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Amino Acids

, Volume 34, Issue 2, pp 187–193 | Cite as

S-adenosylmethionine and its products

  • M. A. Grillo
  • S. Colombatto
Minireview Article

Summary.

S-adenosylmethionine is involved in many processes, mainly methylation, polyamine synthesis and radical-based catalysis. It is synthesised through the catalysis of differently regulated enzyme forms. When it is used, the compounds formed are reutilized in different ways: in case of methylation, its end product is homocysteine, which can be remethylated to methionine, give rise to cysteine in the so-called transsulphuration pathway, or be released; in the case of polyamine synthesis, the methylthioadenosine formed is cleaved and gives rise to compounds which can be reutilized; during radical-based catalysis, 5-deoxyadenosine is formed and this, too, is cleaved and reutilized.

Keywords: Homocysteine – Methylthioadenosine – 5-Deoxyadenosine 

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References

  1. Ansorena, E, Garcia-Trevijano, ER, Martinez-Chantar, ML, Huang, Z-Z, Chen, L, Mato, JM, Iraburo, M, Lu, SC, Avila, MA 2002S-adenosylmethionine and methylthioadenosine are antiapoptotic in cultured rat hepatocytes but proapoptotic in human hepatoma cellsHepatology35274280PubMedCrossRefGoogle Scholar
  2. Appleby, TC, Mathews, II, Porcelli, M, Cacciapuoti, G, Ealick, SE 2001Three-dimensional structure of a hyperthermophilic 5′-deoxy-5′-methylthioadenosine phosphorylase from Sulfolobus solfataricusJ Biol Chem2763923239242PubMedCrossRefGoogle Scholar
  3. Augoustides-Savvopoulou, P, Luka, Z, Karyda, S, Stabler, SP, Allen, RH, Patsiaoura, K, Wagner, C, Mudd, SH 2003Glycine N-methyltransferase deficiency: a new patient with a novel mutationJ Inherit Metab Dis26745759PubMedCrossRefGoogle Scholar
  4. Avila, MA, Berasain, C, Torres, L, Martin-Duce, A, Corrales, FJ, Yang, H, Prieto, J, Lu, SC, Cavalleria, J, Rodes, J, Mato, JM 2000Reduced mRNA abundance of the main enzymes involved in methionine metabolism in human liver cirrhosis and hepatocellular carcinomaJ Hepatol33907914PubMedCrossRefGoogle Scholar
  5. Banerjee, R, Evande, R, Kabil, O, Ojha, S, Taoka, S 2003Reaction mechanism and regulation of cystathionine beta-synthaseBiochim Biophys Acta16473035PubMedGoogle Scholar
  6. Banerjee, R, Zou, C 2005Redox regulation and reaction mechanism of human cystathionine-β-synthase: a PLP-dependent hemesensor proteinArch Biochem Biophys433144156PubMedCrossRefGoogle Scholar
  7. Bao, L, Vlcek, C, Paces, V, Kraus, JP 1998Identification and tissue distribution of human cystathionine β-synthase mRNA isoformsArch Biochem Biophys35095103PubMedCrossRefGoogle Scholar
  8. Barak, AJ, Beckenhauer, HC, Mailliard, ME, Kharbanda, KK, Tuma, DJ 2003Betaine lowers elevated S-adenosylhomocysteine levels in hepatocytes from ethanol-fed ratsJ Nutr13328452848PubMedGoogle Scholar
  9. Baric, I, Fumic, K, Glenn, B, Cuk, M, Schulze, A, Finkelstein, JD, James, SJ, Mejaski-Bosnjak, V, Pazanin, L, Pogribny, IP, Rados, M, Sarnavka, V, Scukanec-Spoljar, M, Allen, RH, Stabler, S, Uzelac, L, Vugrk, O, Wagner, C, Zeisel, S, Mudd, SH 2004S-adenosylhomo-cysteine hydrolase deficiency in a human: a genetic disorder of methionine metabolismProc Natl Acad Sci USA10142344239PubMedCrossRefGoogle Scholar
  10. Berasain, C, Hevia, H, Fernandez-Irigoyen, J, Larrea, E, Caballeria, J, Mato, JM, Prieto, J, Corrales, FJ, Garcia-Trevijiano, ER, Avila, MA 2004Methylthioadenosine phosphorylase gene expression is impaired in human liver cirrhosis and hepatocarcinoma 4Biochim Biophys Acta1690276284PubMedGoogle Scholar
  11. Breksa, AP,III, Garrow, TA 1999Recombinant human liver betaine-homocysteine S-methyltransferase: identification of three cysteine residues critical for zinc bindingBiochemistry381399113998PubMedCrossRefGoogle Scholar
  12. Cabrero, C, Puerta, J, Alemany, S 1987Purification and comparison of two forms of S-adenosyl-L-methionine synthetase from rat liverEur J Biochem170299304PubMedCrossRefGoogle Scholar
  13. Cacciapuoti, G, Moretti, MA, Forte, S, Brio, A, Camardella, L, Zappia, V, Porcelli, M 2004Methylthioadenosine phosphorylase from the archaeon Pyrococcus furiosus. Mechanism of the reaction and assignment of disulfide bondsEur J Biochem27148344844PubMedCrossRefGoogle Scholar
  14. Corrales, F, Ochoa, P, Rivas, C, Martin-Lomas, M, Mato, JM, Pajares, MA 1991Inhibition of glutathione synthesis in the liver leads to S-adenosyl-L-methionine synthetase reductionHepatology14528533PubMedGoogle Scholar
  15. Corrales, FJ, Ruiz, F, Mato, JM 1999In vivo regulation by glutathione of methionine adenosyltransferase S-nitrosylation in rat liverJ Hepatol31887894PubMedCrossRefGoogle Scholar
  16. Fabianowska-Majewska, K, Duley, J, Fairbanks, L, Simmonds, A, Wasiak, T 1994Substrate specificity of methylthioadenosine phosphorylase from human liverActa Biochim Pol41391395PubMedGoogle Scholar
  17. Fontecave, M, Ata, M, Mulliez, E 2004S-adenosylmethionine: nothing goes to wasteTrends Biochem Sci29243249PubMedCrossRefGoogle Scholar
  18. Forestier, M, Banninger, R, Reichen, J, Solioz, M 2003Betaine homocysteine methyltransferase: gene cloning and expression analysis in rat liver cirrhosisBiochim Biophys Acta16382934PubMedGoogle Scholar
  19. Fu, Z, Hu, Y, Konishi, K, Tarata, Y, Ogawa, H, Gomi, T, Fujioka, M, Takusagawa, F 1996Crystal structure of glicine N-methyltransferase from rat liverBiochemistry351198511993PubMedCrossRefGoogle Scholar
  20. Garcia-Trevijano, ER, Latasa, MU, Carretero, MV, Berasain, C, Mato, JM, Avila, MA 2000S-adenosylmethionine regulates MAT1A and MAT2A gene expression in cultured rat hepatocytes: a new role for S-adenosylmethionine in the maintenance of the differentiated status of the liverFASEB J1425112518PubMedCrossRefGoogle Scholar
  21. Ge, Y, Konrad, MA, Matherly, LH, Taub, JW 2001Transcriptional regulation of the human cystathionine β-synthase 1β basal promoter: synergistic transactivation by transcription factors NF-γ and Sp1/Sp3Biochem J35797105PubMedCrossRefGoogle Scholar
  22. Gonzalez, B, Pajares, MA, Hermoso, JA, Alvarez, L, Garrido, F, Sufrin, JR, Sanz-Aparicio, J 2000The crystal structure of tetrameric methionine adenosyltransferase from rat liver reveals the methionine-binding siteJ Mol Biol300363375PubMedCrossRefGoogle Scholar
  23. Gonzalez, B, Pajares, MA, Hermoso, JA, Guillerm, D, Guillerm, G, Sanz-Aparicio, J 2003Crystal structures of methionine adenosyltransferase complexed with substrates and products reveal the methionine-ATP recognition and give insights into the catalytic mechanismJ Mol Biol331407416PubMedCrossRefGoogle Scholar
  24. Grillo, MA, Colombatto, S 2007S-adenosylmethionine and radical-based catalysisAmino Acids32197202PubMedCrossRefGoogle Scholar
  25. Hibasami, H, Borchardt, , Chen, SY, Coward, JK, Pegg, AE 1980Studies of inhibition of rat spermidine synthase and spermine synthaseBiochem J187419428PubMedGoogle Scholar
  26. Hoffman, RM 1984Altered methionine metabolism, DNA methylation and oncogene expression in carcinogenesisBiochim Biophys Acta7384987PubMedGoogle Scholar
  27. Horikawa, S, Ishikawa, M, Ozasa, H, Tsukada, K 1989Isolation of a cDNA encoding the rat liver S-adenosylmethionine synthetaseEur J Biochem184497501PubMedCrossRefGoogle Scholar
  28. Hu, Y, Komoto, J, Huang, Y, Gomi, T, Ogawa, H, Takata, Y, Fujioka, M, Takusagawa, F 1999Crystal structure of S-adenosylhomocysteine hydrolase from rat liverBiochemistry3883238333PubMedCrossRefGoogle Scholar
  29. Huang, Y, Komoto, J, Konishi, K, Takata, Y, Ogawa, H, Gomi, T, Fujioka, M, Takusagawa, F 2000Mechanisms for auto-inhibition and forced product release in glycine N-methyltransferase: crystal structures of wild-type, mutant R175K and S-adenosylhomocysteine-bound R175K enzymesJ Mol Biol298149162PubMedCrossRefGoogle Scholar
  30. Ichikawa, A, Ohashi, Y, Terada, S, Natsuka, S, Ikura, K 2004In vitro modification of betaine-homocysteine S-methyltransferase by tissue-type transglutaminaseInt J Biochem Cell Biol3619811992PubMedCrossRefGoogle Scholar
  31. Jänne, J, Alhonen, L, Pietilä, M, Keinänen, A 2004Genetic approaches to the cellular functions of polyamines in mammalsEur J Biochem271877894PubMedCrossRefGoogle Scholar
  32. Kery, V, Ponelei, L, Kraus, JP 1998Trypsin cleavage of human cystathionine β-synthase into an evolutionarily conserved active core: structural and functional consequencesArch Biochem Biophys355222232PubMedCrossRefGoogle Scholar
  33. Kloor, D, Delabar, U, Mühlbauer, B, Luippold, G, Osswald, H 2002Tissue levels of S-adenosylhomocysteine in the rat kidney: effects of ischemia and homocysteineBiochem Pharmacol63809815PubMedCrossRefGoogle Scholar
  34. Kloor, D, Osswald, H 2004S-adenosylhomocysteine hydrolase as a target for intracellular adenosine actionTrends Pharmacol Sci25294297PubMedCrossRefGoogle Scholar
  35. Komoto, J, Yamada, T, Tarata, Y, Markham, GD, Takusagawa, F 2004Crystal structure of the S-adenosylmethionine synthetase ternary complex: a novel catalytic mechanism of S-adenosylmethionine synthesis from ATP and MetBiochemistry4318211831PubMedCrossRefGoogle Scholar
  36. Latasa, MU, Boukaba, A, Garcia-Trevijano, ER, Torres, L, Rodriguez, JL, Caballeria, J, Lu, SC, Lopez-Rodas, G, Franco, L, Mato, MJ, Avila, MA 2001Hepatocyte growth factor induces MAT2A expression and histone acetylation in rat hepatocytes: role in liver regenerationFASEB J1512481250PubMedGoogle Scholar
  37. Leal, NA, Olteanu, H, Banerjee, R, Bobik, TA 2004Human ATP:Cob(I)-alamin adenosyltransferase and its interaction with methionine synthase reductaseJ Biol Chem2794753647542PubMedCrossRefGoogle Scholar
  38. Leclerc, D, Wilson, A, Dumas, R, Gafuik, C, Song, D, Watkins, D, Heng, HHQ, Rommens, JM, Scherer, SW, Rosenblatt, DS, Gravel, RA 1998Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuriaProc Natl Acad Sci USA9530593064PubMedCrossRefGoogle Scholar
  39. Li M, Ou X, Lee TD, Zeng Y, Mato JM, Lu SC (2004) Silencing of human methionine adenosyltransferase 1A expression by methylation of the coding region. J Biol Chem (doi: 10.1074/jbc.M410405200)Google Scholar
  40. Luka, Z, Cerone, R, Philllips, JA,III, Mudd, SH, Wagner, C 2002Mutations in human glycine N-methyltransferase give insights into its role in methionine metabolismHum Genet1106874PubMedCrossRefGoogle Scholar
  41. Luka, Z, Wagner, C 2003Effect of naturally occurring mutations in human glycine N-methyltransferase on activity and conformationBiochem Biophys Res Commun31210671072PubMedCrossRefGoogle Scholar
  42. Martinez-Chantar, ML, Latasa, MU, Varela-Rey, M, Lu, SC, Garcia-Trevijano, ER, Mato, JM, Avila, MA 2003L-methionine availability regulates expression of the methionine adenosyltransferase 2A gene in human hepatocarcinoma cells. Role of S-adenosylmethionineJ Biol Chem2781988519890PubMedCrossRefGoogle Scholar
  43. Mato, JM, Alvarez, L, Ortiz, P, Pajares, MA 1997S-adenosylmethionine: molecular mechanisms and clinical implicationsPharmacol Ther73268280CrossRefGoogle Scholar
  44. Matthews, RG 2001Cobalamin-dependent methyltransferasesAcc Chem Res34681689PubMedCrossRefGoogle Scholar
  45. MccLain, CJ, Hill, DB, Song, Z, Chawla, R, Watson, WH, Chen, T, Barve, S 2002S-adenosylmethionine, cytokines, and alcoholic liver diseaseAlcohol27185192PubMedCrossRefGoogle Scholar
  46. Meier, M, Janosik, M, Kery, V, Kraus, JP, Burkhard, P 2001Structure of human cystathionine β-synthase: a unique pyridoxal 5′-phosphate-dependent heme proteinEMBO J2039103916PubMedCrossRefGoogle Scholar
  47. Meissner, T, Krause, E, Lödige, I, Vinkemeier, U 2004Arginine methylation of STAT1: a reassessmentCell118587590Google Scholar
  48. Mingorance, J, Alvarez, L, Sanchez-Gongora, E, Mato, JM, Pajares, MA 1996Site-directed mutagenesis of rat liver S-adenosylmethionine synthetase. Modification of a cysteine residue critical for the oligomeric stateBiochem J315761766PubMedGoogle Scholar
  49. Mowen, KA, Tang, J, Zhu, W, Schurter, BT, Shuai, K, Herschman, HR, David, M 2001Arginine methylation of STAT1 modulates IFNα/β-induced transcriptionCell104731741PubMedCrossRefGoogle Scholar
  50. Nieman, KM, Rowling, MJ, Garrow, TA, Schalinske, KL 2004Modulation of methyl group metabolism by streptozotocin-induced diabetes and all-trans-retinoic acidJ Biol Chem2794570845712PubMedCrossRefGoogle Scholar
  51. Noga, AA, Stead, LM, Zhao, Y, Brosnan, ME, Brosnan, JT, Vance, DE 2003Plasma homocysteine is regulated by phospholipids methylationJ Biol Chem27859525955PubMedCrossRefGoogle Scholar
  52. Ogawa, H, Gomi, T, Takusagawa, F, Fujioka, M 1998Structure, function and physiological role of glycine N-methyltransferaseInt J Biochem Cell Biol301326PubMedCrossRefGoogle Scholar
  53. Parker, NB, Yang, X, Hanke, J, Mason, KA, Schowen, RL, Borchardt, RT, Yin, DH 2003Trypanosoma cruzi. Molecular cloning and characterization of the adenosylhomocysteine hydrolaseExp Parasitol105149158PubMedCrossRefGoogle Scholar
  54. Pegg, AE 1986Recent advances in the biochemistry of polyamines in eukaryotesBiochem J234249262PubMedGoogle Scholar
  55. Porcelli, M, Moretti, MA, Concilio, L, Forte, S, Merlino, A, Graziano, G, Cacciapuoti, G 2005S-adenosylhomocysteine hydrolase from the archaeon Pyrococcus furiosus: biochemical characterization and analysis of protein structure by comparative molecular modelingProteins58815825PubMedCrossRefGoogle Scholar
  56. Reuber, BE, Karl, C, Reimann, SA, Mihalik, SJ, Dodt, G 1997Cloning and functional expression of a mammalian gene for a peroxisomal sarcosine oxidaseJ Biol Chem27267666776PubMedCrossRefGoogle Scholar
  57. Rowling, MJ, McMullen, MH, Chipman, DC, Schalinske, KL 2002Hepatic glycine N-methyltransferase nib up-regulated by excess dietary methionine in ratsJ Nutr13225452550PubMedGoogle Scholar
  58. Sanchez del Pino, MM, Corrales, FJ, Mato, JM 2000Hysteretic behavior of methionine adenosyltransferase III. Methionine switches between two conformations of the enzyme with different specific activityJ Biol Chem2752347623482CrossRefGoogle Scholar
  59. Sanchez del Pino, MM, Perez-Mato, I, Sanz, JM, Mato, JM, Corrales, FJ 2002Folding of dimeric methionine adenosyltransferase III. Identification of two folding intermediatesJ Biol Chem2771206112066PubMedCrossRefGoogle Scholar
  60. Stead, LM, Brosnan, ME, Brosnan, JT 2000Characterization of homocysteine metabolism in the rat liverBiochem J350685692PubMedCrossRefGoogle Scholar
  61. Subhi, AL, Diegelman, P, Porter, CW, Tang, B, Lu, ZJ, Markham, GD, Kruger, WD 2003Methylthioadenosine phosphorylase regulates ornithine decarboxylase by production of downstream metabolytesJ Biol Chem2784986849873PubMedCrossRefGoogle Scholar
  62. Szegedi, SS, Garrow, TA 2004Oligomerization is required for betaine-homocysteine S-methyltransferase functionArch Biochem Biophys4263242PubMedCrossRefGoogle Scholar
  63. Tanaka, N, Nakanishi, M, Kusakabe, Y, Shiraiwa, K, Yabe, S, Ito, Y, Kitade, Y, Nakamura, K 2004Crystal structure of S-adenosyl-L-homocysteine hydrolase from the human malaria parasite Plasmodium falciparumJ Mol Biol34310071017PubMedCrossRefGoogle Scholar
  64. Torres, L, Avila, MA, Carretero, MV, Latasa, MU, Caballeria, J, Lopez-Rodas, G, Boukaba, A, Lu, SC, Franco, L, Mato, JM 2000aLiver-specific methionine adenosyltransferase MAT1A gene expression is associated with a specific pattern of promoter methylation and histone acetylation: implications for MAT1A silencing during transformationFASEB J1495102Google Scholar
  65. Torres, L, Lopez-Rodas, G, Latasa, MU, Carretero, MV, Boukaba, A, Rodriguez, JL, Franco, L, Mato, JM, Avila, MA 2000bDNA methylation and histone acetylation of rat methionine adenosyltransferase 1A and 2A genes is tissue specificInt J Biochem Cell Biol32397404CrossRefGoogle Scholar
  66. Wagner, C, Decha-Umphai, W, Corbin, J 1989Phosphorylation modulates the activity of glycine N-methyltransferase, a folate binding protein. In vitro phosphorylation is inhibited by the natural folate ligandJ Biol Chem26496389642PubMedGoogle Scholar
  67. Wolthers, KR, Basran, J, Munro, AW, Scrutton, NS 2003Molecular dissection of human methionine synthase reductase: determination of the flavin redox potentials in full-length enzyme and isolated flavin-binding domainsBiochemistry4239113920PubMedCrossRefGoogle Scholar
  68. Yang, H, Sadda, MR, Li, M, Zeng, Y, Chen, L, Bae, W, Ou, X, Runnegar, MT, Mato, JM, Lu, SC 2004S-adenosylmethionine and its metabolite induce apoptosis in HepG2 cells: role of protein phasphatase 1 and Bcl-x5 Hepatology40221231PubMedCrossRefGoogle Scholar
  69. Yeo, E-J, Briggs, WT, Wagner, C 1999Inhibition of glycine N-methyltransferase by 5-methyltetrahydrofolate pentaglutamateJ Biol Chem2743755937564PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • M. A. Grillo
    • 1
  • S. Colombatto
    • 1
  1. 1.Dipartimento di Medicina e Oncologia Sperimentale, Sezione di BiochimicaUniversità di TorinoTorinoItaly

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