Disposition of Endogenous S-Adenosylhomocysteine and Homocysteine Following Exposure to Nucleoside Analogues and Methotrexate

  • P. M. Ueland
  • A. Svardal
  • H. Refsum.
  • J. R. Lillehaug
  • J-S. Schanche
  • S. Helland
Chapter
Part of the Experimental Biology and Medicine book series (EBAM, volume 12)

Abstract

S-Adenosylhomocysteine (AdoHcy) is a product from and an inhibitor of S-adenosylmethionine-dependent transmethylation reactions. This compound is degraded to adenosine and L-homocysteine (Hcy) in the cell through the action of the enzyme AdoHcy hydrolase (EC 3.3.1.1.) (de la Haba & Cantoni, 1959). The view is held that the AdoHcy hydrolase reaction is the only source of Hcy in vertebrates (Cantoni & Chiang, 1980). Hcy is converted to cystathionine or is salvaged to methionine. In all tissues, except liver and kidney, the latter pathway is catalyzed by a single enzyme, which requires 5-methyl -tetrahydrofolate as methyl donor (Mudd & Levy, 1983). These metabolic relations are depicted in figure 1.

Keywords

Adenosine Methotrexate Folate Methionine Homocysteine 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Aksamit, R.R., Backlund, P.S. and Cantoni, G.L. (1983) J. Biol. Chem. 258, 20–23.PubMedGoogle Scholar
  2. Aksamit, R.R., Falk, W. and Cantoni, G.L. (1982) J. Biol. Chem. 257,. 621–625.PubMedGoogle Scholar
  3. Bartel, R.L. and Borchardt, R.T. (1984) Mol. Pharmacol. 25,. 418–424.PubMedGoogle Scholar
  4. Borchardt, R.T. (1980) J. Med Chem. 23,. 347–356.PubMedCrossRefGoogle Scholar
  5. Borchardt, R.T., Keller, B.T., and Patel-Thombre, U. (1984) J. Biol. Chem. 259,. 4353–4358.PubMedGoogle Scholar
  6. Cantoni, G.L. and Chiang, P.K. (1980) in Natural Sulfur Compounds: Novel Biochemical and Structural Aspects (Cavallini. D., Gaull, G.E., and Zappia, V., Eds.) pp. 67–80, Plenum Press, New York and London.Google Scholar
  7. Carson, D.A., Wasson, D.B., Lakow, E., and Kamatani, N. (1982) Proc. Natl. Acad. Sci. 79. 3848–3852.PubMedCrossRefGoogle Scholar
  8. Chiang, P.K., Guranowski, A. and Segall, J.E. (1981) Arch. Biochem. Biophvs. 207. 175–184.CrossRefGoogle Scholar
  9. Chiang, P.K., Richard, H.H. and Cantoni, G.L. (1977) Mo1. Pharmacol. 13,939–947.Google Scholar
  10. de la Haba, G. and Cantoni, G.L. (1959) J. Biol. Chem. 234,. 603–608.Google Scholar
  11. Garcia-Castro, I., Mato, J.M., Vasanthakumar, G., Wiesmann, W.P., Schiffmann, E. and Chiang, P.K. (1983) J. Biol. Chem. 258. 4345–4349.PubMedGoogle Scholar
  12. German, D.C., Bloch, C.A. and Kredich, N.M. (1983) J. Biol.Chem. 258, 10997–11003.PubMedGoogle Scholar
  13. Glazer, R.I. and Knode, M.C. (1984) J. Biol. Chem. 259,. 12964–12969.PubMedGoogle Scholar
  14. Helland, S. and Ueland, P.M. (1982a) Cancer Res. 42,. 1130–1136.PubMedGoogle Scholar
  15. Helland, S. and Ueland, P.M. (1982b) Cancer Res. 42. 2861–2866.PubMedGoogle Scholar
  16. Helland, S. and Ueland, P.M. (1983) Cancer Res. 43,. 1847–1850.PubMedGoogle Scholar
  17. Hershfield, M.S. (1979) J. Biol. Chem. 254,. 22–25.PubMedGoogle Scholar
  18. Hoffman, J.L. (1980) Arch. Biochem. Biophvs. 205,. 132–135.CrossRefGoogle Scholar
  19. Hoffman, D.R., Marion, D.W., Cornatzer, W.E. and Duerre, J.A. (1980) J. Biol. Chem. 255. 10822–10827.PubMedGoogle Scholar
  20. Houston, D.M., Dolence, E.K., Keller, B.T., Patel-Thombre, U. and Borchardt, R.T. (1985) J. Med. Chem. 28,. 471–477.PubMedCrossRefGoogle Scholar
  21. Jackson, R.C. (1984) Pharmac. Ther. 25,. 61–82.CrossRefGoogle Scholar
  22. Kim, I-K., Aksamit, R.R. and Cantoni, G.L. (1982) J. Biol. Chem. 257,. 14726–14729.PubMedGoogle Scholar
  23. Kim, I-K., Zhang, C-Y., Chiang, P.K. and Cantoni, G.L. (1983) Arch. Biochem. Biophvs. 226,. 65–72.CrossRefGoogle Scholar
  24. Montgomery, J.A., Clayton, S.J., Thomas, H.J., Shannon, W.M., Arnett, G., Bodner, A.J., Kim, I-K., Cantoni, G.L. and Chiang, P.K. (1982) J. Med. Chem. 25, 626–629.PubMedCrossRefGoogle Scholar
  25. Mudd, S.H. and Levy, H.L. (1983) in Metabolic Basis of Inherited Diseases (Standbury, J.B., Ed.) pp. 522–559, McGraw-Hill, New York.Google Scholar
  26. Patel-Thombre, U. and Borchardt, R.T. (1985) Biochemistry 24,. 1130– 1136.PubMedCrossRefGoogle Scholar
  27. Refsum, H., Helland, S. and Ueland, P.M. (1985) Clin. Chem. 31,. 624–628.PubMedGoogle Scholar
  28. Schanche, J-S., Schanche, T. and Ueland, P.M. (1982) Biochim. Biophvs. Acta 721, 399–407.CrossRefGoogle Scholar
  29. Schanche, J-S., Schanche, T., Ueland, P.M., Holy, A. and Votruba, I. (1984a) Mol. Pharmacol. 26,. 553–558.PubMedGoogle Scholar
  30. Schanche, J-S., Schanche, T., Ueland, P.M. and Montgomery, J.A. (1984b) Cancer Res. 44,4297–4302.PubMedGoogle Scholar
  31. Ueland, P.M. (1982) Pharmacol. Rev. 34, 223–253.PubMedGoogle Scholar
  32. Ueland, P.M., Helland, S., Broch, O-J. and Schanche, J-S. (1984) J.Biol. Chem. 259,. 2360–2364.PubMedGoogle Scholar
  33. Ueland,. P.M., Refsum, H., Male, R. and Lillehaug, J.R. (1985) Cancer Res., submitted.Google Scholar
  34. Votruba, I. and Holy, A. (1982) Collect. Czech. Chem. Commun. 47,. 167–172.CrossRefGoogle Scholar
  35. Zimmerman, T.P., Iannone, M. and Wolberg, G. (1984) J. Biol. Chem. 259, 1122–1126.PubMedGoogle Scholar

Copyright information

© The Humana Press Inc. 1986

Authors and Affiliations

  • P. M. Ueland
    • 1
  • A. Svardal
    • 1
  • H. Refsum.
    • 1
  • J. R. Lillehaug
    • 1
  • J-S. Schanche
    • 1
  • S. Helland
    • 1
  1. 1.Clinical Pharmacology Unit, Department of PharmacologyUniversity of BergenBergenNorway

Personalised recommendations