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European Journal of Pediatrics

, Volume 146, Issue 1, pp 56–58 | Cite as

Inhibitory effect of intravenous lysine infusion on urea cycle metabolism

  • T. Kato
  • M. Sano
  • N. Mizutani
Original Investigations

Abstract

Intravenous infusion of 0.5 mmol/kgl-lysine monohydrochloride was performed in six normal volunteer subjects aged 10–14 years to study the inhibitory effect of lysine on urea cycle metabolism. The lysine infusion resulted in a significant increase in plasma levels of arginine and ornithine, and in urinary homocitrulline, putrescine, and orotic acid, accompanied by a significant increase in blood ammonia. There was little change in plasma urea and citrulline. The increase in plasma arginine appears to reflect an inhibited arginase activity although the plasma urea level did not change. The increased homocitrulline excretion suggests that ornithine conversion to citrulline via ornithine transcarbamylase (OTC) was inhibited. The simultaneous increase in plasma ornithine and urinary putrescine may reflect an inhibition of mitochondrial ornithine transport. In addition to the direct ammoniagenic property of lysine, impaired ornithine conversion to citrulline resulting from the inhibition of both OTC activity and mitochondrial ornithine uptake by lysine may be responsible for the increase in blood ammonia and urinary orotic acid. Despite the retarded citrulline formation, a promoted efflux of citrulline from mitochondria may have kept the plasma citrulline level unchanged.

Key words

Ammonia Lysine Mitochondrial ornithine transport Ornithine Urea cycle 

Abbreviation

OTC

ornithine transcarbamylase

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References

  1. 1.
    Batshaw ML, Walser M, Brusilow SW (1980) Plasma α-ketoglutarate in urea cycle enzymopathies and its role as a harbinger of hyperammonemic coma. Pediatr Res 14:1316–1319Google Scholar
  2. 2.
    Bradford NM, McGivan JD (1980) Evidence for the existence of an ornithine/citrulline antiporter in rat liver mitochondria. FEBS Lett 113:294–298Google Scholar
  3. 3.
    Cederbaum SD, Shaw KNF, Spector EB, Verity MA, Snodgrass PJ, Sugarman GI (1979) Hyperargininemia with arginase deficiency. Pediatr Res 13:827–833Google Scholar
  4. 4.
    Cittadini D, Pietropaolo C, de Cristofaro D, D'Ayjello-Caracciolo M (1964) In vivo effect ofL-lysine on rat liver arginase. Nature 203:643–644Google Scholar
  5. 5.
    de Vrese M, Barth CA (1985) Influence of lysine on urea cycle activity and orotate formation in the isolated perfused rat liver. Biol Chem Hoppe-Seyler 366:455–461Google Scholar
  6. 6.
    Fico ME, Hassan AS, Milner JA (1982) The influence of excess lysine on urea cycle operation and pyrimidine biosynthesis. J Nutr 112:1854–1861Google Scholar
  7. 7.
    Freedland RA, Crozier GL, Hicks BL, Meijer AJ (1984) Arginine uptake by isolated rat liver mitochondria. Biochim Biophys Acta 802:407–412Google Scholar
  8. 8.
    Hallett CJ, Cook JGH (1971) Reduced nicotinamide adenine dinucleotide-coupled reaction for emergency blood urea estimation. Clin Chim Acta 35:33–37Google Scholar
  9. 9.
    Hommes FA, Kitchings L, Eller AG (1983) The uptake of ornithine and lysine by rat liver mitochondria. Biochem Med 30: 313–321Google Scholar
  10. 10.
    Lusty CJ, Jilka RL, Nietsch EH (1979) Ornithine transcarbamylase of rat liver. Kinetic, physical, and chemical properties. J Biol Chem 254:10030–10036Google Scholar
  11. 11.
    Marton LJ, Russell DH, Levy CC (1973) Measurement of putrescine, spermidine, and spermine in physiological fluids by use of an amino acid analyzer. Clin Chem 19:923–926Google Scholar
  12. 12.
    Persson LO (1981) Decarboxylation of ornithine and lysine by ornithine decarboxylase from kidneys of testosterone treated mice. Acta Chem Scand [B] 35:451–459Google Scholar
  13. 13.
    Ratnaike RN, Buttery JE, Hoffmann S (1984) Blood ammonia measurement using a simple reflectometer. J Clin Chem Clin Biochem 22:105–108Google Scholar
  14. 14.
    Rogers LE, Porter FS (1968) Hereditary orotic aciduria. 11. A urinary screening test. Pediatrics 42:423–428Google Scholar
  15. 15.
    Segal S, Thier SO (1983) Cystinuria. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Brown MS (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 1774–1791Google Scholar
  16. 16.
    Shih VE (1978) Urea cycle disorders and other congenital hyperammonemic syndromes. In: Stanbury JB, Wyngaarden JB, Fredrickson DS (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 362–386Google Scholar
  17. 17.
    Simell O, Luukkainen P, Sipilä I (1985) Alanine-induced hyper-ammonemia in hyperlysinemia and in saccharopinuria. Pediatr Res 19:320AGoogle Scholar
  18. 18.
    Statter M, Russell A (1978) Competitive interrelationships between lysine and arginine in rat liver under normal conditions and in experimental hyperammonemia. Life Sci 22:2097–2102Google Scholar
  19. 19.
    Ulman EA, Kari FW, Hevia P, Visek WJ (1981) Orotic aciduria caused by feeding excess lysine to growing rats. J Nutr 111:1772–1779Google Scholar
  20. 20.
    Valle D, Simell O (1983) The hyperornithinemias. In: Stanbury JB, Wyngaarden JB, Fredrickson DS, Brown MS (eds) The metabolic basis of inherited disease. McGraw-Hill, New York, pp 382–401Google Scholar
  21. 21.
    Zweig JI (1973) Effects of lysine on ammonia formation, hydrogen ion, and potassium ion balance: A review and an hypothesis. Clin Chem 19:943–949Google Scholar

Copyright information

© Springer-Verlag 1987

Authors and Affiliations

  • T. Kato
    • 1
  • M. Sano
    • 1
  • N. Mizutani
    • 2
  1. 1.Department of PediatricsChubu-Rosai HospitalNagoyaJapan
  2. 2.Department of Pediatrics, School of MedicineNagoya UniversityNagoyaJapan

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