Summary
In patients with non-ketotic hyperglycinaemia and two patients with urea cycle disorders treated with varying doses of sodium benzoate there was a linear correlation between intake of benzoate and excretion of hippurate. Patients with non-ketotic hyperglycinaemia excreted significantly more benzoate in the form of hippurate than patients with urea cycle disorders (74 ± 7.0vs 41 ± 3.6%). The plasma concentration of glycine decreased following benzoate treatment only in the patients with non-ketotic hyperglycinaemia. The observed difference between the two groups in the excretion of hippurate seems to support the concept that glycine availability may be limiting in benzoate therapy for some patients.
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References
Arnstein, H. R. V. and Neuberger, A. The synthesis of glycine and serine by the rat.Biochem. J. 55 (1953) 271–280
Bachmann, C. Treatment of congenital hyperammonemias.Enzyme 32 (1984) 56–64
Batshaw, M. L. Sodium benzoate and arginine: Alternative pathway therapy in inborn errors of urea synthesis. In Brewer, G. J. (ed.),Orphan Drugs and Orphan Diseases: Clinical Realities and Public Policy, Liss, New York, 1983, pp. 69–83
Batshaw, M. L. and Brusilow, S. W. Evidence of lack of toxicity of sodium phenylacetate and sodium benzoate in treating urea cycle enzymopathies.J. Inher. Metab. Dis. 4 (1981) 231
Batshaw, M. L., Painter, M. J., Sproul, G. T., Schaffer, I. A., Yhomsd, H. H. and Brusilow, S. Therapy of urea cycle enzymopathies: Three case studies.Johns Hopkins Med. J. 148 (1981) 34–40
Batshaw, M. L., Brusilow, S., Waber, L., Blom, W., Brubakk, A. M., Burton, B. K., Cann, H., Kerr, D., Mamunes, P., Matalon, R., Myerberg, D. and Schafer, I. A. Treatment of inborn errors of urea synthesis. Activation of alternative pathways of waste nitrogen synthesis and excretion.N. Engl. J. Med. 306 (1982) 1387–1392
Baumgartner, R., Ando, T. and Nyhan, W. L. Non-ketotic hyperglycinemia.J. Pediatr. 75 (1969) 1022–1030
Brandt, I. K. Hippurate synthesis in the newborn rat.Am. J. Dis. Child. 100 (1960) 538–539
Brusilow, S., Danney, M., Waber, L. J., Batshaw, M., Burton, B., Levitsky, L., Roth, K., McKeethren, C. and Ward, J. Treatment of episodic hyperammonemia in children with inborn errors of urea synthesis.N. Engl. J. Med. 110 (1984) 1630–1634
Gram, T. E. Metabolism of drugs. In Craig, C. R. and Stitzel, R. E. (eds.),Modern Pharmacology, Little, Boston, 2nd edition, 1986, pp. 50ff
Green, T. P., Marchessault, R. P. and Freese, D. K. Disposition of sodium benzoate in newborn infants with hyperammonemia.J. Pediatr. 102 (1983) 785–790
Kodama, H., Fujiwara, K., Motokawa, Y., Tajiri, H., Nose, O. and Kamoshita, S. Activity of the glycine cleavage system in hyperammonemia treated with benzoate.Tohoku J. Exp. Med. 140 (1983) 337–338
Letarte, J., Quereshi, I. S., Ouellet, R. and Godard, M. Chronic benzoate therapy in a boy with partial ornithine transcarbamylase deficiency.J. Pediatr. 106 (1985) 794–797
Mitch, W. E. and Brusilow, S. Benzoate-induced changes in glycine and urea metabolism in patients with chronic renal failure.J. Pharm. Exp. Ther. 222 (1982) 572–575
Qureshi, I. A., Letarte, J., Ouellet, R., Batshaw, M. L. and Brusilow, S. Treatment of hyperargininemia with sodium benzoate and arginine-restricted diet.J. Pediatr. 104 (1984) 473–476
Shinka, T., Inoue, Y., Kuhara, T., Matsumoto, M. and Matsumoto, I. Benzoylalanine: detection and identification of an alanine conjugate with benzoic acid in hyperammonemia patients treated with sodium benzoate.Clin. Chim. Acta 151 (1985) 293–300
Simkin, J. L. and White, K. The formation of hippuric acid. The influence of benzoate administration on tissue glycine levels.Biochemistry 65 (1957) 574–581
Spackman, D. H., Stein, W. H. and Moore, S. Automatic recording apparatus for use in the chromatography of amino acids.Anal. Chem. 30 (1958) 1190–1206
Sweetman, L. Qualitative and quantitative analysis of organic acids in physiologic fluids for diagnosis of the organic acidurias. In Nyhan, W. L.Abnormalities in Amino Acid Metabolism in Clinical Medicine, Appleton-Century-Crofts, E. Norwalk, Conn., 1984, pp. 419–453
Takeda, S., Kuroda, Y., Toshima, K., Watanabe, T., Naito, E. and Miyao, M. Effect of long-term administration of sodium benzoate to a patient with partial ornithine transcarbamylase deficiency.Clin. Pediatr. 22 (1983) 205–208
Vest, M. F. and Salzberg, R. Conjugation reactions in the newborn infant: The metabolism of para-aminobenzoic acid.Arch. Dis. Child. 40 (1965) 97–105
Weissbach, A. and Sprinson, D. B. The metabolism of 2-carbon compounds related to glycine. I. Glyoxylic acid.J. Biol. Chem. 203 (1953) 1023–1030
Wolff, J. A., Kulovic, S., Yu, A. L., Qiao, Ch-N. and Nyhan, W. L. The effectiveness of benzoate in the management of seizures in nonketotic hyperglycinemia.Am. J. Dis. Child. 140 (1986) 596–602
Ziter, F. A., Bray, P. F., Madsen, J. A. and Nyhan, W. L. The clinical findings in a patient with nonketotic hyperglycinemia.Pediatr. Res. 2 (1968) 250–253
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Barshop, B.A., Breuer, J., Holm, J. et al. Excretion of hippuric acid during sodium benzoate therapy in patients with hyperglycinaemia or hyperammonaemia. J Inherit Metab Dis 12, 72–79 (1989). https://doi.org/10.1007/BF01805533
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DOI: https://doi.org/10.1007/BF01805533