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. 1989 Apr 1;259(1):131–138. doi: 10.1042/bj2590131

Participation of ornithine aminotransferase in the synthesis and catabolism of ornithine in mice. Studies using gabaculine and arginine deprivation.

E Alonso 1, V Rubio 1
PMCID: PMC1138482  PMID: 2497728

Abstract

Gabaculine, a potent suicide inhibitor of ornithine aminotransferase (OAT), at a dose of 50 mg/kg inhibited this enzyme in mouse tissues and dramatically increased tissue ornithine concentrations, whether or not arginine was present in the diet. Thus even under arginine deprivation there is catabolism of ornithine which involves OAT. This was confirmed by administration of [14C]ornithine to arginine-deprived mice. Gabaculine (3-amino-2,3-dihydrobenzoic acid) drastically decreased the release of 14CO2 and increased the radioactivity in the basic amino acids in the tissues. When [1-14C]glutamate was injected into mice deprived of arginine, a significant amount of radioactivity was recovered in tissue ornithine and arginine, and gabaculine decreased this labelling by about two-thirds, indicating that ornithine was synthesized in vivo from glutamate via OAT. In addition, we failed to detect in liver and small intestine alpha-N-acetylornithine, N-acetylglutamate kinase or N-acetylornithine aminotransferase, which are obligatory components of a potential route of ornithine synthesis from N-acetylglutamate. Our results indicate that at least 45 mumol of ornithine was synthesized and catabolized daily via OAT in the mouse deprived of arginine.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alonso E., Rubio V. Binding of N-acetyl-L-glutamate to rat liver carbamoyl phosphate synthetase (ammonia). Eur J Biochem. 1983 Sep 15;135(2):331–337. doi: 10.1111/j.1432-1033.1983.tb07658.x. [DOI] [PubMed] [Google Scholar]
  2. Alonso E., Rubio V. Determination of N-acetyl-L-glutamate using high-performance liquid chromatography. Anal Biochem. 1985 Apr;146(1):252–259. doi: 10.1016/0003-2697(85)90423-3. [DOI] [PubMed] [Google Scholar]
  3. Aniento F., Garcia-España A., Portolés M., Alonso E., Cabo J. R. Effects of inhibition of ornithine aminotransferase or of general aminotransferases on urea and citrulline synthesis and on the levels of acetylglutamate in isolated rat hepatocytes. Mol Cell Biochem. 1988 Feb;79(2):107–112. doi: 10.1007/BF02424551. [DOI] [PubMed] [Google Scholar]
  4. Bell J. M., John A. M. Amino acid requirements of growing mice: arginine, lysine, tryptophan and phenylalanine. J Nutr. 1981 Mar;111(3):525–530. doi: 10.1093/jn/111.3.525. [DOI] [PubMed] [Google Scholar]
  5. Cunin R., Glansdorff N., Piérard A., Stalon V. Biosynthesis and metabolism of arginine in bacteria. Microbiol Rev. 1986 Sep;50(3):314–352. doi: 10.1128/mr.50.3.314-352.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Davis R. H. Compartmental and regulatory mechanisms in the arginine pathways of Neurospora crassa and Saccharomyces cerevisiae. Microbiol Rev. 1986 Sep;50(3):280–313. doi: 10.1128/mr.50.3.280-313.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fukagawa N. K., Minaker K. L., Rowe J. W., Goodman M. N., Matthews D. E., Bier D. M., Young V. R. Insulin-mediated reduction of whole body protein breakdown. Dose-response effects on leucine metabolism in postabsorptive men. J Clin Invest. 1985 Dec;76(6):2306–2311. doi: 10.1172/JCI112240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. GRISOLIA S., COHEN P. P. Catalytic rôle of of glutamate derivatives in citrulline biosynthesis. J Biol Chem. 1953 Oct;204(2):753–757. [PubMed] [Google Scholar]
  9. Gelfand R. A., Barrett E. J. Effect of physiologic hyperinsulinemia on skeletal muscle protein synthesis and breakdown in man. J Clin Invest. 1987 Jul;80(1):1–6. doi: 10.1172/JCI113033. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Greenawalt J. W. The isolation of outer and inner mitochondrial membranes. Methods Enzymol. 1974;31:310–323. doi: 10.1016/0076-6879(74)31033-6. [DOI] [PubMed] [Google Scholar]
  11. Henslee J. G., Jones M. E. Ornithine synthesis from glutamate in rat small intestinal mucosa. Arch Biochem Biophys. 1982 Nov;219(1):186–197. doi: 10.1016/0003-9861(82)90148-5. [DOI] [PubMed] [Google Scholar]
  12. Herzfeld A., Knox W. E. The properties, developmental formation, and estrogen induction of ornithine aminotransferase in rat tissues. J Biol Chem. 1968 Jun 25;243(12):3327–3332. [PubMed] [Google Scholar]
  13. Herzfeld A., Mezl V. A., Knox W. E. Enzymes metabolizing delta1-pyrroline-5-carboxylate in rat tissues. Biochem J. 1977 Jul 15;166(1):95–103. doi: 10.1042/bj1660095. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hoogenraad N., Totino N., Elmer H., Wraight C., Alewood P., Johns R. B. Inhibition of intestinal citrulline synthesis causes severe growth retardation in rats. Am J Physiol. 1985 Dec;249(6 Pt 1):G792–G799. doi: 10.1152/ajpgi.1985.249.6.G792. [DOI] [PubMed] [Google Scholar]
  15. Jung M. J., Seiler N. Enzyme-activated irreversible inhibitors of L-ornithine:2-oxoacid aminotransferase. Demonstration of mechanistic features of the inhibition of ornithine aminotransferase by 4-aminohex-5-ynoic acid and gabaculine and correlation with in vivo activity. J Biol Chem. 1978 Oct 25;253(20):7431–7439. [PubMed] [Google Scholar]
  16. Lund P., Wiggins D. The ornithine requirement of urea synthesis. Formation of ornithine from glutamine in hepatocytes. Biochem J. 1986 Nov 1;239(3):773–776. doi: 10.1042/bj2390773. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Morris C. J., Thompson J. F., Johnson C. M. Metabolism of Glutamic Acid and N-Acetylglutamic Acid in Leaf Discs and Cell-free Extracts of Higher Plants. Plant Physiol. 1969 Jul;44(7):1023–1026. doi: 10.1104/pp.44.7.1023. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Morris J. G. Nutritional and metabolic responses to arginine deficiency in carnivores. J Nutr. 1985 Apr;115(4):524–531. doi: 10.1093/jn/115.4.524. [DOI] [PubMed] [Google Scholar]
  19. Rando R. R., Bangerter F. W. The in vivo inhibition of GABA-transaminase by gabaculine. Biochem Biophys Res Commun. 1977 Jun 20;76(4):1276–1281. doi: 10.1016/0006-291x(77)90993-7. [DOI] [PubMed] [Google Scholar]
  20. Rogers Q. R., Harper A. E. Amino acid diets and maximal growth in the rat. J Nutr. 1965 Nov;87(3):267–273. doi: 10.1093/jn/87.3.267. [DOI] [PubMed] [Google Scholar]
  21. Ross G., Dunn D., Jones M. E. Ornithine synthesis from glutamate in rat intestinal mucosa homogenates: evidence for the reduction of glutamate to gamma-glutamyl semialdehyde. Biochem Biophys Res Commun. 1978 Nov 14;85(1):140–147. doi: 10.1016/s0006-291x(78)80021-7. [DOI] [PubMed] [Google Scholar]
  22. STRECKER H. J. PURIFICATION AND PROPERTIES OF RAT LIVER ORNITHINE DELTA-TRANSAMINASE. J Biol Chem. 1965 Mar;240:1225–1230. [PubMed] [Google Scholar]
  23. Sanada Y., Suemori I., Katunuma N. Properties of ornithine aminotransferase from rat liver, kidney and small intestine. Biochim Biophys Acta. 1970 Oct 14;220(1):42–50. doi: 10.1016/0005-2744(70)90227-5. [DOI] [PubMed] [Google Scholar]
  24. Shigesada K., Aoyagi K., Tatibana M. Role of acetylglutamate in ureotelism. Variations in acetylglutamate level and its possible significance in control of urea synthesis in mammalian liver. Eur J Biochem. 1978 Apr 17;85(2):385–391. doi: 10.1111/j.1432-1033.1978.tb12250.x. [DOI] [PubMed] [Google Scholar]
  25. Shigesada K., Tatibana M. Role of acetylglutamate in ureotelism. I. Occurrence and biosynthesis of acetylglutamate in mouse and rat tissues. J Biol Chem. 1971 Sep 25;246(18):5588–5595. [PubMed] [Google Scholar]
  26. Van Dijk M., Lund P. N-Acetylglutamate in rat liver during foetal development. Biochem J. 1984 Sep 15;222(3):837–838. doi: 10.1042/bj2220837. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Volpe P., Menna T., Pagano G. Ornithine-delta-transaminase heterogeneity and regulation. Sequential expression of the "liver" and "kidney" enzyme forms during the HeLa cell cycle. Eur J Biochem. 1974 May 15;44(2):455–458. doi: 10.1111/j.1432-1033.1974.tb03503.x. [DOI] [PubMed] [Google Scholar]
  28. Volpe P., Sawamura R., Strecker H. J. Control of ornithin delta-transaminase in rat liver and kidney. J Biol Chem. 1969 Feb 25;244(4):719–726. [PubMed] [Google Scholar]
  29. Wakabayashi Y., Henslee J. G., Jones M. E. Pyrroline-5-carboxylate synthesis from glutamate by rat intestinal mucosa. Subcellular localization and temperature stability. J Biol Chem. 1983 Mar 25;258(6):3873–3882. [PubMed] [Google Scholar]
  30. Wakabayashi Y., Jones M. E. Pyrroline-5-carboxylate synthesis from glutamate by rat intestinal mucosa. J Biol Chem. 1983 Mar 25;258(6):3865–3872. [PubMed] [Google Scholar]
  31. Windmueller H. G., Spaeth A. E. Intestinal metabolism of glutamine and glutamate from the lumen as compared to glutamine from blood. Arch Biochem Biophys. 1975 Dec;171(2):662–672. doi: 10.1016/0003-9861(75)90078-8. [DOI] [PubMed] [Google Scholar]
  32. Windmueller H. G., Spaeth A. E. Source and fate of circulating citrulline. Am J Physiol. 1981 Dec;241(6):E473–E480. doi: 10.1152/ajpendo.1981.241.6.E473. [DOI] [PubMed] [Google Scholar]
  33. Wolf E. C., Weiss R. L. Acetylglutamate kinase. A mitochondrial feedback-sensitive enzyme of arginine biosynthesis in Neurospora crassa. J Biol Chem. 1980 Oct 10;255(19):9189–9195. [PubMed] [Google Scholar]

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