Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1983 Aug 1;213(2):495–502. doi: 10.1042/bj2130495

Comparison of inhibitors of S-adenosylmethionine decarboxylase from different species.

A E Pegg, G Jacobs
PMCID: PMC1152153  PMID: 6351843

Abstract

S-Adenosyl-L-methionine decarboxylases were purified from rat ventral prostate, yeast (Saccharomyces cerevisiae), slime mould (Physarum polycephalum) and bacteria (Escherichia coli) and tested for inhibition by a variety of nucleosides related to S-adenosylmethionine and by methyl- and ethyl-glyoxal bis(guanylhydrazone). Although the enzymes from these different sources are markedly different with respect to activation by cations, the inhibition by nucleosides was quite similar. Very little inhibition was seen when analogues of S-adenosylmethionine with a different base were tested or when the ribose ring was opened or the positive charge on the sulphur atom was not present. Some derivatives in which the amino acid portion of the molecule was altered were more potent inhibitors, but again there was little difference between the enzymes from different sources. 5'-(Dimethylsulphonio)-5'-deoxyadenosine and S-adenosyl-3-methylthiopropylamine were the most inhibitory substances and had similar Ki values, suggesting that the aminopropyl group does not contribute significantly to the binding. All of the S-adenosylmethionine decarboxylases were strongly competitively inhibited by methylglyoxal bis(guanylhydrazone) and even more powerfully by its ethyl analogue, although the putrescine-activated enzymes from prostate and yeast were more sensitive than the bacterial and slime-mould enzymes. All of the S-adenosylmethionine decarboxylases tested bound to a column of methylglyoxal bis(guanylhydrazone) linked to Sepharose and were not eluted by 0.5 M-NaCl, but could be released by 1 mM concentrations of the drug, providing a rapid and efficient method for their purification.

Full text

PDF
497

Selected References

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

  1. Allen R. R., Klinman J. P. Stereochemistry and kinetic isotope effects in the decarboxylation of S-adenosylmethionine catalyzed by the pyruvyl enzyme, S-adenosylmethionine decarboxylase. J Biol Chem. 1981 Apr 10;256(7):3233–3239. [PubMed] [Google Scholar]
  2. Borchardt R. T., Shiong Y., Huber J. A., Wycpalek A. F. Potential inhibitors of S-adenosylmethionine-dependent methyltransferases. 6. Structural modifications of S-adenosylmethionine. J Med Chem. 1976 Sep;19(9):1104–1110. doi: 10.1021/jm00231a005. [DOI] [PubMed] [Google Scholar]
  3. Cohn M. S., Tabor C. W., Tabor H. Identification of a pyruvoyl residue in S-adenosylmethionine decarboxylase from Saccharomyces cerevisiae. J Biol Chem. 1977 Nov 25;252(22):8212–8216. [PubMed] [Google Scholar]
  4. Corti A., Dave C., Williams-Ashman H. G., Mihich E., Schenone A. Specific inhibition of the enzymic decarboxylation of S-adenosylmethionine by methylglyoxal bis(guanylhydrazone) and related substances. Biochem J. 1974 May;139(2):351–357. doi: 10.1042/bj1390351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Demetriou A. A., Cohn M. S., Tabor C. W., Tabor H. Identification of pyruvate in S-adenosylmethionine decarboxylase from rat liver. J Biol Chem. 1978 Mar 10;253(5):1684–1686. [PubMed] [Google Scholar]
  6. Heby O., Russell D. H. Effects of methylglyoxal-bis(guanylhydrazone) on polyamine metabolism in spleens of mice with disseminated L1210 lymphoid leukemia. Cancer Res. 1974 Apr;34(4):886–892. [PubMed] [Google Scholar]
  7. Hibasami H., Borchardt R. T., Chen S. Y., Coward J. K., Pegg A. E. Studies of inhibition of rat spermidine synthase and spermine synthase. Biochem J. 1980 May 1;187(2):419–428. doi: 10.1042/bj1870419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hölttä E., Hannonen P., Pispa J., Jänne J. Effect of methylglyoxal bis(guanylhydrazone) on polyamine metabolism in normal and regenerating rat liver and rat thymus. Biochem J. 1973 Nov;136(3):669–676. doi: 10.1042/bj1360669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kolb M., Danzin C., Barth J., Claverie N. Synthesis and biochemical properties of chemically stable product analogues of the reaction catalyzed by S-adenosyl-L-methionine decarboxylase. J Med Chem. 1982 May;25(5):550–556. doi: 10.1021/jm00347a014. [DOI] [PubMed] [Google Scholar]
  10. Markham G. D., Tabor C. W., Tabor H. S-adenosylmethionine decarboxylase of Escherichia coli. Studies on the covalently linked pyruvate required for activity. J Biol Chem. 1982 Oct 25;257(20):12063–12068. [PubMed] [Google Scholar]
  11. Mitchell J. L., Rusch H. P. Regulation of polyamine synthesis in Physarum polyciphalum during growth and differentiation. Biochim Biophys Acta. 1973 Feb 28;297(2):503–516. doi: 10.1016/0304-4165(73)90098-6. [DOI] [PubMed] [Google Scholar]
  12. PODREBARAC E. G., NYBERG W. H., FRENCH F. A., CHENG C. C. STUDIES ON METHYLGLYOXAL BIS(GUANYLHYDRAZONE) ANALOGS. I. HOMOLOGS OF METHYLGLYOXAL BIS(GUANYLHYDRAZONE). J Med Chem. 1963 May;6:283–288. doi: 10.1021/jm00339a014. [DOI] [PubMed] [Google Scholar]
  13. Pankaskie M., Abdel-Monem M. M. Inhibitors of polyamine biosynthesis. 8. Irreversible inhibition of mammalian S-adenosyl-L-methionine decarboxylase by substrate analogues. J Med Chem. 1980 Feb;23(2):121–127. doi: 10.1021/jm00176a004. [DOI] [PubMed] [Google Scholar]
  14. Pegg A. E. Evidence for the presence of pyruvate in rat liver S-adenosylmethionine decarboxylase. FEBS Lett. 1977 Dec 1;84(1):33–36. doi: 10.1016/0014-5793(77)81051-x. [DOI] [PubMed] [Google Scholar]
  15. Pegg A. E. Inhibition of spermidine formation in rat liver and kidney by methylglyoxal bis(guanylhydrazone). Biochem J. 1973 Mar;132(3):537–540. doi: 10.1042/bj1320537. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Pegg A. E. Investigation of the turnover of rat liver S-adenosylmethionine decarboxylase using a specific antibody. J Biol Chem. 1979 May 10;254(9):3249–3253. [PubMed] [Google Scholar]
  17. Pegg A. E., McCann P. P. Polyamine metabolism and function. Am J Physiol. 1982 Nov;243(5):C212–C221. doi: 10.1152/ajpcell.1982.243.5.C212. [DOI] [PubMed] [Google Scholar]
  18. Pegg A. E. Purification of rat liver S-adenosyl-L-methionine decarboxylase. Biochem J. 1974 Aug;141(2):581–583. doi: 10.1042/bj1410581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Pegg A. E. Reactivity of analogues of S-adenosylmethionine in the enzymic synthesis of spermidine by mammalian tissues. Biochim Biophys Acta. 1969 Apr 1;177(2):361–364. [PubMed] [Google Scholar]
  20. Pegg A. E., Williams-Ashman H. G. On the role of S-adenosyl-L-methionine in the biosynthesis of spermidine by rat prostate. J Biol Chem. 1969 Feb 25;244(4):682–693. [PubMed] [Google Scholar]
  21. Porta R., Esposito C., Pietra G. D. S-adenosylmethionine decarboxylase from human placenta. Int J Biochem. 1977;8(5):347–352. doi: 10.1016/0020-711x(77)90003-9. [DOI] [PubMed] [Google Scholar]
  22. Pösö H., Hannonen P., Himberg J. J., Jänne J. Adenosylmethionine decarboxylase from various organisms: relation of the putrescine activation of the enzyme to the ability of the organism to synthesize spermine. Biochem Biophys Res Commun. 1976 Jan 12;68(1):227–234. doi: 10.1016/0006-291x(76)90033-4. [DOI] [PubMed] [Google Scholar]
  23. Pösö H., Pegg A. E. Comparison of S-adenosylmethionine decarboxylases from rat liver and muscle. Biochemistry. 1982 Jun 22;21(13):3116–3122. doi: 10.1021/bi00256a013. [DOI] [PubMed] [Google Scholar]
  24. Pösö H., Sinervirta R., Himberg J. J., Jänne J. Putrescine-insensitive S-adenosyl-L-methionine decarboxylase from Tetrahymena pyriformis. Acta Chem Scand B. 1975;29(9):932–936. doi: 10.3891/acta.chem.scand.29b-0932. [DOI] [PubMed] [Google Scholar]
  25. Sakai T., Hori C., Kano K., Oka T. Purification and characterization of S-adenosyl-L-methionine decarboxylase from mouse mammary gland and liver. Biochemistry. 1979 Dec 11;18(25):5541–5548. doi: 10.1021/bi00592a003. [DOI] [PubMed] [Google Scholar]
  26. Seyfried C. E., Oleinik O. E., Degen J. L., Resing K., Morris D. R. Purification, properties and regulation of the level of bovine S-adenosylmethionine decarboxylase during lymphocyte mitogenesis. Biochim Biophys Acta. 1982 May 27;716(2):169–177. doi: 10.1016/0304-4165(82)90265-3. [DOI] [PubMed] [Google Scholar]
  27. Stevens L., McKinnon I. M., Turner R. M., North M. J. The effects of 1,4-diaminobutanone on polyamine metabolism in bacteria, a cellular slime mould and rat tissues [proceedings]. Biochem Soc Trans. 1978;6(2):407–409. doi: 10.1042/bst0060407. [DOI] [PubMed] [Google Scholar]
  28. Suresh M. R., Adiga P. R. Putrescine-sensitive (artifactual) and insensitive (biosynthetic) S-adenosyl-L-methionine decarboxylase activities of Lathyrus sativus seedlings. Eur J Biochem. 1977 Oct 3;79(2):511–518. doi: 10.1111/j.1432-1033.1977.tb11835.x. [DOI] [PubMed] [Google Scholar]
  29. Tabor C. W., Tabor H. 1,4-Diaminobutane (putrescine), spermidine, and spermine. Annu Rev Biochem. 1976;45:285–306. doi: 10.1146/annurev.bi.45.070176.001441. [DOI] [PubMed] [Google Scholar]
  30. Todhunter J. A. Reversible enzyme inhibition. Methods Enzymol. 1979;63:383–411. doi: 10.1016/0076-6879(79)63017-3. [DOI] [PubMed] [Google Scholar]
  31. Wickner R. B., Tabor C. W., Tabor H. Purification of adenosylmethionine decarboxylase from Escherichia coli W: evidence for covalently bound pyruvate. J Biol Chem. 1970 Apr 25;245(8):2132–2139. [PubMed] [Google Scholar]
  32. Williams-Ashman H. G., Schenone A. Methyl glyoxal bis(guanylhydrazone) as a potent inhibitor of mammalian and yeast S-adenosylmethionine decarboxylases. Biochem Biophys Res Commun. 1972 Jan 14;46(1):288–295. doi: 10.1016/0006-291x(72)90661-4. [DOI] [PubMed] [Google Scholar]
  33. Yamanoha B., Samejima K. Inhibition of S-adenosylmethionine decarboxylase from rat liver by synthetic decarboxylated S-adenosylmethionine and its analogs. Chem Pharm Bull (Tokyo) 1980 Jul;28(7):2232–2234. doi: 10.1248/cpb.28.2232. [DOI] [PubMed] [Google Scholar]
  34. Zappia V., Oliva A., Cacciapuoti G., Galletti P., Mignucci G., Cartení-Farina M. Substrate specificity of 5'-methylthioadenosine phosphorylase from human prostate. Biochem J. 1978 Dec 1;175(3):1043–1050. doi: 10.1042/bj1751043. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES