Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1979 Jun 15;180(3):515–522. doi: 10.1042/bj1800515

The decarboxylation of S-adenosylmethionine by detergent-treated extracts of rat liver

James Wilson 1, Arnaldo Corti 1,*, Margaret Hawkins 1, H Guy Williams-Ashman 1,†, Anthony E Pegg 2,†
PMCID: PMC1161089  PMID: 486130

Abstract

1. The production of 14CO2 from S-adenosyl[carboxyl-14C]methionine by rat liver extracts was investigated. It was found that, in addition to the well-known cytosolic putrescine-activated S-adenosylmethionine decarboxylase, an activity carrying out the production of 14CO2 could be extracted from a latent, particulate or membrane-bound form by treatment with buffer containing 1% (v/v) Triton X-100 [confirming the report of Sturman (1976) Biochim. Biophys. Acta 428, 56–69]. 2. The formation of 14CO2 by such detergent-solubilized extracts differed from that by cytosolic S-adenosylmethionine decarboxylase in a number of ways. The reaction by the solubilized extracts did not require putrescine and was not directly proportional to time of incubation or the amount of protein added. Instead, activity a showed a distinct lag period and was much greater when high concentrations of the extracts were used. The cytosolic S-adenosylmethionine decarboxylase was activated by putrescine, showed strict proportionality to protein added and the reaction proceeded at a constant rate. Cytosolic activity was not inhibited by homoserine or by S-adenosylhomocysteine, whereas the Triton-solubilized activity was strongly inhibited. 3. By using an acetone precipitate of Triton-treated homogenates as a source of the activity, it was found that decarboxylated S-adenosylmethionine was not present among the products of the reaction, although 5′-methylthioadenosine and 5-methylthioribose were found. Such extracts were able to produce 14CO2 when incubated with [U-14C]-homoserine, and 14CO2 production was greater when S-adenosyl[carboxyl-14C]methionine that had been degraded by heating at pH6 at 100°C for 30min (a procedure known to produce mainly 5′-methylthioadenosine and homoserine lactone) was used as a substrate than when S-adenosyl[carboxyl-14C]methionine was used. 4. These results indicate that the Triton-solubilized activity is not a real S-adenosylmethionine decarboxylase, but that 14CO2 is produced via a series of reactions involving degradation of the S-adenosyl-[carboxyl-14C]methionine. It is probable that this degradation can occur via several pathways. Our results would suggest that part of the reaction occurs via the production of S-adenosylhomocysteine, which can then be converted into 2-oxobutyrate via the transsulphuration pathway, and that part occurs via the production of homoserine by an enzyme converting S-adenosylmethionine into 5′-methylthioadenosine and homoserine lactone.

Full text

PDF
522

Selected References

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

  1. Edwards C. H., Wade W. D., Freeburne M. M., Jones E. G., Stacey R. E., Sherman L., Seo C. W., Edwards G. A. Formation of methionine from alpha-amino-n-butyric acid and 5'-methylthioadenosine in the rat. J Nutr. 1977 Oct;107(10):1927–1936. doi: 10.1093/jn/107.10.1927. [DOI] [PubMed] [Google Scholar]
  2. Eloranta T. O., Raina A. M. Formation of CO2 from the carboxyl group of S-adenosylmethionine by liver membrane-associated enzymes involves the demethylation-transsulphuration pathway. Biochem Biophys Res Commun. 1978 Sep 14;84(1):23–30. doi: 10.1016/0006-291x(78)90257-7. [DOI] [PubMed] [Google Scholar]
  3. Finkelstein J. D. Methionine metabolism in mammals: the biochemical basis for homocystinuria. Metabolism. 1974 Apr;23(4):387–398. doi: 10.1016/0026-0495(74)90057-2. [DOI] [PubMed] [Google Scholar]
  4. Fiume L., Campadelli-Fiume G., Magee P. N., Holsman J. Cellular injury and carcinogenesis. Inhibition of metabolism of dimethylnitrosamine by aminoacetonitrile. Biochem J. 1970 Dec;120(3):601–605. doi: 10.1042/bj1200601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Garbers D. L. Demonstration of 5'-methylthioadenosine phosphorylase activity in various rat tissues. Some properties of the enzyme from rat lung. Biochim Biophys Acta. 1978 Mar 14;523(1):82–93. doi: 10.1016/0005-2744(78)90011-6. [DOI] [PubMed] [Google Scholar]
  6. Janne J., Williams-Ashman H. G., Schenone A. Spermidine synthesizing enzymes in baker's yeast. Biochem Biophys Res Commun. 1971 Jun 18;43(6):1362–1368. doi: 10.1016/s0006-291x(71)80024-4. [DOI] [PubMed] [Google Scholar]
  7. Jänne J., Williams-Ashman H. G. On the purification of L-ornithine decarboxylase from rat prostate and effects of thiol compounds on the enzyme. J Biol Chem. 1971 Mar 25;246(6):1725–1732. [PubMed] [Google Scholar]
  8. MUDD S. H. Enzymatic cleavage of S-adenosylmethionine. J Biol Chem. 1959 Jan;234(1):87–92. [PubMed] [Google Scholar]
  9. Mudd S. H., Finkelstein J. D., Irreverre F., Laster L. Transsulfuration in mammals. Microassays and tissue distributions of three enzymes of the pathway. J Biol Chem. 1965 Nov;240(11):4382–4392. [PubMed] [Google Scholar]
  10. PARKS L. W., SCHLENK F. The stability and hydrolysis of S-adenosylmethionine; isolation of S-ribosylmethionine. J Biol Chem. 1958 Jan;230(1):295–305. [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. 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]
  14. 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]
  15. Pegg A. E., Williams-Ashman H. G. Phosphate-stimulated breakdown of 5'-methylthioadenosine by rat ventral prostate. Biochem J. 1969 Nov;115(2):241–247. doi: 10.1042/bj1150241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Raina A., Pajula R. L., Eloranta T. A rapid assay method for spermidine and spermine synthases. Distribution of polyamine-synthesizing enzymes and methionine adenosyltransferase in rat tissues. FEBS Lett. 1976 Sep 1;67(3):252–255. doi: 10.1016/0014-5793(76)80540-6. [DOI] [PubMed] [Google Scholar]
  17. SHAPIRO S. K., MATHER A. N. The enzymatic decomposition of S-adenosyl-L-methionine. J Biol Chem. 1958 Sep;233(3):631–633. [PubMed] [Google Scholar]
  18. Schmidt G. L., Cantoni G. L. Adenosylmethionine decarboxylase in developing rat brain. J Neurochem. 1973 May;20(5):1373–1385. doi: 10.1111/j.1471-4159.1973.tb00249.x. [DOI] [PubMed] [Google Scholar]
  19. Sturman J. A. Effect of methylglyoxal bis (guanylhydrazone) (MGBG) in vivo on the decarboxylation of s-adenosylmethionine and synthesis of spermidine in the rat and guinea pig. Life Sci. 1976 Apr 15;18(8):879–886. doi: 10.1016/0024-3205(76)90015-1. [DOI] [PubMed] [Google Scholar]
  20. Sturman J. A. Subcellular distribution of S-adenosylmethionine decarboxylase in rat liver. Evidence of decarboxylation of S-adenosylmethionine separate from synthesis of spermidine. Biochim Biophys Acta. 1976 Mar 25;428(1):56–69. doi: 10.1016/0304-4165(76)90108-2. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Swiatek K. R., Simon L. N., Chao K. L. Nicotinamide methyltransferase and S-adenosylmethionine: 5'-methylthioadenosine hydrolase. Control of transfer ribonucleic acid methylation. Biochemistry. 1973 Nov 6;12(23):4670–4674. doi: 10.1021/bi00747a019. [DOI] [PubMed] [Google Scholar]
  23. Symonds G. W., Brosnan M. E. Subcellular localization of putrescine-dependent S-adenosyl methionine decarboxylase in rat liver. FEBS Lett. 1977 Dec 15;84(2):385–387. doi: 10.1016/0014-5793(77)80730-8. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Toohey J. I. Methylthioadenosine nucleoside phosphorylase deficiency in methylthio-dependent cancer cells. Biochem Biophys Res Commun. 1978 Jul 14;83(1):27–35. doi: 10.1016/0006-291x(78)90393-5. [DOI] [PubMed] [Google Scholar]
  26. Williams-Ashman H. G., Corti A., Tadolini B. On the development of specific inhibitors of animal polyamine biosynthetic enzymes. Ital J Biochem. 1976 Jan-Feb;25(1):5–32. [PubMed] [Google Scholar]
  27. Williams-Ashman H. G., Jänne J., Coppoc G. L., Geroch M. E., Schenone A. New aspects of polyamine biosynthesis in eukaryotic organisms. Adv Enzyme Regul. 1972;10:225–245. doi: 10.1016/0065-2571(72)90016-7. [DOI] [PubMed] [Google Scholar]

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

RESOURCES