Abstract
GTP has multi-faceted cellular functions. Apart from its role in metabolism, in biosynthesis of RNA, proteins, biopterins, UTP and tubulin, GTP is an intricate part of signal transduction mechanisms, production of c-GMP and adenylates, G-protein action and expression of ras oncogene family. Guanylates are indispensable in DNA biosynthesis, since from GDP dGDP is formed and then dGTP, which is rate-limiting as it is the smallest pool among the dNTPs1,2 (Fig. 1). Curtailing GTP and dGTP pools is an important chemotherapeutic objective. GTP de novo biosynthesis is governed by IMP dehydrogenase (EC 1.1.1.205), the rate-limiting enzyme1,2. GTP pools are influenced by the activity of GPRT (guanine-hypoxanthine phosphoribosyltransferase, EC 2.4.2.8), the salvage enzyme, which can recycle guanine to GMP in one step. The significance of GTP in cancer biochemistry and chemotherapy was highlighted by the discovery that IMP dehydrogenase activity increased in a transformation- and progression-linked fashion in rat hepatomas of different growth rates1,2. IMP dehydrogenase activity increased in all murine and 4 human cancer cell lines and was particularly high in rapidly proliferating neoplastic cells such as leukemic cells1–3.
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© 1991 Plenum Press, New York
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Weber, G. (1991). IMP Dehydrogenase and GTP as Targets in Human Leukemia Treatment. In: Harkness, R.A., Elion, G.B., Zöllner, N. (eds) Purine and Pyrimidine Metabolism in Man VII. Advances in Experimental Medicine and Biology, vol 309B. Springer, New York, NY. https://doi.org/10.1007/978-1-4615-7703-4_64
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DOI: https://doi.org/10.1007/978-1-4615-7703-4_64
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