Qualitative Abnormality of Liver Argininosuccinate Synthetase in a Patient with Citrullinemia

  • Yoshiko Matsuda
  • Akihiko Tsuji
  • Nobuhiko Katunuma
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 153)


The enzymes involved in the urea cycle in normal liver and in the liver of a patient with citrullinemia were compared. The activities of carbamoyl-phosphate synthetase, ornithine-carbamoyl transferase, argininosuccinate synthetase, argininosuccinate lyase, and arginase in the patient’s liver were normal under standard assay conditions. The properties of argininosuccinate synthetase of the patient were compared with those of the enzyme from normal liver. The enzyme from normal liver showed normal Michaelis-Menten kinetics and its Km values for ATP, L-aspartate, and L-citrulline were 1.8 × 10−4 M, 2.9 × 10−5 M, and 3 × 10−5 M, respectively. The enzyme from the patient with citrullinemia also gave hyperbolic curves with respect to the concentrations of ATP and L-aspartate and the Km values for ATP and L-aspartate were 1.8 x 10−4 M and 2.9 × 10−5 M, respectively. However, it gave a sigmoidal curve with respect to the concentration of citrulline, and Hill’s coefficient was 1.66. The molecular weight of argininosuccinate synthetase from both normal liver and the patient’s liver was estimated to be 185,000 by sucrose density gradient centrifugation both in the presence and absence of citrulline. Argininosuccinate stabilized the enzyme preparations from both livers against heat treatment, but the enzyme from the patient’s liver was less stable than the normal enzyme against heat treatment without added argininosuccinate.


Normal Liver Sigmoidal Curve Sucrose Density Gradient Centrifugation Normal Enzyme Argininosuccinate Synthetase 
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  1. 1.
    W. C. McMurray, F. Mohyuddin, R. J. Rossiter, C. Rathbun, G. H. Valentine, S. J. Koegler, and D. E. Zarfas, Citrullinemia, a new amino aciduría associated with mental retardation, Lancet 1: 138 (1962).Google Scholar
  2. 2.
    I. Matsuda, M. Anakura, S. Arashima, Y. Saito, and Y. Oka, A variant form of citrullinemia, J. Ped. 88: 824 (1976).CrossRefGoogle Scholar
  3. T. Saheki, A. Ueda, M. Hosoya, K. Kusumi, S. Takada, M. Tsuda and T. Katsunuma, Qualitative and quantitative abnormalities of argininosuccinate synthetase in citrullinemia, Clin. Chim. Acta 109:325 (1981).Google Scholar
  4. T. A. Tedesco, and W. Mellman, Argininosuccinate synthetase activity and citrulline metabolism in cells cultured from a citrullinemic subject, Proc. Natl. Acad. Sci. U.S.A. 57:829 (1967).Google Scholar
  5. 5.
    D.T. Whelan, T. Brusso, and M. Spate, Citrullinemia: Phenotypic variations, Pediatrics 57: 935 (1976).Google Scholar
  6. N. R. M. Buist, N. G. Kennaway, C. A. Hepburn, J. J. Strandholm, and D. A. Ramberg, Citrullinemia: Investigation and treatment over four year period, J. Ped. 85:208 (1974).Google Scholar
  7. N. G. Kennaway, R. J. Harwood, D. A. Ramberg, R. D. Kolar, and R. M. Buist, Citrullinemia: Enzymatic evidence for genetic heterogeneity, Pediat. Res. 9:554 (1975).Google Scholar
  8. Y. Matsuda, A. Tsuji, N. Katunuma, M. Hayashi, and Y. Takahashi, Studies on liver argininosuccinate synthetase in a patient with citrullinemia and in normal subjects, J. Biochem. 85:191 (1979).Google Scholar
  9. T. Saheki, T. Kusumi, S. Takada, and T. Katsunuma, Studies of rat liver argininosuccinate synthetase. 1. Physicochemical, catalytic and immunochemical properties, J. Biochem. 81:687 (1977).Google Scholar
  10. Rochovansky, H. Kodawaki, and S. Ratner, Biosynthesis of urea, molecular and regulatory properties of crystalline argininosuccinate synthetase, J. Biol. Chem. 252:5287 (1977).Google Scholar
  11. 11.
    W. E. O’Brien, Isolation and characterization of argininosuccinate synthetase from human liver, Biochemistry 18: 5353 (1979).Google Scholar

Copyright information

© Springer Science+Business Media New York 1982

Authors and Affiliations

  • Yoshiko Matsuda
    • 1
  • Akihiko Tsuji
    • 1
  • Nobuhiko Katunuma
    • 1
  1. 1.Department of Enzyme Chemistry, Institute for Enzyme Research, School of MedicineTokushima UniversityTokushima 770Japan

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