Advertisement

Isozyme Shift of Adenylosuccinate Synthase in Rat and Human Neoplasms

  • Tadashi Ikegami
  • Yutaka Natsumeda
  • George Weber
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 253A)

Abstract

Adenylosuccinate synthase (EC 6.3.4.4) catalyzes the first reaction of AMP biosynthesis at IMP branching point. Previous investigations in this laboratory showed transformation-linked increase of adenylosuccinate synthase activity in rat transplantable hepatomas and kidney tumors. 1, 2 Matsuda et al. separated two isozymes of adenylosuccinate synthase in rat liver and characterized that the acidic isozyme has a lower Km for IMP than the basic isozyme.3 The acidic isozyme was suggested to contribute to purine de novo biosynthesis, since the ratio of the activities of the acidic isozyme to the basic one was increased in the liver of rats fed the purine-free basal diet4 and in regenerating liver5 in which the increased purine de novo synthesis would be required, whereas the basic isozyme was proposed to play a role in purine nucleotide cycle3, 6 involved in ammoniagenesis and regulation of glycolysis.7 These findings directed our attention to the neoplastic expression of the isozyme program of adenylosuccinate synthase in cancer tissues. The present study shows the consistent pattern of the isozyme shift to the acidic adenylosuccinate synthase in rat experimental tumors, human hepatocellular carcinoma and colon adenocarcinoma.

Keywords

Colon Adenocarcinoma Fumaric Acid Adsorbed Fraction Hepatoma 3924A Adenylosuccinate Lyase 
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. 1.
    R.C. Jackson, H.P. Morris, and G. Weber, Neoplastic transformation linked alterations in adenylosuccinate synthetase activity, Biochem. Biophys. Res. Commun. 66: 526 (1975).PubMedCrossRefGoogle Scholar
  2. 2.
    R.C. Jackson, H.P. Morris, and G. Weber, Enzymes of purine nucleotide cycle in rat hepatomas and kidney tumors, Cancer Res. 37: 3057 (1977).PubMedGoogle Scholar
  3. 3.
    Y. Matsuda, H. Ogawa, S. Fukutome, H. Shiraki, and H. Nakagawa, Adenylosuccinate synthetase in rat liver: the existence of two types and their regulatory roles, Biochem. Biophys. Res. Commun. 78: 766 (1977).PubMedCrossRefGoogle Scholar
  4. 4.
    B.W. Baugher, L. Montonaro, M.M. Welch, and F.B. Rudolph, Changes in isozymes of adenylosuccinate synthetase, Biochem. Biophys. Res. Commun. 94: 123 (1980).PubMedCrossRefGoogle Scholar
  5. 5.
    Y. Matsuda, H. Shiraki, H. Ogawa, and H. Nakagawa, Change in content of adenylosuccinate synthetase isozymes during liver regeneration in rats, Biochim. Biophys. Acta 541: 135 (1978).CrossRefGoogle Scholar
  6. 6.
    M.M. Stayton, F.B. Rudolph, and H.J. Fromm, Regulation, genetics, and properties of adenylosuccinate synthetase: a review, Curr. Top. Cell. Regul. 22: 103 (1983).PubMedGoogle Scholar
  7. 7.
    J.M. Lowenstein, Ammonia production in muscle and other tissues: the purine nucleotide cycle, Physiol. Rev. 52: 382 (1972).Google Scholar
  8. 8.
    G. Weber, Biochemical strategy of cancer cells and the design of chemotherapy: G.H.A. Clowes Memorial Lecture, Cancer Res. 43: 3466 (1983).PubMedGoogle Scholar
  9. 9.
    G. Weber, M.E. Burt, R.C. Jackson, N. Prajda, M.S. Lui, and E. Takeda, Purine and pyrimidine enzymic programs and nucleotide pattern in sarcoma, Cancer Res. 43: 1019 (1983).PubMedGoogle Scholar
  10. 10.
    Y. Natsumeda, M.S. Lui, J. Emrani, M.A. Faderan, M.A. Reardon, J.N. Eble, J.L. Glover, and G. Weber, Purine enzymology of human colon carcinomas, Cancer Res. 45: 2556 (1985).PubMedGoogle Scholar
  11. 11.
    Y. Natsumeda, N. Prajda, J.P. Donohue, J.L. Glover, and G. Weber, Enzymic capacities of purine de novo and salvage pathways for nucleotide synthesis in normal and neoplastic tissues, Cancer Res. 44: 2475 (1984).PubMedGoogle Scholar
  12. 12.
    T. Ikegami, Y. Natsumeda, and G. Weber, Direct assay method for inosine 5′-monophosphate dehydrogenase activity, Anal. Biochem. 150: 155 (1985).PubMedCrossRefGoogle Scholar
  13. 13.
    M.N. Goodman and J.M. Lowenstein, The purine nucleotide cycle: studies of ammonia production by skeletal muscle in situ and in perfused preparations, J. Biol. Chem. 252: 5054 (1977).PubMedGoogle Scholar
  14. 14.
    Y. Natsumeda, T. Ikegami, K. Murayama, and G. Weber, De novo guanylate synthesis in the commitment to replication in hepatoma 3924A cells, Cancer Res. 48: 507 (1988).PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1989

Authors and Affiliations

  • Tadashi Ikegami
    • 1
  • Yutaka Natsumeda
    • 1
  • George Weber
    • 1
  1. 1.Laboratory for Experimental OncologyIndiana University School of MedicineIndianapolisUSA

Personalised recommendations