PMID: 6108911Oct 1, 1980Paper

Selective guanosine phosphate deficiency in hepatoma cells induced by inhibitors of IMP dehydrogenase

Hoppe-Seyler's Zeitschrift für physiologische Chemie
W A KaiserD O Keppler

Abstract

Inhibition of IMP dehydrogenase in AS-30D hepatoma cells in suspension culture resulted in a pronounced and selective reduction of guanine nucleotide pools. Total acid-soluble guanine nucleotides decreased to 40% and the content of GTP and GDP dropped to about 20% of control within 4 h when mycophenolate or ribavirin were used as the inhibitors. Induction of GTP deficiency was associated with a 50% rise in UTP and other uracil nucleotides. Guanosine rapidly reversed both the reduction of guanine nucleotide pools and the elevation of cellular UTP contents. Enzymatic nucleotide analyses in cell and tissue extracts after treatment with ribavirin indicated that ribavirin 5'-triphosphate was an effective substrate for yeast hexokinase, yeast phosphoglycerate kinase, and nucleosidediphosphate kinase from yeast or bovine liver. These results were confirmed in detail by the use of synthetic ribavirin 5'-triphosphate and 5'-diphosphate. The latter nucleotide analog was also a substrate of pyruvate kinase from muscle. Mycophenolate-induced GTP deficiency was associated with an arrest of hepatoma cell growth in suspension culture. Ribavirin, at an equimolar concentration, was much less effective in this respect. None of the two inhibitors...Continue Reading

References

Jan 1, 1977·Annual Review of Biochemistry·N D Goldberg, M K Haddox
Mar 4, 1977·Annals of the New York Academy of Sciences·J P MillerJ Roboz
Jan 1, 1976·Annual Review of Biochemistry·J A Snyder, J R McIntosh
Jun 1, 1977·Antimicrobial Agents and Chemotherapy·B ErikssonB Oberg
Oct 1, 1977·Journal of Biochemistry·T Arai, Y Kaziro
Jan 1, 1976·Archives of Virology·C Scholtissek
Apr 1, 1973·Proceedings of the National Academy of Sciences of the United States of America·D G StreeterL N Simon

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Citations

Sep 14, 1990·Biochimica Et Biophysica Acta·T Bartel, H G Holzhütter
Jun 10, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·G P IlyinC Guguen-Guillouzo
May 21, 2020·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Xi LinJack Odle

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