FB, Weber RE (1987) Internal hypoxia-hypercapnia in tench exposed to aluminium in acid water: effects on blood gas transport, acid-base status and electrolyte composition in arterial blood. J Exp Biol 127:427–442Google Scholar
  25. 25.
    Jensen FB, Andersen NA, Heisler N (1990) Interrelationships between red cell nucleoside triphosphate content, and blood pH, 02-tension and haemoglobin concentration in carp, Cyprinus carpio. Fish Physiol Biochem 8:459–464CrossRefGoogle Scholar
  26. 26.
    Jensen FB, Fago A, Weber RE (1998) Hemoglobin structure and function. In: Perry SF, Tufts BL (eds) Fish respiration. Academic, San Diego, pp 1–40Google Scholar
  27. 27.
    Jensen FB, Jakobsen MH, Weber RE (1998) Interaction between haemoglobin and synthetic peptides of the N-terminal cytoplasmic Interaction between haemoglobin and synthetic peptides of the N-terminal cytoplasmic fragment of trout band 3 (AE1) protein. J Exp Biol 201:2685–2690PubMedGoogle Scholar
  28. 28.
    Johansen K, Lykkeboe G, Weber RE, Maloiy GMO (1976) Respiratory properties of blood in awake and estivating lungfish, Protopterus amphibius. Respir Physiol 27:335345Google Scholar
  29. 29.
    Johansen K, Mangum CP, Weber RE (1978) Reduced blood 02 affinity associated with air breathing in osteoglossid fishes. Can J Zool 56:891–897CrossRefGoogle Scholar
  30. 30.
    Kleinschmidt T, Sgouros JG (1987) Hemoglobin sequences. Biol Chem Hoppe-Seyler 368:579–615PubMedCrossRefGoogle Scholar
  31. 31.
    Lane HC, Rolfe AE, Nelson JR (1981) Changes in the nucleoside triphosphate/haemoglobin and nucleoside triphosphate/red cell ratios of rainbow trout, Salmo gairdneri Richardson, subjected to prolonged starvation and bleeding. J Fish Biol 18:661–668CrossRefGoogle Scholar
  32. 32.
    Leray C (1979) Patterns of purine necleotides in fish erythrocytes. Comp Biochem Physiol [B] 64B:77–82Google Scholar
  33. 33.
    Leray C (1982) Patterns of purine nucleotides in North Sea fish erythrocytes. Comp Biochem Physiol 71B:77–81Google Scholar
  34. 34.
    Low PS (1986) Structure and function of the cytoplasmic domain of band 3: center of erythrocyte membrane-peripheral protein interactions. Biochim Biophys Acta 864:145–167PubMedCrossRefGoogle Scholar
  35. 35.
    Luisi BF, Nagai K, Perutz M, Perutz MF (1987) X-ray crystallographic and functional studies of human haemoglobin mutants produced in Escherichia coli. Acta Haematol 78:85–89PubMedCrossRefGoogle Scholar
  36. 36.
    Lykkeboe G, Johansen K, Maloiy GMO (1975) Functional properties of hemoglobins in the teleost Tilapia grahami. J Comp Physiol 104:1–11Google Scholar
  37. 37.
    Martin JP, Bonaventura J, Brunori M, Fyhn HJ, Fyhn UEH, Garlick RL, Powers DA, Wilson MT (1979) The isolation and characterization of the hemoglobin components of Mylossoma sp., an Amazonian teleost. Comp Biochem Physiol 62A:155–162Google Scholar
  38. 38.
    Messana I, Orlando M, Cassiano L, Pennacchietti L, Zuppi C, Castagnola M, Giardina B (1996) Human erythrocyte metabolism is modulated by the 02-linked transition of hemoglobin. FEBS Lett 390:25–28PubMedCrossRefGoogle Scholar
  39. 39.
    Moyle PB, Cech JJ Jr (1996) Fishes: an introduction to ichthyology, 3rd edn. Prentice Hall, Upper Saddle RiverGoogle Scholar
  40. 40.
    Mylvaganam SE, Bonaventura C, Bonaventura J, Getzoff ED (1996) Structural basis for the Root effect in haemoglobin. Nature Struct Biol 3:275–283PubMedCrossRefGoogle Scholar
  41. 41.
    Nagai K, Perutz MF, Poyart C (1985) Oxygen binding properties of human mutant hemoglobins synthesized in Escherichia coli. Proc Natl Acad Sci USA 82:7252–7255PubMedCrossRefGoogle Scholar
  42. 42.
    Nikinmaa M (1992) Membrane transport and control of hemoglobin-oxygen affinity in nucleated erythrocytes. Physiol Rev 72:301–321PubMedGoogle Scholar
  43. 43.
    Nikinmaa M, Salama A (1998) Oxygen transport in fish. In: Perry SF, Tufts BL (eds) Fish respiration. Academic, San Diego, pp 141–184Google Scholar
  44. 44.
    Noble RW, Kwiatkowski LD, De Young A, Davis BJ, Haedrich RL, Tam LT, Riggs AF, Tam LT (1986) Functional properties of hemoglobins from deep-sea fish: correlations with depth distribution and presence of a swimbladder. Biochim Biophys Acta 870:552–563PubMedCrossRefGoogle Scholar
  45. 45.
    Perutz MF (1970) Stereochemistry of cooperative effects in haemoglobin. Haemhaem interaction and the problem of allostery. Nature 228:726–734PubMedCrossRefGoogle Scholar
  46. 46.
    Perutz MF (1983) Species adaptation in a protein molecule. Mol Biol Evol 1(1):1–28PubMedGoogle Scholar
  47. 47.
    Perutz MF (1986) A bacterial haemoglobin. Nature 322:405CrossRefGoogle Scholar
  48. 48.
    Perutz MF, Brunori M (1982) Stereochemistry of cooperative effects in fish and amphibian haemoglobins. Nature 299(5882):421–426PubMedCrossRefGoogle Scholar
  49. 49.
    Perutz MF, Fermi G, Poyart C, Pagnier J, Kister J (1993) A novel allosteric mechanism in haemoglobin. Structure of bovine deoxyhaemoglobin, absence of specific chloride-binding sites and origin of the chloride-linked Bohr effect in bovine and human haemoglobin. J Mol Biol 233:536–545PubMedCrossRefGoogle Scholar
  50. 50.
    Samuelsen EN, Imsland AK, Brix 0 (1999) Oxygen binding properties of three different hemoglobin genotypes in turbot (Scophthalmus maximus Rafinesque): effect of temperature and pH. Fish Physiol Biochem 20:135–141CrossRefGoogle Scholar
  51. 51.
    Sayare M, Fikiet M (1981) Cross-linking of hemoglobin to the cytoplasmic surface of human erythrocyte membranes. Identification of band 3 as a site for hemoglobin binding in Cu2+-o-phenanthroline catalyzed cross-linking. J Biol Chem 256:13152–13158PubMedGoogle Scholar
  52. 52.
    Val AL (1993) Adaptations of fishes to extreme conditions in fresh waters. In: Bicudo JEPW (ed) The vertebrate gas transport cascade. Adaptations to environment and mode of life. CRC Press, Boca Raton, pp 43–53Google Scholar
  53. 53.
    Val AL, Schwantes AR, Almeida-Val VMF (1986) Biological aspects of Amazonian fishes VI. Hemoglobins and whole blood properties of Semaprochilodus species (Prochilodontidae) at two phases of migration. Comp Biochem Physiol 83B:659–667Google Scholar
  54. 54.
    Val AL, Affonso EG, Souza RHS, Almeida-Val VMF, Moura MAF (1992) Inositol pentaphosphate in the erythrocytes of an Amazonian fish, the pirarucu (Arapaima gigas). Can J Zool 70:852–855CrossRefGoogle Scholar
  55. 55.
    Vorger P, Ristori M-T (1985) Effects of experimental anemia on the ATP content and the oxygen affinity of the blood in the rainbow trout (Salmo gairdnerii). Comp Biochem Physiol A 82A:221–224CrossRefGoogle Scholar
  56. 56.
    Walder JA, Chatterjee R, Steck TL, Low PS, Musso GF, Kaiser ET, Rogers PH, Arnone A (1984) The interaction of hemoglobin with the cytoplasmic domain of Band 3 of the human erythrocyte membrane. J Biol Chem 259:10238–10246PubMedGoogle Scholar
  57. 57.
    Weber RE (1982) Intraspecific adaptation of hemoglobin function in fish to oxygen availability. In: Addink ADF, Spronk N (eds) Exogenous and endogenous influences on metabolic and neural control, vol 1. Pergamon, Oxford, pp 87–102Google Scholar
  58. 58.
    Weber RE (1990) Functional significance and structural basis of multiple hemoglobins with special reference to ectothermic vertebrates. In: Truchot JP, Lahlou B (eds) Animal nutrition and transport processes. 2. Transport, respiration and excretion: comparative and environmental aspects. Comparative physiology, vol 6, Basel, Karger, pp 58–75Google Scholar
  59. 59.
    Weber RE (1994) Hemoglobin-based 02 transfer in viviparous animals. Isr J Zool 40:541–550Google Scholar
  60. 60.
    Weber RE (1996) Hemoglobin adaptations in Amazonian and temperate fish with special reference to hypoxia, allosteric effectors and functional heterogeneity. In: Val AL, Almeida-Val VMF, Randall DJ (eds) Physiology and biochemistry of the fishes of the Amazon. INPA, Brazil, pp 75–90Google Scholar
  61. 61.
    Weber RE, Hartvig M (1984) Specific fetal hemoglobin underlies the fetal-maternal shift in blood oxygen affinity in a viviparous teleost. Molec Physiol 6:27–32Google Scholar
  62. 62.
    Weber RE, Jensen FB (1988) Functional adaptations in hemoglobins from ectothermic vertebrates. Annu Rev Physiol 50:161–179PubMedCrossRefGoogle Scholar
  63. 63.
    Weber RE, Lykkeboe G (1978) Respiratory adaptations in carp blood. Influences of hypoxia, red cell organic phosphates, divalent cations and CO2 on hemoglobin-oxygen affinity. J Comp Physiol 128B:127–137Google Scholar
  64. 64.
    Weber RE, Wood SC (1979) Effects of erythrocytic nucleoside triphosphates on oxygen equilibria of composite and fractionated hemoglobins from the facultative air-breathing Amazonian catfish, Hypostomus and Pterygoplichthys. Comp Biochem Physiol 62A:179–183Google Scholar
  65. 65.
    Weber RE, Lykkeboe G, Johansen K (1976) Physiological properties of eel haemoglobin: Hypoxic acclimation, phosphate effects and multiplicity. J Exp Biol 64:75–88PubMedGoogle Scholar
  66. 66.
    Weber RE, Wood SC, Davis BJ (1979) Acclimation to hypoxic water in facultative air-breathing fish: Blood oxygen affinity and allosteric effectors. Comp Biochem Physiol 62A:125–129Google Scholar
  67. 67.
    Weber RE, Jensen FB, Cox RP (1987) Analysis of teleost hemoglobin by Adair and Monod-Wyman-Changeux models. Effects of nucleoside triphosphates and pH on oxygenation of tench hemoglobin. J Comp Physiol 157B:145–152Google Scholar
  68. 68.
    Weber RE, Fago A, Val AL, Bang A, Van Hauwaert M-L, Dewilde S, Zal F, Moens L (2000) Isohemoglobin differentiation in the bimodal-breathing Amazon catfish Hoplosternum littorale. J Biol Chem, in pressGoogle Scholar
  69. Wells RMG, Weber RE (1990) The spleen in hypoxic and exercised rainbow trout. J Exp Biol 150:461–466Google Scholar
  70. 70.
    Wilhelm Filho D, Marcon JL, Caprario FX, Correa Nollis A (1992) Erythrocytic nucleoside triphosphates in marine fish. Comp Biochem Physiol A 102A:323–331CrossRefGoogle Scholar
  71. 71.
    Wilkins NP (1985) Ontogeny and evolution of salmonid hemoglobins. Int Rev Cytol 94:269–298PubMedCrossRefGoogle Scholar
  72. 72.
    Wood SC, Johansen K (1972) Adaptation to hypoxia by increased HbO2 affinity and decreased red cell ATP concentration. Nat New Biol 237:278–279PubMedGoogle Scholar
  73. 73.
    Wood SC, Johansen K (1973) Blood oxygen transport and acid-base balance in eels during hypoxia. Am J Physiol 225:849–851PubMedGoogle Scholar
  74. 74.
    Wood SC, Johansen K (1973) Organic phosphate metabolism in nucleated red cells: influence of hypoxia on eel HbO2 affinity. Neth J Sea Res 7:328–338CrossRefGoogle Scholar
  75. 75.
    Yamamoto KI (1988) Contraction of spleen in exercised freshwater teleost. Comp Biochem Physiol A 89:65–66CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Italia 2000

Authors and Affiliations

  • R. E. Weber
    • 1
  1. 1.Center for Respiratory Adaptation (CRA), Department of Zoophysiology, Institute of Biological SciencesUniversity of AarhusAarhusDenmark

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