Advertisement

A Mechanism for Valproate-Induced Hyperammonemia

  • F. X. Coudé
  • D. Rabier
  • L. Cathelineau
  • G. Grimber
  • P. Parvy
  • P. Kamoun
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 153)

Abstract

Sodium salt of valproic acid (VPA) is an anticonvulsant which has been successfully used in the treatment of several types of epilepsy, particularly in petit mall. It has been shown recently that VPA induced hyperammonemia in children 2,3. In the search of the mechanism by which VPA inhibits ureagenesis and because of the analogy between some other side effects of VPA and the ketotic hyperglycinemia syndrome (hyperglycinuria 4,5,6 leucopenia 7 and thrombocytopenia 8) we have studied the in vivo and in vitro metabolic effects of VPA on the mitochondrial steps of ureagenesis in rat.

Keywords

Valproic Acid Urea Cycle Sodium Valproate Methylmalonic Acidemia Carbamyl Phosphate Synthetase 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    R. M. Pinder, R. N. Brodgen, T. M. Speight, and G. S. Avery, Sodium valproate: A review of its pharmacological properties and therapeutic efficacy in epilepsy, Drugs 13: 81 (1977).Google Scholar
  2. 2.
    D. Coulter and R. J. Allen, Secondary hyperammonemia: a possible mechanism for valproate encephalopathy, Lancet i: 1310 (1980).Google Scholar
  3. 3.
    J. A. Sius, R. H. Trefor Jones, and W. H. Taylor, Valproate, hyperammonemia and hyperglycinemia, Lancet ii: 260 (1980).Google Scholar
  4. 4.
    P. Kamoun, Ph. Parvy, and P. Debray-Ritzen, Hyperglycinurie induite par le N-dipropylacetate: modéle possible de l’acidemie propionique, Nouv. Pres. Med. 6:2162 (1977).Google Scholar
  5. 5.
    J. Jacken, L. Corbeel, P. Casaer, H. Carchon, L. Eggermond, and R. Eeckeli, Dipropylacetate (valproate) and glycine metabolism, Lancet ii: 8038 (1977).Google Scholar
  6. 6.
    P. Kamoun, and Ph. Parvy, Effet du N-dipropylacetate sur l’élimination urinaire des acides aminés, Hely. Paediatr. Acta 33:373 (1978).Google Scholar
  7. 7.
    L. Boutillier, L. de Lumley, R. Saura and J. Boulesteix, Aplasie medullaire transitoire au cours d’un traitement par le dipropylacetate de sodium, Nouv. Press. Med. 8:611 (1979).Google Scholar
  8. 8.
    D. A. Winfield, P. Benton and M. C. Espir, Sodium valproate and trombocytopenia, Br. Med. J. 2:981 (1976).CrossRefGoogle Scholar
  9. 9.
    G. H. Hogeboom, Fractionation of cell components of animal tissues in:Methods in Enzymology, S. P. Colowick, N. Kaplan eds.: Academic Press, New York (1955).Google Scholar
  10. 10.
    A. J. Meijer and M. Van Voerkom, Control of rate of citrulline synthesis by short term changes in N-acetylglutamate levels in isolated rat liver mitochondria, Febs. Lett. 86:117 (1978).Google Scholar
  11. 11.
    G. Ceriotti and L. Spandrio, Catalytic acceleration of the urea-diacetylmonoxime phenazone-reaction and its application to automatic analysis, Clin. Chem. Acta 11:519 (1965).Google Scholar
  12. 12.
    Fx. Coude, C. Sweetman and W.L. Nyhan, The inhibition by propionyl-CoA of acetylglutamate synthetase in rat liver mitochondria: a possible explanation for hyperammonemia in propionic and methylmalonic acidemia, J. Clin. Invest. 64: 1544 (1979).Google Scholar
  13. 13.
    L. Cathelineau, F. Petit, Fx. Coude, and P. Kamoun, Effect of propionate and pyruvate on citrulline synthesis and ATP content in rat liver mitochondria, Biochem. Biophys. Res. Commun. 90:327 (1979).Google Scholar
  14. 14.
    L. Cathelineau, F. Petit, Ph. Parvy, C. Charpentier, Fx. Coude, J. M. Saudebray and P. Kamoun, Vitamin B12 deficiency in rats and ammonia metabolism in Hommes FA. Ed. Models for the study of Inborn Errors of Metabolism, Elsevier, Amsterdam, (1979).Google Scholar
  15. 15.
    E. Layne, Spectrophotometric and turbidimetric methods for measuring proteins in:Methods in Enzymology, S. P. Colowick and N. 0. Kaplan eds. Academic Press, New York (1957).Google Scholar
  16. 16.
    D. Rabier, L. Cathelineau, P. Briand, and P. Kamoun, Propionate and succinate effects on acetylglutamate biosynthesis by rat liver mitochondria, Biochem. Biophys. Res. Commun. 91:456 (1979).Google Scholar
  17. 17.
    T. Bohmer, The information of propionyl-carnitine in isolated rat liver mitochondria, Biochem. Biophys. Acta, 164:157 (1968).Google Scholar
  18. 18.
    I. Matsumoto, R. Kuhara, and M. Yoshino, Metabolism of branched medium chain length fatty acid. II. é oxidation of sodium dipropylacetate in rats, Biomed. Mass. Spectrom. 3:235 (1976). (1976).Google Scholar
  19. 19.
    J. Koch-Weser and T. R. Browne, Valproic acid, N. Engl. J. Med. 302:661 (1980).Google Scholar
  20. 20.
    M. Tatibana and K. Shigesada, Regulation of urea biosynthesis by the acetylglutamate-arginine system, in: “The Urea Cycle”, S. Grisolia, R. Baguena and F. Mayors eds. J. Wiley and Sons, Inc., New York (1976).Google Scholar
  21. 21.
    S. Grisolia and P. P. Cohen, Catalytic role of glutamate derivatives in citrulline biosynthesis, J. Biol. Chem. 204:753, (1953).Google Scholar
  22. 22.
    S. W. Kim, K. Paik and P. P. Cohen, Ammonia intoxication in rats: protection by N-carbamoyl-L glutamate plus L-Arginine, Proc. Natl. Acad. Sci. USA 69:3530 (1972).Google Scholar
  23. 23.
    Fx. Coude, D. Rabier, L. Cathelineau, G. Grimber, Ph. Parvy and P. Kamoun, Letter to the Editor: A mechanism for valproate-induced hyperammonemia, Pediat. Res. 15:974 (1981).Google Scholar

Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • F. X. Coudé
    • 1
  • D. Rabier
    • 1
  • L. Cathelineau
    • 1
  • G. Grimber
    • 1
  • P. Parvy
    • 1
  • P. Kamoun
    • 1
  1. 1.Laboratoire de Biochimie GénétiqueHôpital des Enfants MaladesParis Cedex 15France

Personalised recommendations