Hormonal regulation of hepatic P-enolpyruvate carboxykinase (GTP) during development

  • Richard W. Hanson
  • Lea Reshef
  • John Ballard
Part of the Faseb Monographs book series (FASEBM, volume 3)


Hepatic gluconeogenesis in the rat does not begin until birth. The enzyme P-enolpyruvate carboxykinase appears initially at birth and is the final enzyme in the gluconeogenic sequence to develop. The appearance of this enzyme in the cytosol of rat liver is caused by the stimulation of enzyme synthesis, probably due directly to an increase in the hepatic concentration of cAMP. Enzyme degradation does not begin until 36 hours after birth. Studies with fetal rats in utero have shown that dibutyryl cAMP or glucagon will stimulate P-enolpyruvate carboxykinase synthesis and that this effect can be blocked by insulin. Insulin is known to depress the synthesis of P-enolpyruvate carboxykinase in adult rat liver and in Reuber H-35 liver cells in culture. The glucocorticoids are without effect on the synthesis of the enzyme in fetal rat liver. Work by Girard et al. (J. Clin. Invest. 52: 3190, 1973) has established that the molar ratio of insulin to glucagon drops from 10 immediately after birth, to 1 after one hour. This is due to both a rise in glucagon and a fall in insulin concentrations at birth. These studies, together with our work on the synthesis of P-enolpyruvate carboxykinase, indicate that the sharp drop in the concentration of insulin may relieve the normal inhibition of enzyme synthesis. This would allow the initial stimulation of enzyme synthesis by the glucagon-mediated rise in the concentration of cAMP.—Hanson, R. W., L. Reshef and J. Ballard. Hormonal regulation of hepatic P-enolpyruvate carboxykinase (GTP) during development. Federation Proc. 34: 166–171, 1975.


Blood Glucose Concentration Enzyme Synthesis Hormonal Regulation Enzyme Degradation Hepatic Gluconeogenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ballard, F. J. Biochem. J 121: 196, 1971.Google Scholar
  2. 2.
    Ballard, F. J., and R. W. Hanson. J. Biol. Chem 244: 5625, 1969.PubMedGoogle Scholar
  3. 3.
    Ballard, F. J., and R. W. Hanson. Biochem. J 104: 866, 1967.PubMedGoogle Scholar
  4. 4.
    Ballard, F. J., and I. T. Oliver. Biochem. Biophys. Acta 71: 578, 1963.PubMedCrossRefGoogle Scholar
  5. 5.
    Bar, H. P., and P. Hahn. Can. J. Biochem 49: 85, 1971.PubMedCrossRefGoogle Scholar
  6. 6.
    Butcher, F. R., and V. R. Potter. Cancer Res. 32: 2141, 1972.PubMedGoogle Scholar
  7. 7.
    Foster, D. O., H. A. Lardy, P. D. Ray and J. B. Johnston. Biochemistry 6: 2120, 1967.PubMedCrossRefGoogle Scholar
  8. 8.
    Girard, J. R., G. S. Cuendet, E. B. Marliss, A. Kervran, M. Rieutort and R. Assan. J. Clin. Invest 52: 3190, 1973.PubMedCrossRefGoogle Scholar
  9. 9.
    Greengard, O. Science 163: 891, 1969.PubMedCrossRefGoogle Scholar
  10. 10.
    Hanson, R. W., L. Fisher, F. J. Ballard and L. Reshef. Enzyme 15: 97, 1974.Google Scholar
  11. 11.
    Hommes, F. A., and A. Beere. Biochim. Biophys. Acta 237: 296, 1971.PubMedCrossRefGoogle Scholar
  12. 12.
    Hopgood, M. F., F. J. Ballard, L. Reshef and R. W. Hanson. Biochem. J 134: 445, 1973.PubMedGoogle Scholar
  13. 13.
    Kenney, F. T. J. Biol. Chem 237: 3495, 1962.PubMedGoogle Scholar
  14. 14.
    Kenney, F. T. J. Biol. Chem 242: 4367, 1967.PubMedGoogle Scholar
  15. 15.
    Nagai, K., and H. Nakagawa. J. Biochem., Tokyo 71: 125, 1972.Google Scholar
  16. 16.
    Nordlie, R. C., and H. A. Lardy. Biochem. Z 338: 356, 1963.Google Scholar
  17. 17.
    Philippidis, H., and F. J. Ballard. Biochem. J 113: 651, 1969.PubMedGoogle Scholar
  18. 18.
    Philippidis, H. A., and F. J. Ballard. Biochem. J 120: 385, 1970.PubMedGoogle Scholar
  19. 19.
    Philippidis, H., R. W. Hanson, L. Reshef, M. Hopgood and F. J. Bal-Lard. Biochem. J 126: 1127, 1972.PubMedGoogle Scholar
  20. 20.
    Ray, P. D., D. O. Foster and H. A. Lardy. J. Biol. Chem 241: 3904, 1966.PubMedGoogle Scholar
  21. 21.
    Reshef, L., F. J. Ballard and R. W. Hanson. J. Biol. Chem 244: 5577, 1969.PubMedGoogle Scholar
  22. 22.
    Reshef, L., and R. W. Hanson. Biochem. J 127: 809, 1972.PubMedGoogle Scholar
  23. 23.
    Schimke, R. T. J. Biol. Chem 239: 3808, 1964.PubMedGoogle Scholar
  24. 24.
    Schimke, R. T., E. W. Sweeny and C. M. Berlin. J. Biol. Chem 240: 322, 1965.PubMedGoogle Scholar
  25. 25.
    Shrago, E., J. W. Young and H. A. Lardy. Science 158: 1527, 1967.CrossRefGoogle Scholar
  26. 26.
    Silpananta, P., and A. G. Goodridge. J. Biol. Chem 246: 5754, 1971.PubMedGoogle Scholar
  27. 27.
    Snell, K., and W. Walker. Biochem. J 132: 739, 1973.PubMedGoogle Scholar
  28. 28.
    Tilghman, S. M., R. W. Hanson, L. Reshef, M. F. Hopgood and F. J. Ballard. Proc. Natl. Acad. Sci. U.S 71: 1304, 1974.CrossRefGoogle Scholar
  29. 29.
    Wicks, W. D., and J. B. MckibbinBiochem. Biophys. Res. Commun. 48: 205, 1972.PubMedCrossRefGoogle Scholar
  30. 30.
    Yeung, D., and I. T. Oliver. Biochem. J 108: 325, 1968.PubMedGoogle Scholar
  31. 31.
    Yeung, D., and I. T. Oliver. Biochemistry 7: 3231, 1968.PubMedCrossRefGoogle Scholar
  32. 32.
    Yeung, D., R. S. Stanley and I. T. Oliver. Biochem. J 105: 1219, 1967.PubMedGoogle Scholar

Copyright information

© Federation of American Societies 1975

Authors and Affiliations

  • Richard W. Hanson
    • 1
    • 2
    • 3
  • Lea Reshef
    • 1
    • 2
    • 3
  • John Ballard
    • 1
    • 2
    • 3
  1. 1.Fels Research Institute and Department of BiochemistryTemple University School of MedicinePhiladelphiaUSA
  2. 2.Department of BiochemistryHebrew University-Hadassah Medical SchoolJerusalemIsrael
  3. 3.Division of Nutritional BiochemistryThe CSIROAdelaideAustralia

Personalised recommendations