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. 1999 Feb 1;337(Pt 3):543–550.

Glutamine synthesis is heterogeneous and differentially regulated along the rabbit renal proximal tubule.

B Ferrier 1, A Conjard 1, M Martin 1, G Baverel 1
PMCID: PMC1220008  PMID: 9895300

Abstract

Glutamine synthesis, a major process for ammonia detoxification and the control of acid-base balance, occurs from various precursors in suspensions of rabbit proximal tubules. However, no data are currently available on the distribution of glutamine synthesis along the rabbit proximal tubule, and its modulation by changes of substrate concentration. Therefore we have microdissected and incubated the three parts (S1, S2 and S3) of rabbit proximal tubules and measured glutamine synthesis from alanine and aspartate. With a physiological concentration of alanine (0.25 mM) or aspartate (0.05 mM), glutamine synthesis in the S1 segment was about half of that in the S2 and S3 segments, and was greater from alanine than from aspartate along the entire proximal tubule. Elevation of alanine and aspartate concentrations to 5 mM increased glutamine synthesis in both a substrate- and segment-dependent manner. It is concluded that glutamine synthesis occurs from alanine and aspartate along the entire rabbit proximal tubule; however, contrary to what might have been expected on the basis of measurement of glutamine synthetase activity, the basal rate of glutamine synthesis and its adaptation to increased substrate availability are heterogeneous along this nephron segment.

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Selected References

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  1. Baverel G., Martin G., Michoudet C. Glutamine synthesis from aspartate in guinea-pig renal cortex. Biochem J. 1990 Jun 1;268(2):437–442. doi: 10.1042/bj2680437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Burch H. B., Choi S., McCarthy W. Z., Wong P. Y., Lowry O. H. The location of glutamine synthetase within the rat and rabbit nephron. Biochem Biophys Res Commun. 1978 May 30;82(2):498–505. doi: 10.1016/0006-291x(78)90902-6. [DOI] [PubMed] [Google Scholar]
  3. Chan A. W., Perry S. G., Burch H. B., Fagioli S., Alvey T. R., Lowry O. H. Distribution of two aminotransferases and D-amino acid oxidase within the nephron of young and adult rats. J Histochem Cytochem. 1979 Mar;27(3):751–755. doi: 10.1177/27.3.39098. [DOI] [PubMed] [Google Scholar]
  4. Chauvin M. F., Megnin-Chanet F., Martin G., Mispelter J., Baverel G. The rabbit kidney tubule simultaneously degrades and synthesizes glutamate. A 13C NMR study. J Biol Chem. 1997 Feb 21;272(8):4705–4716. doi: 10.1074/jbc.272.8.4705. [DOI] [PubMed] [Google Scholar]
  5. Chauvin M. F., Mégnin-Chanet F., Martin G., Lhoste J. M., Baverel G. The rabbit kidney tubule utilizes glucose for glutamine synthesis. A 13C NMR study. J Biol Chem. 1994 Oct 21;269(42):26025–26033. [PubMed] [Google Scholar]
  6. Curthoys N. P., Lowry O. H. Glutamate and glutamine distribution in the rat nephron in acidosis and alkalosis. Am J Physiol. 1973 Apr;224(4):884–889. doi: 10.1152/ajplegacy.1973.224.4.884. [DOI] [PubMed] [Google Scholar]
  7. Forissier M., Baverel G. The conversion of alanine into glutamine in guinea-pig renal cortex. Essential role of pyruvate carboxylase. Biochem J. 1981 Oct 15;200(1):27–33. doi: 10.1042/bj2000027. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Foulkes E. C. Tubular reabsorption delay of amino acids in the rabbit kidney. Am J Physiol. 1985 Dec;249(6 Pt 2):F878–F883. doi: 10.1152/ajprenal.1985.249.6.F878. [DOI] [PubMed] [Google Scholar]
  9. Guder W. G., Ross B. D. Enzyme distribution along the nephron. Kidney Int. 1984 Aug;26(2):101–111. doi: 10.1038/ki.1984.143. [DOI] [PubMed] [Google Scholar]
  10. Höhmann B., Zwiebel R., Yamagata A., Kinne R. Enzymaktivitäten im isolierten proximalen Tubulus der Kaninchenniere. Pflugers Arch. 1969;312(3):110–125. doi: 10.1007/BF00588536. [DOI] [PubMed] [Google Scholar]
  11. Imbert M., Chabardès D., Montégut M., Clique A., Morel F. Adenylate cyclase activity along the rabbit nephron as measured in single isolated segments. Pflugers Arch. 1975;354(3):213–228. doi: 10.1007/BF00584645. [DOI] [PubMed] [Google Scholar]
  12. Janicki R. H., Goldstein L. Glutamine synthetase and renal ammonia metabolism. Am J Physiol. 1969 May;216(5):1107–1110. doi: 10.1152/ajplegacy.1969.216.5.1107. [DOI] [PubMed] [Google Scholar]
  13. Jans A. W., Willem R. A 13C-n.m.r. investigation of the metabolism of amino acids in renal proximal convoluted tubules of normal and streptozotocin-treated rats and rabbits. Biochem J. 1989 Oct 1;263(1):231–241. doi: 10.1042/bj2630231. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kato T., Berger S. J., Carter J. A., Lowry O. H. An enzymatic cycling method for nicotinamide-adenine dinucleotide with malic and alcohol dehydrogenases. Anal Biochem. 1973 May;53(1):86–97. doi: 10.1016/0003-2697(73)90409-0. [DOI] [PubMed] [Google Scholar]
  15. Krebs H. A. Metabolism of amino-acids: The synthesis of glutamine from glutamic acid and ammonia, and the enzymic hydrolysis of glutamine in animal tissues. Biochem J. 1935 Aug;29(8):1951–1969. doi: 10.1042/bj0291951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Kuo C. F., Darnell J. E., Jr Mouse glutamine synthetase is encoded by a single gene that can be expressed in a localized fashion. J Mol Biol. 1989 Jul 5;208(1):45–56. doi: 10.1016/0022-2836(89)90086-7. [DOI] [PubMed] [Google Scholar]
  17. Lemieux G., Baverel G., Vinay P., Wadoux P. Glutamine synthetase and glutamyltransferase in the kidney of man, dog, and rat. Am J Physiol. 1976 Oct;231(4):1068–1073. doi: 10.1152/ajplegacy.1976.231.4.1068. [DOI] [PubMed] [Google Scholar]
  18. Lie-Venema H., de Boer P. A., Moorman A. F., Lamers W. H. Role of the 5' enhancer of the glutamine synthetase gene in its organ-specific expression. Biochem J. 1997 May 1;323(Pt 3):611–619. doi: 10.1042/bj3230611. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lietz T., Bryła J. Glycerol and lactate induce reciprocal changes in glucose formation and glutamine production in isolated rabbit kidney-cortex tubules incubated with aspartate. Arch Biochem Biophys. 1995 Aug 20;321(2):501–509. doi: 10.1006/abbi.1995.1423. [DOI] [PubMed] [Google Scholar]
  20. Magnuson S. R., Young A. P. Murine glutamine synthetase: cloning, developmental regulation, and glucocorticoid inducibility. Dev Biol. 1988 Dec;130(2):536–542. doi: 10.1016/0012-1606(88)90348-x. [DOI] [PubMed] [Google Scholar]
  21. Michoudet C., Martin G., Baverel G. Pyruvate carboxylation in glutamine synthesis from alanine by isolated guinea-pig renal cortical tubules. Pflugers Arch. 1988 Jul;412(1-2):7–11. doi: 10.1007/BF00583724. [DOI] [PubMed] [Google Scholar]
  22. RICHTERICH R. W., GOLDSTEIN L. Distribution of glutamine metabolizing enzymes and production of urinary ammonia in the mammalian kidney. Am J Physiol. 1958 Nov;195(2):316–320. doi: 10.1152/ajplegacy.1958.195.2.316. [DOI] [PubMed] [Google Scholar]
  23. Schmidt U., Horster M. Na-K-activated ATPase: activity maturation in rabbit nephron segments dissected in vitro. Am J Physiol. 1977 Jul;233(1):F55–F60. doi: 10.1152/ajprenal.1977.233.1.F55. [DOI] [PubMed] [Google Scholar]
  24. Schoolwerth A. C., deBoer P. A., Moorman A. F., Lamers W. H. Changes in mRNAs for enzymes of glutamine metabolism in kidney and liver during ammonium chloride acidosis. Am J Physiol. 1994 Sep;267(3 Pt 2):F400–F406. doi: 10.1152/ajprenal.1994.267.3.F400. [DOI] [PubMed] [Google Scholar]
  25. Silbernagl S. The renal handling of amino acids and oligopeptides. Physiol Rev. 1988 Jul;68(3):911–1007. doi: 10.1152/physrev.1988.68.3.911. [DOI] [PubMed] [Google Scholar]
  26. Vandewalle A., Wirthensohn G., Heidrich H. G., Guder W. G. Distribution of hexokinase and phosphoenolpyruvate carboxykinase along the rabbit nephron. Am J Physiol. 1981 Jun;240(6):F492–F500. doi: 10.1152/ajprenal.1981.240.6.F492. [DOI] [PubMed] [Google Scholar]
  27. Zabłocki K., Bryła J. Utilization of alanine for glucose formation in isolated rabbit kidney-cortex tubules. FEBS Lett. 1989 Dec 18;259(1):144–148. doi: 10.1016/0014-5793(89)81514-5. [DOI] [PubMed] [Google Scholar]

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