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. 1980 Apr;17(4):567–571. doi: 10.1128/aac.17.4.567

Inhibition of growth and purine-metabolizing enzymes of trypanosomid flagellates by N6-methyladenine.

L L Nolan, G W Kidder
PMCID: PMC283833  PMID: 6994636

Abstract

N6-methyladenine (6-methylaminopurine [6-MA]), a plant growth regulator and a normal constituent of nucleic acids, has been found to inhibit the growth of Trypanosoma cruzi, Leishmania braziliensis, L. donovani, L. tarentolae, L. mexicana, and Crithidia fasciculata. The extent of growth inhibition in these organisms is related to the sensitivity of guanine deaminase (guanine aminohydrolase, EC 3.5.4.3), adenine deaminase (adenine aminohydrolase, EC 3.5.4.2), and adenosine hydrolase and phosphorylase. 6-MA was not an inhibitor of the purine phosphoribosyltransferases. Of the trypanosomid flagellates tested. Trypanosoma cruzi was most susceptible to 6-MA. Neither adenine deaminase (as found in the leishmaniae and C. fasciculata) nor adenosine deaminase (as found in mammalian cells) could be demonstrated in T. cruzi. Guanine deaminase, which is strikingly inhibited by 6-MA in T. cruzi, appears to play a major role in the purine salvage pathway of this organism, as judged from growth experiments and enzyme inhibition studies. Enzyme sensitivities to 6-MA vary greatly depending upon the organism. Rabbit liver guanine deaminase was shown to be insensitive to 6-MA at the concentrations used in this study.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berens R. L., Brun R., Krassner S. M. A simple monophasic medium for axenic culture of hemoflagellates. J Parasitol. 1976 Jun;62(3):360–365. [PubMed] [Google Scholar]
  2. Dewey V., Kidder G. W. Partial purification and properties of a nucleoside hydrolase from Crithidia. Arch Biochem Biophys. 1973 Aug;157(2):380–387. doi: 10.1016/0003-9861(73)90653-x. [DOI] [PubMed] [Google Scholar]
  3. Gold M., Hurwitz J., Anders M. THE ENZYMATIC METHYLATION OF RNA AND DNA, II. ON THE SPECIES SPECIFICITY OF THE METHYLATION ENZYMES. Proc Natl Acad Sci U S A. 1963 Jul;50(1):164–169. doi: 10.1073/pnas.50.1.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gutteridge W. E., Gaborak M. A re-examination of purine and pyrimidine synthesis in the three main forms of Trypanosoma cruzi. Int J Biochem. 1979;10(5):415–422. doi: 10.1016/0020-711x(79)90065-x. [DOI] [PubMed] [Google Scholar]
  5. Hartenstein R. C., Fridovich I. Adenine aminohydrolase. An investigation of specificity. J Biol Chem. 1967 Feb 25;242(4):740–746. [PubMed] [Google Scholar]
  6. Heinze J. E., Mitani T., Rich K. E., Freese E. Induction of sporulation by inhibitory purines and related compounds. Biochim Biophys Acta. 1978 Nov 21;521(1):16–26. doi: 10.1016/0005-2787(78)90245-9. [DOI] [PubMed] [Google Scholar]
  7. KIDDER G. W., DUTTA B. N. The growth and nutrition of Crithidia fasciculata. J Gen Microbiol. 1958 Jun;18(3):621–638. doi: 10.1099/00221287-18-3-621. [DOI] [PubMed] [Google Scholar]
  8. Kalousek F., Morris N. R. Deoxyribonucleic acid methylase activity in pea seedlings. Science. 1969 May 9;164(3880):721–722. doi: 10.1126/science.164.3880.721. [DOI] [PubMed] [Google Scholar]
  9. Kalousek F., Morris N. R. Deoxyribonucleic acid methylase activity in rat spleen. J Biol Chem. 1968 May 10;243(9):2440–2442. [PubMed] [Google Scholar]
  10. Kalousek F., Morris N. R. The purification and properties of deoxyribonucleic acid methylase from rat spleen. J Biol Chem. 1969 Mar 10;244(5):1157–1163. [PubMed] [Google Scholar]
  11. Keegan F. P., Berech J. The methylated purines of Tetrahymena pyriformis transfer ribonucleic acid. J Protozool. 1979 Aug;26(3):502–504. doi: 10.1111/j.1550-7408.1979.tb04660.x. [DOI] [PubMed] [Google Scholar]
  12. Kidder G. W., Dewey V. C., Nolan L. L. Adenine deaminase of a eukaryotic animal cell, Crithidia fasciculata. Arch Biochem Biophys. 1977 Sep;183(1):7–12. doi: 10.1016/0003-9861(77)90412-x. [DOI] [PubMed] [Google Scholar]
  13. Kidder G. W., Nolan L. L. Adenine aminohydrolase: occurrence and possible significance in trypanosomid flagellates. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3670–3672. doi: 10.1073/pnas.76.8.3670. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. LeJohn H. B., Cameron L. E. Cytokinins regulate calcium binding to a glycoprotein from fungal cells. Biochem Biophys Res Commun. 1973 Oct 1;54(3):1053–1060. doi: 10.1016/0006-291x(73)90800-0. [DOI] [PubMed] [Google Scholar]
  15. Marr J. J., Berens R. L., Nelson D. J. Purine metabolism in Leishmania donovani and Leishmania braziliensis. Biochim Biophys Acta. 1978 Dec 1;544(2):360–371. doi: 10.1016/0304-4165(78)90104-6. [DOI] [PubMed] [Google Scholar]
  16. Sheid B., Srinivasan P. R., Borek E. Deoxyribonucleic acid methylase of mammalian tissues. Biochemistry. 1968 Jan;7(1):280–285. doi: 10.1021/bi00841a034. [DOI] [PubMed] [Google Scholar]
  17. Srinivasan P. R., Borek E. Enzymatic alteration of macromolecular structure. Prog Nucleic Acid Res Mol Biol. 1966;5:157–189. doi: 10.1016/s0079-6603(08)60234-2. [DOI] [PubMed] [Google Scholar]

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