Regulation of cell growth by 5’-methylthioadenosine

  • Adolph J Ferro
  • Michael K Riscoe
  • Michael W White


The ubiquitous nucleoside 5’-deoxy-5’-methylthioadenosine (MTA) is synthesized from S-adenosylmethionine (SAM) via several metabolic pathways in mammalian cells (Pegg and Hibasami, 1979; Ferro, 1979). MTA, however, does not usually accumulate (normally less than 5 µM, Pegg et al., 1981), but rather is either rapidly degraded to 5-methylthioribose-l-phosphate (MTR-l-P) and adenine by MTA phosphorylase (Pegg and Williams-Ashman, 1969; Garbers, 1978; Ferro et al., 1979) or excreted into the medium in some MTA phosphorylase deficient cell lines (Kamatani and Carson, 1980).


L1210 Cell Lymphocyte Transformation Phosphorylase Activity L12l0 Cell BW5147 Cell 
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  1. Ferro, A. (1979). Function and Metabolism of 5’-Methylthioadenosine. In Transmethylation, eds. E. Usdin, R. Borchardt, and C. Creveling), Elsevier/North-Holland, New York.Google Scholar
  2. Ferro, A. J., Vandenbark, A. A., and MacDonald, M. R. (1981). Inactivation of S-Adenosylhomocysteine Hydrolase by 5’-Deoxy-5’-Methylthioadenosine. Biochem. Biophys. Res. Commun. 100, 523–531.PubMedCrossRefGoogle Scholar
  3. Ferro, A. J., Vandenbark, A. A., and Marchitto, K. (1979). The Role of 5’-Methylthioadenosine Phosphorylase in 5’-Methylthioadenosine-mediated Inhibition of Lymphocyte Transformation. Biochim. Biophys. Acta 588, 294–301.PubMedCrossRefGoogle Scholar
  4. Garbers, D. L. (1978). Demonstration of 5’-Methylthioadenosine Phosphorylase Activity in Various Rat Tissues. Biochim. Biophys. Acta 523, 82–43.Google Scholar
  5. Hibasami, H., Borchardt, R. T., Chen, S. Y., Coward, J. K., and Pegg, A. E. (1980). Studies of Inhibition of Rat Spermidine Synthase and Spermine Synthase. Biochem. J. 187, 419–428.Google Scholar
  6. Kamatani, N. and Carson, D. A. (1980). Abnormal Regulation of Methylthioadenosine and Polyamine Metabolism in Methylthioadenosine Phosphorylase-deficient Human Leukemic Cell Lines. Cancer Res. 40, 4178–4182.Google Scholar
  7. Pegg, A. E., Borchardt, R. T., and Coward, J. K. (1981). Effects of Inhibitors of Spermidine and Spermine Synthesis on Polyamine Concentrations and Growth of Transformed Mouse Fibroblasts. Biochem. J. 194, 79–89.Google Scholar
  8. Pegg, A. E. and Hibasami, H. (1979). The Role of S-Adenosylmethionine in Mammalian Polyamine Synthesis. In Transmethylation, eds. E. Usdin, R. Borchardt, and C. Creveling), Elsevier/North-Holland, New York.Google Scholar
  9. Pegg, A. E. and Williams-Ashman, H. G. (1969). Phosphatestimulated Breakdown of 5’-Methylthioadenosine by Rat Ventral Prostate. Biochem. J. 115, 241–247.Google Scholar
  10. Savarese, T. M., Crabtree, G. W., and Parks, R. E. (1979). Reaction of 5’-Deoxyadenosine and Related Analogs with the 5’-Methyladenosine Cleaving Enzyme of Sarcoma 180 Cells, A Possible Chemotherapeutic Target Enzyme. Biochem. Paramacol. 28, 2227–2230.Google Scholar
  11. Savarese, T. M., Crabtree, G. W., and Parks, R. E. (1981). 5’-Methylthioadenosine Phosphorylase-I. Substrate Activity of 5’-Deoxyadenosine with the Enzyme from Sarcoma 180 Cells. Biochem. Pharmacol. 30, 189–199.Google Scholar
  12. Toohey, J. I. (1977). Methylthio Group Change from Methylthioadenosine. Description of an Enzyme and its Relationship to the Methylthio Requirement of Certain Cells in Culture. Biochem. Biophys. Res. Commun. 78, 1273–1280.Google Scholar
  13. Vandenbark, A. A., Ferro, A. J., and Barney, C. L. Inhibition of lymphocyte transformation by a naturally occurring metabolite: 5’-methylthioadenosine. Cell. Immunol., 49; 26–33, 1980.PubMedCrossRefGoogle Scholar
  14. White, M. W., Vandenbark, A. A., Barney, C. L., and Ferro, A. J. (1981). Structural Analogs of 5’-Methylthioadenosine as Substrates and Inhibitors of 5’-Methylthioadenosine Phosphorylase and as Inhibitors of Human Lymphocyte Transformation. Biochem. Pharmacol., in press.Google Scholar
  15. Williams-Ashman, H. G., Coppoc, G. L., Schenone, A., and Weber, G. (1973). Aspects of Polyamine Biosynthesis in Normal and Malignant Eucaryotic Cells. In Polyamines in Normal and Neoplastic Growth, (ed. D. H. Russell), Raven Press, New York.Google Scholar
  16. Wolford, R. W., MacDonald, M. R., Zehfus, B., Rogers, T. J., and Ferro, A. J. (1981). Effect of 5’-Methylthioadenosine and Its Analogs on Murine Lymphoid Cell Proliferation. Cancer Res. 41, 3035–3039.Google Scholar
  17. Zappia, V., Zydek-Cwick, C. R. and Schlenk, F. (1969). The Specificity of S-Adenosylmethionine Derivatives in Methyl Transfer Reactions. J. Biol. Chem. 244, 4499–4509.PubMedGoogle Scholar

Copyright information

© The contributors 1982

Authors and Affiliations

  • Adolph J Ferro
    • 1
  • Michael K Riscoe
    • 1
  • Michael W White
    • 1
  1. 1.Department of MicrobiologyOregon State UniversityCorvallisUnited States

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