Advertisement

Metabolite Channelling and Protein—Protein Interactions in the Urea Synthesis Pathway

  • Natalie S. Cohen
  • Chia-Wei Cheung
  • Luisa Raijman
Chapter
Part of the NATO Science Series book series (ASHT, volume 74)

Abstract

The pathway of urea synthesis of mammalian liver has proved to be an excellent model for the investigation of the intracellular organization of soluble enzymes. Studies of the behaviour and regulation of the enzymes of this pathway in situ (reviewed by Cohen et al., 1997) have conclusively shown that the latter operates as a tightly organized system, referred to by Srere (1987), as a metabolon. Intermediates are retained within the pathway and are channelled between sequential enzymes at every step, even across the mitochondrial membranes. By channelled we mean that the intermediates do not mix freely throughout the bulk aqueous phase of the cell.

Keywords

Carbamoyl Phosphate Urea Synthesis Intact Mitochondrion Ornithine Transcarbamylase Carbamyl Phosphate 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Bradford, N. M. & McGivan, J.D. (1980) Evidence for the existence of an ornithine/citrulline antiporter in rat liver mitochondriaFEBS Lett. 113294–298PubMedCrossRefGoogle Scholar
  2. Carey, G. B., Cheung, C.-W., Cohen, N. S., Brusilow, S. & Raijman, L. (1993) Regulation of urea and citrulline synthesis under physiological conditionsBiochem. J. 292241–247Google Scholar
  3. Cheung, C.-W. & Raijman, L. (1981) Arginine, mitochondrial arginase, and the control of carbamyl phosphate synthesisArch. Biochem. Biophys. 209, 643–649PubMedCrossRefGoogle Scholar
  4. Cheung, C.-W., Cohen, N. S. & Raijman, L. (1989) Channeling of urea cycle intermediatesin situin permeabilized hepatocytesJ. Biol. Chem.264, 4038–4044PubMedGoogle Scholar
  5. Clarke, S. (1976) A major polypeptide component of rat liver mitochondria: carbamyl phosphate synthetaseJ. Biol. Chem.251, 950–961PubMedGoogle Scholar
  6. Cohen, N. S. (1996) Intracellular localization of the mRNAs of argininosuccinate synthetase and argininosuccinate lyase around liver mitochondria, visualized byin situreverse transcription-polymerase chain reactionJ. Cell. Biochem. 6181–96PubMedCrossRefGoogle Scholar
  7. Cohen, N. S. & Cheung, C.-W. (1984) Differential effects of N-acetylglutamate on citrulline synthesis by coupled and uncoupled mitochondriaArch. Biochem. Biophys. 23431–44Google Scholar
  8. Cohen, N. S. & Kuda, A. (1996) Argininosuccinate synthetase and argininosuccinate lyase are localized around mitochondria: an immunocytochemical studyJ. Cell. Biochem.60, 334–340Google Scholar
  9. Cohen, N. S., Cheung, C.-W. & Raijman, L. (1980) The effects of ornithine on mitochondrial carbamyl phosphate synthesisJ. Biol. Chem. 25510248–10255PubMedGoogle Scholar
  10. Cohen, N. S., Cheung, C. W., Kyan, F. S., Jones, E. E. & Raijman, L (1982) Mitochondrial carbamyl phosphate and citrulline synthesis at high matrix acetylglutamateJ. Biol. Chem.2576898–6907PubMedGoogle Scholar
  11. Cohen, N. S., Cheung, C.-W., Kyan, F. S., Kyan, S. S. & Raijman, L. (1985) The apparent Kmof ammonia for carbamyl phosphate synthetase (ammonia)in situ Biochem. J. 229205–211PubMedGoogle Scholar
  12. Cohen, N. S., Cheung, C.-W. & Raijman, L. (1987) Channeling of extramitochondrial ornithine to matrix ornithine transcarbamylaseJ. Biol. Chem. 262203–208PubMedGoogle Scholar
  13. Cohen, N. S., Cheung, C.-W., Sijuwade, E. & Raijman, L. (1992) Kinetics of carbamoyl phosphate synthase (ammonia) and ornithine carbamoyltransferase in permeabilized mitochondriaBiochem. J. 282173–180PubMedGoogle Scholar
  14. Cohen, N. S., Cheung, C.-W. & Raijman, L (1997) The urea cycle, pp. 183–199 inChannelling in Intermediary Metabolism(ed. Agius, L. & Sherratt, H. S. A.), Portland Press, LondonGoogle Scholar
  15. Dodgson, S. J., Forster, R. E., II., Schwed, D. A. & Storey, B. T. (1983) Contribution of matrix carbonic anhydrase to citrulline synthesis in isolated guinea pig liver mitochondria J.Biol. Chem. 2587696–7701PubMedGoogle Scholar
  16. Gamble, J. D. & Lehninger, A. L. (1973) Transport of ornithine and citrulline across the mitochondrial membraneJ. Biol. Chem. 248610–618PubMedGoogle Scholar
  17. Glasgow, A. M. & Chase, H. P. (1976) Effect of pent-4-enoic acid, propionic acid and other short-chain fatty acids on citrulline synthesis in rat liver mitochondriaBiochem. J.156, 301–307PubMedGoogle Scholar
  18. Herzfeld, A. & Raper, S. M. (1976) The heterogeneity of arginases in rat tissuesBiochem. J.153,469–478Google Scholar
  19. Jenkinson, C. P., Grody, W. W. & Cederbaum, S. D. (1996) Comparative properties of arginasesComp. Biochem. Physiol. 114107–132CrossRefGoogle Scholar
  20. Krebs, H. A., Hems, R. & Lund, P.(1973) Some regulatory mechanisms in the synthesis of urea in mammalian liverAdv. Enzyme Regul.II, 361–377CrossRefGoogle Scholar
  21. Morris, S. M. Jr. (1992) Regulation of enzymes of urea and arginine synthesis, Annu. Rev.Nutr. 1281–101Google Scholar
  22. Powers-Lee, S. G., Mastico, R. A. & Bendayan, M. (1987) The interaction of rat liver carbamoyl phosphate synthetase and ornithine transcarbamoylase with inner mitochondria) membranes, J.Biol. Chem.262, 15683–15688PubMedGoogle Scholar
  23. Raijman, L. & Bartulis, T. (1979) Effect of ATP translocation on citrulline and oxaloacetate synthesis by isolated rat liver mitochondria, Arch.Biochem. Biophys. 195188–197CrossRefGoogle Scholar
  24. Ratner, S. (1976) The enzymes of arginine and urea synthesisAdv. Enzymol.39, 1–90Google Scholar
  25. Srere, P. A. (1987) Complexes of sequential metabolic enzymesAnnu. Rev. Biochem.56, 89–124PubMedCrossRefGoogle Scholar
  26. Wanders, R. J. A., Van Roermund, C. W. T. & Meijer, A. J. (1984) Analysis of the control of citrulline synthesis in isolated rat-liver mitochondriaEur. J. Biochem. 142247–254PubMedCrossRefGoogle Scholar
  27. Wu, G. & Morris, S. M., Jr. (1998) Arginine metabolism: nitric oxide and beyondBiochem. J. 3361–17PubMedGoogle Scholar
  28. Yokota, S. & Mori, M. (1986) Immunoelectron microscopical localization of ornithine transcarbamylase in hepatic parenchymal cells of the ratHistochem. J.18, 451–457PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2000

Authors and Affiliations

  • Natalie S. Cohen
    • 1
  • Chia-Wei Cheung
    • 2
  • Luisa Raijman
    • 3
  1. 1.Department of Molecular Pharmacology and Toxicology, School of PharmacyUniversity of Southern CaliforniaCaliforniaUSA
  2. 2.Department of Molecular BiologyCity of Hope Beckman Research InstituteCaliforniaUSA
  3. 3.Lafayette HillPennsylvaniaUSA

Personalised recommendations