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.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
R.C. Jackson, H.P. Morris, and G. Weber, Neoplastic transformation linked alterations in adenylosuccinate synthetase activity, Biochem. Biophys. Res. Commun. 66: 526 (1975).
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).
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).
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).
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).
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).
J.M. Lowenstein, Ammonia production in muscle and other tissues: the purine nucleotide cycle, Physiol. Rev. 52: 382 (1972).
G. Weber, Biochemical strategy of cancer cells and the design of chemotherapy: G.H.A. Clowes Memorial Lecture, Cancer Res. 43: 3466 (1983).
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).
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).
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).
T. Ikegami, Y. Natsumeda, and G. Weber, Direct assay method for inosine 5′-monophosphate dehydrogenase activity, Anal. Biochem. 150: 155 (1985).
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).
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).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1989 Plenum Press, New York
About this chapter
Cite this chapter
Ikegami, T., Natsumeda, Y., Weber, G. (1989). Isozyme Shift of Adenylosuccinate Synthase in Rat and Human Neoplasms. In: Mikanagi, K., Nishioka, K., Kelley, W.N. (eds) Purine and Pyrimidine Metabolism in Man VI. Advances in Experimental Medicine and Biology, vol 253A. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5673-8_68
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5673-8_68
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5675-2
Online ISBN: 978-1-4684-5673-8
eBook Packages: Springer Book Archive