Pflügers Archiv

, Volume 389, Issue 1, pp 61–68 | Cite as

2,3-DPG levels in relation to red cell enzyme activities in rat fetuses and hypoxic newborns

  • Wolfgang Jelkmann
  • Christian Bauer
Heart, Circulation, Respiration and Blood; Environmental and Exercise Physiology


We have measured in red cells from fetal and adult Sprague-Dawley and Wistar rats the activities of phosphofructokinase (PFK), pyruvate kinase (PK) and diphosphoglyceromutase (DPGM) as key enzymes in the regulation of 2,3-diphosphoglycerate (2,3-DPG) levels to gather information on the possible causes of the low concentration of 2,3-DPG in fetal red cells. The most striking differences were seen with regard to PK and DPGM activities. The activity of PK was ten times higher in fetal compared to adult red cells, whereas red cell DPGM activity was absent in fetuses and high in adults. In addition, we studied postnatal changes in red cell PK and DPGM activities as well as in the 2,3-DPG concentration in Sprague-Dawley rats. The concentration of 2,3-DPG and the activity of DPGM in red cells increased to almost the adult value within 2 and 4 weeks after birth, respectively, while the activity of PK decreased concomitantly. The postnatal changes occurred similarly, when newborn rats grew up under conditions of hypoxic hypoxia at 0.46 atm (pO2=9.2 kPa). Our studies support the hypothesis that postnatal changes in 2,3-DPG levels are due to changes in the activity of certain glycolytic enzymes and that the switch from fetal-type to adult-type red cells follows a genetically determined time course.

Key words

Erythrocyte Erythropoiesis Hypoxia Diphosphoglyceric acids Pyruvate kinase Diphosphoglyceromutase Fetus Newborn 


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  1. 1.
    Bartels H (1970) Prenatal respiration. North Holland, AmsterdamGoogle Scholar
  2. 2.
    Bartels H, Bartels R, Rathschlag-Schaefer AM, Röbbel H, Lüdders S (1979) Acclimatization of newborn rats and guineapig to 3,000 to 5,000 m simulated altitudes. Respir Physiol 36:375–389Google Scholar
  3. 3.
    Bauer C, Ludwig I, Ludwig M (1968) Different effects of 2,3-diphosphoglycerate and adenosine triphosphate on the oxygen affinity of adult and foetal human hemoglobin. Life Sci 7:1339–1343Google Scholar
  4. 4.
    Baumann R, Bauer C, Rathschlag-Schaefer AM (1972) Causes of the postnatal decrease of blood oxygen affinity in lambs. Respir Physiol 15:151–158Google Scholar
  5. 5.
    Baumann R, Teischl F, Zoch R, Bartels H (1973) Changes in red cell 2,3-diphosphoglycerate concentration as a cause of the postnatal decrease of pig blood oxygen affinity. Respir Physiol 19:153–161Google Scholar
  6. 6.
    Beutler E (1975) Red cell metabolism. Grune and Stratton, New YorkGoogle Scholar
  7. 7.
    Blunt MH, Kitchens JL, Mayson SM, Huisman THJ (1971) Red cell 2,3-diphosphoglycerate and oxygen affinity in newborn goats and sheep. Proc Soc Exp Biol Med 138:800–803Google Scholar
  8. 8.
    Bowdler AJ, Prankerd TAJ (1964) Studies in congenital nonspherocytic haemolytic anaemias with specific enzyme defects. Acta Haematol 31:65–78Google Scholar
  9. 9.
    Chassin SL, Kruckeberg WC, Brewer GJ (1978) Thermal inactivation differences of phosphofructokinase in erythrocytes from genetically selected high and low DPG rat strains. Biochem Biophys Res Commun 83:1306–1311Google Scholar
  10. 10.
    Cotes PM, Bangham DE (1961) Bioassay of erythropoietin in mice made polycythemic by exposure to air at reduced pressure. Nature 191:1065–1067Google Scholar
  11. 11.
    De Simone J, Biel SI, Heller P (1978) Stimulation of fetal hemoglobin synthesis in baboons by hemolysis and hypoxia. Proc Natl Acad Sci 75:2937–2940Google Scholar
  12. 12.
    Dhindsa DS, Hoversland AS, Templeton JW (1972) Postnatal changes in oxygen affinity and concentrations of 2,3-DPG in dog blood. Biol Neonate 20:226–235Google Scholar
  13. 13.
    Duhm J, Gerlach E (1971) On the mechanisms of the hypoxia-induced increase of 2,3-diphosphoglycerate in erythrocytes. Pflügers Arch 326:254–269Google Scholar
  14. 14.
    Duhm J, Kim HD (1973) Effect of the rapid postnatal increase of 2,3-diphosphoglycerate concentration in erythrocytes on the oxygen affinity of pig blood. In: Gerlach E, Moser K, Deutsch E, Wilmanns W (ed) Erythrocytes, throbocytes, leukocytes. Georg Thieme, Stuttgart, p 164Google Scholar
  15. 15.
    Ericson A, de Verdier CH (1972) A modified method for the determination of 2,3-diphosphoglycerate in erythrocytes. Scand J Clin Lab Invest 29:85–90Google Scholar
  16. 16.
    Garcia JF (1957) Changes in blood, plasma, and red cell volume in the male rat, as a function of age. Am J Physiol 190:19–24Google Scholar
  17. 17.
    Garcia JF (1957) Erythropoietin response to hypoxia as a function of age in the normal male rat. Am J Physiol 190:25–30Google Scholar
  18. 18.
    Harkness DR, Ponce J, Grayson V (1969) A comparative study on the phosphoglyceric acid cycle in mammalian erythrocytes. Comp Biochem Physiol 28:129–138Google Scholar
  19. 19.
    Harkness DR, Isaaks RE, Roth SC (1977) Purification and properties of 2,3-bisphosphoglycerate phosphatase-mutase from erythrocytes of day-old chicks. Eur J Biochem 78:343–351Google Scholar
  20. 20.
    Jacobasch G, Minakami S, Rapoport SM (1974) Glycolysis of the erythrocyte. In: Yoshikawa H, Rapoport SM (eds) Cellular and molecular biology of erythrocytes. Urban & Schwarzenberg. München, p 55Google Scholar
  21. 21.
    Jaworek D, Gruber W, Bergmeyer HU (1974) Adenosin-5′-triphosphat. In: Bergmeyer HU (ed) Methoden der enzymatischen Analyse II. Verlag Chemie. Weinheim/Bergstr, p 2147Google Scholar
  22. 22.
    Jelkmann W, Bauer C (1977) Oxygen affinity and phosphate compounds of red blood cells during intrauterine development of rabbits. Pflügers Arch 372:149–156Google Scholar
  23. 23.
    Jelkmann W, Bauer C (1978) High pyruvate kinase activity causes low concentration of 2,3-diphosphoglycerate in fetal rabbit red cells. Pflügers Arch 375:189–195Google Scholar
  24. 24.
    Jelkmann W, Bauer C (1980) Enzyme activities related to 2,3-P2-glycerate metabolism in embryonic and fetal red cells. Biochem Biophys Res Commun 93:93–99Google Scholar
  25. 25.
    Kitchen H, Brett I (1974) Embryonic and fetal hemoglobin in animals. Ann NY Acad Sci 241:653–671Google Scholar
  26. 26.
    Lahiri S, Brody JS, Motoyama EK, Velasquez TM (1978) Regulation of breathing in newborns at high altitude. J Appl Physiol 44:673–678Google Scholar
  27. 27.
    Lenfant C, Torrance JD, Reynafarje C (1971) Shift of the O2-Hb dissociation curve at altitude: mechanism and effect. J Appl Physiol 30:625–631Google Scholar
  28. 28.
    Mueggler PA, Jones G, Peterson JS, Bissonnette JM, Koler RD, Metcalfe J, Jones RT, Black JA (1980) Postnatal regulation of canine oxygen delivery: erythrocyte components affecting Hb function. Am J Physiol 238:H73-H79Google Scholar
  29. 29.
    Narita H, Ikura K, Yanagawa S, Sasaki R, Chiba H, Saimyoji H, Kumagai N (1980) 2,3-bisphosphoglycerate in developing rabbit erythroid cells. J Biol Chem 255:5230–5235Google Scholar
  30. 30.
    Oswald B, Dassler G (1967) Die Konzentration von Nukleotiden und anderen säurelöslichen P-Verbindungen im Blut der Ratte während der Erythrocytenreifung und-alterung. Acta Biol Med Ger 18:163–175Google Scholar
  31. 31.
    Peterson LL (1978) Red cell diphosphoglycerate mutase. Immunochemical studies in vertebrate cells, including a human variant lacking 2,3-DPG. Blood 52:953–958Google Scholar
  32. 32.
    Petschow R, Petschow D, Bartels R, Baumann R, Bartels H (1978) Regulation of oxygen affinity in blood of fetal, newborn and adult mouse. Respir Physiol 35:271–282Google Scholar
  33. 33.
    Rapoport I, Berger H, Elsner R, Rapoport S (1977) pH-dependent changes of 2,3-bisphosphoglycerate in human red cells during transitional and steady-state in vitro. Eur J Biochem 73:421–427Google Scholar
  34. 34.
    Rosa R, Gaillardon J, Rosa J (1973) Diphosphoglycerate mutase and 2,3-diphosphoglycerate phosphatase activities of red cells: Comparative electrophoretic study. Biochem Biophys Res Commun 51:536–542Google Scholar
  35. 35.
    Rosa R, Prehu M-O, Beuzard Y, Rosa J (1978) The first case of a complete deficiency of diphosphoglycerate mutase in human erythrocytes. J Clin Invest 62:907–915Google Scholar
  36. 36.
    Rose ZB (1970) Enzymes controlling 2,3-diphosphoglycerate in human erythrocytes. Fed Proc 29:1105–1111Google Scholar
  37. 37.
    Stamatoyannopoulos G, Nienhuis AW (1979) (eds) Cellular and molecular regulation of hemoglobin switching. Grune and Stratton. New YorkGoogle Scholar
  38. 38.
    Tobin AJ, Chapman BS, Hansen DA, Lasky L, Selvig SE (1979) Regulation of embryonic and adult hemoglobin synthesis in chickens. In: Stamatoyannopoulos G, Nienhuis AW (eds) Cellular and molecular regulation of hemoglobin switching. Grune and Stratton, New York, p 205Google Scholar
  39. 39.
    Torrance JD (1973) Erythrocyte 2,3-DPG in various mammalian species. In: Gerlach E, Moser K, Moser E, Wilmanns W (eds) Erythrocytes, thrombocytes, leukocytes. Georg Thieme, Stuttgart, p 161Google Scholar
  40. 40.
    Tyuma I, Shimizu K (1969) Different response to organic phosphates of human fetal and adult hemoglobins. Arch Biochem Biophys 129:404–405Google Scholar
  41. 41.
    Wells RMG (1979) Haemoglobin-oxygen affinity in developing embryonic erythroid cells of the mouse. J Comp Physiol 129:333–338Google Scholar
  42. 42.
    Wood WG, Nash J, Weatherall DJ, Robinson JS, Harrison FA (1979) The sheep as an animal model for the switch from fetal to adult hemoglobins. In: Stamatoyannopoulos G, Nienhuis AW (eds) Cellular and molecular regulation of hemoglobin switching. Grune and Stratton, New York, p 153Google Scholar
  43. 43.
    Zanjani ED, Gormus BJ, Bhakthavathsalan A, Engler TM, McHale AP, Mann LI (1979) Effect of thyroid hormone on erythropoiesis and the switch from fetal to adult hemoglobin synthesis in fetal sheep. In: Stamatoyannopoulos G, Nienhuis AW (eds) Cellular and molecular regulation of hemoglobin switching. Grune and Stratton, New York, p 169Google Scholar
  44. 44.
    Zürcher C, Loos JA, Prins HK (1965) Hereditary high ATP content of human erythrocytes. Bibl. Haematol 23:549–556Google Scholar

Copyright information

© Springer-Verlag 1980

Authors and Affiliations

  • Wolfgang Jelkmann
    • 1
  • Christian Bauer
    • 1
  1. 1.Institut für PhysiologieUniversität RegensburgRegesburgGermany

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