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Chemical Compound Review

AdoMet     (2S)-2-amino-4- [[(2R,3S,4R,5R)-5-(6...

Synonyms: Donamet, Ademetionine, SAMe, SAM-e, Sam-Sulfate, ...
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Disease relevance of S-adenosylmethionine


High impact information on S-adenosylmethionine

  • In an in vivo model of lethal hepatitis by TNF-alpha, depletion of SAM preceded activation of caspases 8 and 3, massive liver damage, and death of the mice [1].
  • In contrast, minimal hepatic SAM depletion, caspase activation, and liver damage were seen in ASMase-/- mice [1].
  • This abnormally low rate is due not to a decreased flux through the primarily defective enzyme, MAT, since SAM is produced at an essentially normal rate of 18 mmol/d, but rather to a rate of homocysteine methylation which is abnormally high in the face of the very elevated methionine concentrations demonstrated in this patient [5].
  • Crystal structure of coproporphyrinogen III oxidase reveals cofactor geometry of Radical SAM enzymes [6].
  • SAM level and SAM:S-adenosylhomocysteine (SAH) ratio increased by 50-75% after MAT1A transfection and by an additional 60-80% after MAT2A antisense treatment [7].

Chemical compound and disease context of S-adenosylmethionine


Biological context of S-adenosylmethionine

  • DNA methylation changed in parallel to changes in SAM level and SAM:SAH ratio [7].
  • When LTL are cultured under conditions of high cell density, there is an initial phase of rapid protein synthesis and accumulation of SAM as found under normal culture conditions, but this soon ceases [9].
  • Mutations of the conserved Arg253 uniquely affect the SAM kinetics, thus establishing this position as part of the SAM binding site [10].
  • Recent evidence indicates that not only is SAM the main biological methyl group donor and an intermediate metabolite in methionine catabolism, but it is also an intracellular control switch that regulates essential hepatic functions such as liver regeneration and differentiation as well as the sensitivity of this organ to injury [11].
  • In this study, we found that high levels of methionine inhibited the biosynthesis of S-adenosylmethionine (SAM) and that reduced intracellular levels of SAM are correlated with defective chemotactic movements and reduced developmental gene expression [12].

Anatomical context of S-adenosylmethionine


Associations of S-adenosylmethionine with other chemical compounds


Gene context of S-adenosylmethionine

  • A major mechanism for the increase in SAM level is increased MAT2A transcription [13].
  • If SAM levels also decrease in these cells, this may contribute to the induction of tumor necrosis factor (TNF) expression and release [8].
  • CSF MBP mirrored SAM concentration and there was a significant inverse relationship between the two [2].
  • MTF, SAM, and MBP returned to normal values by the end of treatment, while MET was increased significantly [2].
  • Despite lacking sequence similarity to any protein of known three-dimensional structure, the tertiary structure of bacterial TPMT reveals a classical SAM-dependent methyltransferase topology, consisting of a seven-stranded beta-sheet flanked by alpha-helices on both sides [22].

Analytical, diagnostic and therapeutic context of S-adenosylmethionine

  • The ratios of SAM to SAH were 1.8, 2.7 and 1.5 in the deficient group for weeks 2, 3 and 4 of the experiment, and the values were 9.7, 7.1 and 8.9 for the pair-fed control group and 10.3, 8.8 and 8.0 for the control group ad libitum fed [23].
  • Double-blind, placebo-controlled pharmacodynamic studies with a nutraceutical and a pharmaceutical dose of ademetionine (SAMe) in elderly subjects, utilizing EEG mapping and psychometry [24].
  • Northern blot experiments demonstrated that the Lactococcus lactis MG1363 cfa gene is mainly expressed as a bicistronic transcript together with metK, the gene encoding SAM synthetase, and is highly induced by acidity [25].


  1. Acidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor-induced lethal hepatitis. Marí, M., Colell, A., Morales, A., Pañeda, C., Varela-Nieto, I., García-Ruiz, C., Fernández-Checa, J.C. J. Clin. Invest. (2004) [Pubmed]
  2. Demyelination and single-carbon transfer pathway metabolites during the treatment of acute lymphoblastic leukemia: CSF studies. Surtees, R., Clelland, J., Hann, I. J. Clin. Oncol. (1998) [Pubmed]
  3. A new medical approach to the treatment of osteoarthritis. Report of an open phase IV study with ademetionine (Gumbaral). Berger, R., Nowak, H. Am. J. Med. (1987) [Pubmed]
  4. Rickettsial metK-encoded methionine adenosyltransferase expression in an Escherichia coli metK deletion strain. Driskell, L.O., Tucker, A.M., Winkler, H.H., Wood, D.O. J. Bacteriol. (2005) [Pubmed]
  5. Transsulfuration in an adult with hepatic methionine adenosyltransferase deficiency. Gahl, W.A., Bernardini, I., Finkelstein, J.D., Tangerman, A., Martin, J.J., Blom, H.J., Mullen, K.D., Mudd, S.H. J. Clin. Invest. (1988) [Pubmed]
  6. Crystal structure of coproporphyrinogen III oxidase reveals cofactor geometry of Radical SAM enzymes. Layer, G., Moser, J., Heinz, D.W., Jahn, D., Schubert, W.D. EMBO J. (2003) [Pubmed]
  7. Differential expression of methionine adenosyltransferase genes influences the rate of growth of human hepatocellular carcinoma cells. Cai, J., Mao, Z., Hwang, J.J., Lu, S.C. Cancer Res. (1998) [Pubmed]
  8. Role of abnormal methionine metabolism in alcoholic liver injury. Lu, S.C., Tsukamoto, H., Mato, J.M. Alcohol (2002) [Pubmed]
  9. Methionine utilization in long-term human lymphoid cell lines. Guarini, L., Sturman, J.A., Gaull, G.E., Beratis, N.G. J. Cell. Physiol. (1981) [Pubmed]
  10. Conserved and nonconserved residues in the substrate binding site of 7,8-diaminopelargonic acid synthase from Escherichia coli are essential for catalysis. Sandmark, J., Eliot, A.C., Famm, K., Schneider, G., Kirsch, J.F. Biochemistry (2004) [Pubmed]
  11. Regulation of mammalian liver methionine adenosyltransferase. Corrales, F.J., Pérez-Mato, I., Sánchez Del Pino, M.M., Ruiz, F., Castro, C., García-Trevijano, E.R., Latasa, U., Martínez-Chantar, M.L., Martínez-Cruz, A., Avila, M.A., Mato, J.M. J. Nutr. (2002) [Pubmed]
  12. Methionine inhibits developmental aggregation of Myxococcus xanthus by blocking the biosynthesis of S-adenosyl methionine. Shi, W., Zusman, D.R. J. Bacteriol. (1995) [Pubmed]
  13. The role of c-Myb in the up-regulation of methionine adenosyltransferase 2A expression in activated Jurkat cells. Zeng, Z., Yang, H., Huang, Z.Z., Chen, C., Wang, J., Lu, S.C. Biochem. J. (2001) [Pubmed]
  14. Studies of methionine cycle intermediates (SAM, SAH), DNA methylation and the impact of folate deficiency on tumor numbers in Min mice. Sibani, S., Melnyk, S., Pogribny, I.P., Wang, W., Hiou-Tim, F., Deng, L., Trasler, J., James, S.J., Rozen, R. Carcinogenesis (2002) [Pubmed]
  15. Conversion of spironolactone to 7 alpha-thiomethylspironolactone by hepatic and renal microsomes. LaCagnin, L.B., Lutsie, P., Colby, H.D. Biochem. Pharmacol. (1987) [Pubmed]
  16. Methionine transport in Yersinia pestis. Montie, D.B., Montie, T.C. J. Bacteriol. (1975) [Pubmed]
  17. Phosphatidylethanolamine N-methyltransferase activity in isolated rod outer segments from bovine retina. Roque, M.E., Giusto, N.M. Exp. Eye Res. (1995) [Pubmed]
  18. Oxygen-independent coproporphyrinogen-III oxidase HemN from Escherichia coli. Layer, G., Verfürth, K., Mahlitz, E., Jahn, D. J. Biol. Chem. (2002) [Pubmed]
  19. The clinical potential of ademetionine (S-adenosylmethionine) in neurological disorders. Bottiglieri, T., Hyland, K., Reynolds, E.H. Drugs (1994) [Pubmed]
  20. Cork taint of wines: role of the filamentous fungi isolated from cork in the formation of 2,4,6-trichloroanisole by o methylation of 2,4,6-trichlorophenol. Alvarez-Rodríguez, M.L., López-Ocaña, L., López-Coronado, J.M., Rodríguez, E., Martínez, M.J., Larriba, G., Coque, J.J. Appl. Environ. Microbiol. (2002) [Pubmed]
  21. A glycine N-methyltransferase knockout mouse model for humans with deficiency of this enzyme. Luka, Z., Capdevila, A., Mato, J.M., Wagner, C. Transgenic Res. (2006) [Pubmed]
  22. Tertiary structure of thiopurine methyltransferase from Pseudomonas syringae, a bacterial orthologue of a polymorphic, drug-metabolizing enzyme. Scheuermann, T.H., Lolis, E., Hodsdon, M.E. J. Mol. Biol. (2003) [Pubmed]
  23. Hepatic one-carbon metabolism in early folate deficiency in rats. Balaghi, M., Horne, D.W., Wagner, C. Biochem. J. (1993) [Pubmed]
  24. Double-blind, placebo-controlled pharmacodynamic studies with a nutraceutical and a pharmaceutical dose of ademetionine (SAMe) in elderly subjects, utilizing EEG mapping and psychometry. Arnold, O., Saletu, B., Anderer, P., Assandri, A., di Padova, C., Corrado, M., Saletu-Zyhlarz, G.M. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. (2005) [Pubmed]
  25. Transcriptional analysis of the cyclopropane fatty acid synthase gene of Lactococcus lactis MG1363 at low pH. Budin-Verneuil, A., Maguin, E., Auffray, Y., Ehrlich, S.D., Pichereau, V. FEMS Microbiol. Lett. (2005) [Pubmed]
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