Regulation of Urea Synthesis : Changes in the Concentration of Ornithine in the Liver Corresponding to Changes in Urea Synthesis

  • T. Saheki
  • M. Hosoya
  • S. Fujinami
  • T. Katsunuma
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 153)


The biosynthesis of urea is regulated mainly by two factors, the amounts of urea cycle enzymes and the concentrations of acetyl-glutamate and ornithine. Schimke1 pointed out that the contents of all the urea cycle enzymes in the liver were directly proportional to the daily consumption of protein, then the activities of urea cycle enzymes are an important regulatory factor of the urea cycle. On the other hand, other investigators2–4 reported that the concentration of acetylglutamate, an allosteric activator of carbamylphosphate synthesis, and of ornithine, the rate limiting intermediate, changed under various dietary conditions and suggested that these amino acids play a role in the regulation of urea synthesis. We reported that ornithine and acetylglutamate play a more important role in the regulation of urea synthesis especially shortly after the dietary change. In the liver of rats subjected to acute dietary transitions from high to low protein or vice versa, the concentrations of ornithine and acetylglutamate changed greater and prior to the activity changes of urea cycle enzymes. The rate of urea synthesis from ammonium salt as a substrate were greatly changed in the perfused liver and correlated with the changes in the concentration of ornithine in the liver after the dietary changes5. Arginine derived from dietary protein is thought to be the main source of ornithine and also the cause of changes in acetylglutamate3–5. However, other factors must be involved in the regulation of the concentration of ornithine, since the concentration of orni-thine as well as acetylglutamate increased after the intraperitoneal injection of the ammonium salt without altering either arginine or protein input6.


Basal Diet Ammonium Salt Ammonium Chloride Urea Cycle Dietary Condition 
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  1. 1.
    R.T. Schimke, Adaptive characteristics of urea cycle enzymes in the rat, J. Biol. Chem. 237: 459 (1962).PubMedGoogle Scholar
  2. 2.
    N. Katunuma, M. Okada and Y. Nishii, Regulation of the urea cycle and TCA cycle by ammonia. In: “Advances in Enzyme Regulation”, G. Weber, ed., Pergamon Press, Oxford, 4: 317 (1966).Google Scholar
  3. 3.
    M. Tatibana and K. Shigesada, Regulation of urea biosynthesis by the acetylglutamate-arginine system. In: “The Urea Cycle”, S. Grisolia, R. Baguene and F. Mayor, eds., John-Wiley and Sons, New York, 301 (1976).Google Scholar
  4. 4.
    J.W. Kramer and R. A. Freedland, Possible rate-limiting factors on urea synthesis by the perfused rat liver, Proc. Soc. Exp. Biol. Med., 141: 833 (1972).PubMedGoogle Scholar
  5. 5.
    T. Saheki, T. Katsunuma and M. Sase, Regulation of urea synthesis in rat liver, charges of ornithine and acetylglutamate concentration in the livers of rats subjected to dietary transitions, J. Biochem., 82: 551 (1977).PubMedGoogle Scholar
  6. 6.
    T. Saheki, T. Ohkubo and T. Katsunuma, Regulation of urea synthesis in rat liver, Increase in the concentrations of ornithine and acetylglutamate in rat liver in response to urea synthesis stimulated by the injection of an ammonium salt, J. Biochem. 84: 1423 (1978).PubMedGoogle Scholar
  7. 7.
    M. Walser and L. J. Bodenlos, Urea metabolism in man, J. Clin. Invest. 38: 1 617 (1959).Google Scholar
  8. 8.
    E. A. Jones, R. A. Smallwood, A. Craigle and V. M. Rosenoer, The enterohepatic circulation of urea nitrogen, Clin. Sci. 37: 825 (1969).PubMedGoogle Scholar
  9. 9.
    J.A. Gibson, N.J. Park, G. E. Sladen and A.M. Gawson, The role of the colon in urea metabolism in man, Clin. Sci. Mol. Med. 50: 51 (1976).PubMedGoogle Scholar
  10. 10.
    T. Saheki, A. Ueda, M. Hosoya, T. Katsunuma, N. Ohnishi and A. Oazwa, Comparison of the urea cycle in conventional and germ-free mice. J. Biochem. 88: 1536 (1980).Google Scholar
  11. 11.
    K. Shigesada, K. Aoyagi and M. Tatibana, Role of acetylglutamate in ureotelism. Variation in acetylglutamate level and its possible significance in control of urea synthesis in mammalian liver, Eur. J. Biochem. 85: 385 (1978).PubMedCrossRefGoogle Scholar
  12. 12.
    L.M. Prescott and N.E. Jones, Modified methods for the determination of carbamylaspartate, Anal. Biochem. 32: 408 (1969)Google Scholar
  13. 13.
    O. Rochovansky and S. Ratner, Biosynthesis of urea XII. Further studies on argininosuccinate synthetase: Substrate affinity and mechanism of action, J. Biol. Chem. 242: 3829 (1967)Google Scholar
  14. 14.
    N. Katunuma, Y. Matsuda and I. Tomino, Studies on ornithineketoacid transaminase, J. Biochem. 56: 499 (1964).PubMedGoogle Scholar
  15. 15.
    P.J. Snodgrass and R.C. Lin, Induction of urea cycle enzymes of rat liver by amino acids, J. Nutr. 111: 586 (1981).PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • T. Saheki
    • 1
  • M. Hosoya
    • 2
  • S. Fujinami
    • 2
  • T. Katsunuma
    • 1
  1. 1.Department of Biochemistry, School of MedicineKagoshima UniversityKagoshima, 890Japan
  2. 2.Department of Biochemistry School of MedicineTokai UniversityIseharaJapan

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