Isozyme Shift of Adenylosuccinate Synthase in Rat and Human Neoplasms
Adenylosuccinate synthase (EC 18.104.22.168) 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.
KeywordsColon Adenocarcinoma Fumaric Acid Adsorbed Fraction Hepatoma 3924A Adenylosuccinate Lyase
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- 7.J.M. Lowenstein, Ammonia production in muscle and other tissues: the purine nucleotide cycle, Physiol. Rev. 52: 382 (1972).Google Scholar