The American Journal of Digestive Diseases

, Volume 10, Issue 9, pp 814–825 | Cite as

Development of urea-cycle enzymes in the juvenile rat: Effect of long-term administration of L-monosodium glutamate and ammonium acetate

  • Jack H. Hutchinson
  • Daniel H. Labby

Summary and conclusions

Liver urea-cycle enzyme specific activities increase with age and body weight of the developing juvenile rat, with the exception of arginine synthetase. The failure of rat liver arginine synthetase to respond in a similar fashion during the observed growth period is unexplained. Liver carbamyl phosphate synthetase specific activity was markedly and significantly increased during the early oral administration of both Lmonosodium glutamate and ammonium acetate. Prolonged administration of these substances resulted in a return toward control values, indicating adaptation of carbamyl phosphate synthetase to the administered substrates. Liver arginase specific activity was decreased afer 5 weeks of ammonium acetate administration. Liver ornithine transcarbamylase, arginine synthetase, and arginase specific activities did not significantly differ from those of controls during 6 weeks of intragastric L-monosodium glutamate administration.

The induction of rat liver carbamyl phosphate synthetase during L-monosodium glutamate administration suggests a hypothesis for ammonia detoxification not previously considered in the literature. The response of rat liver carbamyl phosphate synthetase is related to current concepts of ammonia intoxication which may occur in human patients with far advanced liver disease.


Ammonium Acetate Arginase Advance Liver Disease Carbamyl Ornithine Transcarbamylase 
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  1. 1.
    Hutchinson, J. H., andLabby, D. H. Studies of rat liver and kidney enzymes. I. Response to massive intragastric doses of chronically administered nitrogenous substances.Am. J. Clin. Nutrition 14:291, 1964.Google Scholar
  2. 2.
    Hutchinson, J. H., andLabby, D. H. Studies of rat liver and kidney enzymes. II. Response to dietary protein deficiency and repletion during chronic administration of ammonium acetate and L-glutamine.Am. J. Clin. Nutrition 14:302, 1964.Google Scholar
  3. 3.
    Koritz, S. B., andCohen, P. P. The effect of diet on citrulline synthesis in vitro.J. Biol. Chem. 200:551, 1952.Google Scholar
  4. 4.
    Labby, D. H., Hutchinson, J. H., Stahl, J., Bockel, R., andImler, M. “Mechanisms of Hepatic Coma.” InBiochemical Clinics: The Liver (Vol. 3). R. H. Donnelley, New York, 1964.Google Scholar
  5. 5.
    Manning, R. T. Ammonia intoxication: The theoretical basis for therapy with arginine.J. Kansas Med. Soc. 58:163, 1957.PubMedGoogle Scholar
  6. 6.
    Walshe, J. M. The effect of glutamic acid in the treatment of hepatic coma.Lancet 1:1075, 1953.PubMedGoogle Scholar
  7. 7.
    McDermott, W. V., Wareham, J., andRiddell, A. G. The treatment of hepatic coma with L-glutamic acid.New England J. Med. 253: 1093, 1955.Google Scholar
  8. 8.
    Webster, L. T., Jr., andDavidson, C. S. Effect of sodium glutamate on hepatic coma.J. Clin. Invest. 35:191, 1956.PubMedGoogle Scholar
  9. 9.
    Iber, F. L., Chalmers, T. C., Stowers, B., Fryar, A., andLink, A. M. Biochemical observations on the use of L-glutamic acid in the treatment of hepatic coma.J. Clin. Invest. 36:106, 1957.Google Scholar
  10. 10.
    Labby, D. H., andHutchinson, J. H. Blood ammonia dynamics in hepatic encephalopathy and the influence of miscellaneous experimental therapy.Clin. Res. 7:118, 1959.Google Scholar
  11. 11.
    Bessman, S. P., andBessman, A. N. The cerebral and peripheral uptake of ammonia in liver disease with an hypothesis for the mechanism of hepatic coma.J. Clin. Invest. 34:622, 1955.PubMedGoogle Scholar
  12. 12.
    Munro, A. F. Nitrogen excretion and arginase activity during amphibian development.Biochem. J. 33:1939, 1957.Google Scholar
  13. 13.
    Brown, G. W., Jr., andCohen, P. P. InSymposium on the Chemical Basis of Development. Ed. by McElroy, W. D. and Glass, B. Johns Hopkins Press, Baltimore, 1958, p. 495.Google Scholar
  14. 14.
    Brown, G. W., Jr., Brown, W. R. andCohen, P. P. Comparative biochemistry of urea synthesis II. Levels of urea cycle enzymes in metamorphosing Rana Catesbeiana tadpoles.J. Biol. Chem. 234:1775, 1959.PubMedGoogle Scholar
  15. 15.
    Dolphin, J. L., andFrieden, E Biochemistry of amphibian metamorphosis II. Arginase activity.J. Biol. Chem. 217:735, 1955.PubMedGoogle Scholar
  16. 16.
    Allison, J. B., Wannemacher, R. W. Jr., Parmer, L. P., andGomez, R. Growth of rats correlated with ribonuclease activity and ribonucleic acid.Fed. Proc. 20:370, 1961.Google Scholar
  17. 17.
    Muramatsu, K., andAshida, K. Effect of dietary protein level on growth and liver enzyme activities of rats.J. Nutrition 76: 143, 1962.Google Scholar
  18. 18.
    Ross, M. H., andBatt, W. G. Diet-age pattern for hepatic enzyme activity.J. Nutrition 61:39, 1957.Google Scholar
  19. 19.
    Barrows, C. H., Jr., andRoeder, L. M. The effect of age on concentrations of enzymes in the livers and kidneys of normal, protein-depleted and protein-repleted rats.Fed. Proc. 20:371, 1961.Google Scholar
  20. 20.
    Jones, M. E., Spector, L., andLipmann, F. J. Carbamyl phosphate, the carbamyl donor in enzymic citrulline synthesis.J. Am. Chem. Soc. 77:819, 1955.Google Scholar
  21. 21.
    Grisolia, S. New developments in carbamyl phosphate and acetyl phosphate metabolism. In Abstracts, Cincinnati, Ohio, Jan. 13–17, 1963, from the American Chemical Society Symposium, Division of Biological Chemistry Abstract No. 81, p. 47 A.Google Scholar
  22. 22.
    Ratner, S., andPetrack, B. Biosynthesis of urea IV. Further studies on condensation in arginine synthesis from citrulline.J. Biol. Chem. 200:161, 1953.PubMedGoogle Scholar
  23. 23.
    Ratner, S., Anslow, W. P., andPetrack, B. Biosynthesis of urea VI. Enzymatic cleavage of argininosuccinic acid to arginine and fumaric acid.J. Biol. Chem. 204: 115, 1953.PubMedGoogle Scholar
  24. 24.
    Archibald, R. M. Determination of citrulline and allantoin and demonstration of citrulline in blood plasma.J. Biol. Chem. 156:121, 1944.Google Scholar
  25. 25.
    Archibald, R. M. InMethods in Enzymology (Vol. 2). Ed. by Colowick, S. P., and Kaplan, N. O., Academic Press, New York, 1955, p. 359.Google Scholar
  26. 26.
    Brown, G. W., andCohen, G. P. Comparative biochemistry of urea synthesis I. Methods for the quantitative assay of the urea cycle enzymes in liver.J. Biol. Chem. 234:1769, 1959.PubMedGoogle Scholar
  27. 27.
    Singh, I. D., Barclay, J. A., andCooke, W. T. Blood ammonia levels in relation to hepatic coma and the administration of glutamic acid.Lancet 1:1004, 1954.Google Scholar
  28. 28.
    Warren, K. S., andShenker, S. Effect of an inhibitor of glutamine synthesis (methionine sulfoximine) on ammonia toxicity and metabolism.J. Lab. Clin. Med. 64:442, 1964.PubMedGoogle Scholar
  29. 29.
    Sherlock, S., Summerskill, W. H. J., White, L. P., andPhear, E. A. Portalsystemic encephalopathy: neurological complications of liver disease.Lancet 2: 453, 1954.Google Scholar
  30. 30.
    Reynolds, T. B., Redeker, A. G., andDavis, P. Controlled study of the effects of L-arginine on hepatic encephalopathy.Am. J. Med. 25:359, 1958.PubMedGoogle Scholar
  31. 31.
    Labby, D. H. and Hutchinson, J. H. Unpublished data.Google Scholar
  32. 32.
    Walshe, J. M. Glutamic acid in hepatic coma.Lancet 1:1235, 1955.Google Scholar
  33. 33.
    Najarian, J. S., andHarper, H. A. A clinical study of the effect of arginine on blood ammonia.Am. J. Med. 21:832, 1956.PubMedGoogle Scholar
  34. 34.
    Davey, M. G. The effect of arginine glutamate on elevated blood ammonia levels in chronic liver disease.Australasian Ann. Med. 13: 72, 1964.Google Scholar
  35. 35.
    Schimke, R. T. Differential effects of fasting and protein free diets on levels of urea cycle enzymes in rat liver.J. Biol. Chem. 237: 1921, 1962.PubMedGoogle Scholar

Copyright information

© Hoeber Medical Division Harper • Harper & Row, Publishers 1965

Authors and Affiliations

  • Jack H. Hutchinson
    • 1
  • Daniel H. Labby
    • 1
  1. 1.From the Metabolic Research Laboratory, and the Department of Medicine, Division of Diabetes and MetabolismUniversity of Oregon Medical SchoolPortland

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