S-Adenosylmethionine (T3D4456)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesGene RegulationTargets (10)XML
Targets (10)
Record Information
Version2.0
Creation Date2014-08-29 06:51:25 UTC
Update Date2014-12-24 20:26:50 UTC
Accession NumberT3D4456
Identification
Common NameS-Adenosylmethionine
ClassSmall Molecule
DescriptionPhysiologic methyl radical donor involved in enzymatic transmethylation reactions and present in all living organisms. It possesses anti-inflammatory activity and has been used in treatment of chronic liver disease. (From Merck, 11th ed). S-Adenosylmethionine is only found in individuals that have used or taken this drug. It is a physiologic methyl radical donor involved in enzymatic transmethylation reactions and present in all living organisms. It possesses anti-inflammatory activity and has been used in treatment of chronic liver disease. (From Merck, 11th ed)S-Adenosylmethionine (SAMe) is a natural substance present in the cells of the body. It is a direct metabolite of the essential amino acid L-methionine. SAMe plays a crucial biochemical role in the body by donating a one-carbon methyl group in a process called transmethylation. SAMe, formed from the reaction of L-methionine and adenosine triphosphate catalyzed by the enzyme S-adenosylmethionine synthetase, is the methyl-group donor in the biosynthesis of both DNA and RNA nucleic acids, phospholipids, proteins, epinephrine, melatonin, creatine and other molecules.
Compound Type
  • Amine
  • Animal Toxin
  • Dietary Supplement
  • Drug
  • Ether
  • Food Toxin
  • Metabolite
  • Micronutrient
  • Natural Compound
  • Nutraceutical
  • Organic Compound
  • Supplement
Chemical Structure
Thumb
MOLSDF3D-SDFPDBSMILESInChI View 3D Structure
Synonyms
Synonym
(3S)-5'-[(3-amino-3-carboxypropyl)methylsulfonio]-5'-deoxyadenosine
(3S)-5'-[(3-amino-3-Carboxypropyl)methylsulfonio]-5'-deoxyadenosine, inner salt
2-S-Adenosyl-L-methionine
5'-Deoxyadenosine-5'-L-methionine disulfate ditosylate
5'-Deoxyadenosine-5'-L-methionine disulphate ditosylate
Active methionine
Acylcarnitine
Ademetionine
Adenosylmethionine
AdoMet
Donamet
L-S-Adenosylmethionine
S-(5'-Adenosyl)-L-methionine
S-(5'-Deoxyadenosin-5'-yl)-L-methionine
S-Adenosyl methionine
S-Adenosyl-L-methionine
S-Adenosyl-L-Methionine Disulfate Tosylate
S-Adenosyl-L-Methionine Disulphate Tosylate
S-Adenosyl-methionine
SAM
Sam-Sulfate
SAMe
SAMe Rx-Mood
[1-(Adenin-9-yl)-1,5-dideoxy-beta-D-ribofuranos-5-yl][(3S)-3-amino-3-carboxypropyl](methyl)sulfonium
Chemical FormulaC15H23N6O5S
Average Molecular Mass399.445 g/mol
Monoisotopic Mass399.145 g/mol
CAS Registry Number29908-03-0
IUPAC Name[(3S)-3-amino-3-carboxypropyl]({[(2S,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl})methylsulfanium
Traditional NameSAMe
SMILES[H][C@](N)(CC[S+](C)C[C@@]1([H])O[C@@]([H])(N2C=NC3=C(N)N=CN=C23)[C@]([H])(O)[C@]1([H])O)C(O)=O
InChI IdentifierInChI=1S/C15H22N6O5S/c1-27(3-2-7(16)15(24)25)4-8-10(22)11(23)14(26-8)21-6-20-9-12(17)18-5-19-13(9)21/h5-8,10-11,14,22-23H,2-4,16H2,1H3,(H2-,17,18,19,24,25)/p+1/t7-,8+,10+,11+,14+,27?/m0/s1
InChI KeyInChIKey=MEFKEPWMEQBLKI-AIRLBKTGSA-O
Chemical Taxonomy
Description belongs to the class of organic compounds known as 5'-deoxy-5'-thionucleosides. These are 5'-deoxyribonucleosides in which the ribose is thio-substituted at the 5'position by a S-alkyl group.
KingdomOrganic compounds
Super ClassNucleosides, nucleotides, and analogues
Class5'-deoxyribonucleosides
Sub Class5'-deoxy-5'-thionucleosides
Direct Parent5'-deoxy-5'-thionucleosides
Alternative Parents
Substituents
  • 5'-deoxy-5'-thionucleoside
  • Methionine or derivatives
  • N-glycosyl compound
  • Glycosyl compound
  • Pentose monosaccharide
  • 6-aminopurine
  • Alpha-amino acid
  • L-alpha-amino acid
  • Alpha-amino acid or derivatives
  • Imidazopyrimidine
  • Purine
  • Aminopyrimidine
  • Hydroxy fatty acid
  • Thia fatty acid
  • N-substituted imidazole
  • Fatty acyl
  • Monosaccharide
  • Imidolactam
  • Pyrimidine
  • Azole
  • Imidazole
  • Heteroaromatic compound
  • Tetrahydrofuran
  • Amino acid or derivatives
  • 1,2-diol
  • Amino acid
  • Secondary alcohol
  • Oxacycle
  • Azacycle
  • Carboxylic acid derivative
  • Carboxylic acid
  • Organoheterocyclic compound
  • Monocarboxylic acid or derivatives
  • Organic oxide
  • Organopnictogen compound
  • Alcohol
  • Carbonyl group
  • Organic oxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Primary amine
  • Organosulfur compound
  • Organooxygen compound
  • Primary aliphatic amine
  • Amine
  • Organonitrogen compound
  • Organic cation
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginEndogenous
Cellular Locations
  • Endoplasmic reticulum
  • Membrane
  • Mitochondria
  • Nucleus
Biofluid LocationsNot Available
Tissue Locations
  • Epidermis
  • Eye Lens
  • Fibroblasts
  • Gonads
  • Intestine
  • Kidney
  • Muscle
  • Myelin
  • Placenta
  • Prostate
  • Skeletal Muscle
  • Testes
Pathways
NameSMPDB LinkKEGG Link
Betaine MetabolismSMP00123 map00260
Carnitine SynthesisSMP00465 Not Available
Catecholamine BiosynthesisSMP00012 map00350
Glycine and Serine MetabolismSMP00004 map00260
Methionine MetabolismSMP00033 map00270
Spermidine and Spermine BiosynthesisSMP00445 Not Available
S-Adenosylhomocysteine (SAH) Hydrolase DeficiencySMP00214 Not Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling Point78 °C
Solubility1.19e+00 g/l
LogP-5.3
Predicted Properties
PropertyValueSource
Water Solubility1.19 g/LALOGPS
logP-2ALOGPS
logP-5.3ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)1.7ChemAxon
pKa (Strongest Basic)9.41ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count10ChemAxon
Hydrogen Donor Count5ChemAxon
Polar Surface Area182.63 ŲChemAxon
Rotatable Bond Count7ChemAxon
Refractivity96.23 m³·mol⁻¹ChemAxon
Polarizability40.37 ųChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0a5c-5965000000-324e4a3cbf936132bcf12017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (3 TMS) - 70eV, Positivesplash10-00ea-7958582000-3dd40cf273f182ee53dd2017-10-06View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0002-0019000000-6dfa0dc65a9863755c2a2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0udj-0293000000-57cc9d4430592060d41d2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-0udr-1940000000-ed4985bea80649d27efe2017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-000b-8920000000-8f05e9898f0d26ddf3f82017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QQ , positivesplash10-000e-9400000000-e5c5617045d9915e8e462017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-IT , positivesplash10-0udi-0090000000-93017671648813ece8a52017-09-14View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0914000000-95030ceaf1c187dcf6562017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0900000000-c3fae8b7a68475b614a42017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-2900000000-44078fd7eaeafcc5bba82017-09-01View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-1927000000-02f9d1735282c46e73182021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-1900000000-aa88bbdd6c68c8e333632021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-0bti-7900000000-003aba988a5c7e2f65342021-09-24View Spectrum
1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)Not Available2021-09-29View Spectrum
Toxicity Profile
Route of ExposureS-Adenosylmethionine is absorbed from the small intestine following oral intake. As absorption is affected by food, it is best to take on an empty stomach. Bioavailability is low following oral intake.
Mechanism of ToxicityS-Adenosylmethionine (SAMe) is a natural substance present in the cells of the body. It is a direct metabolite of the essential amino acid L-methionine. SAMe plays a crucial biochemical role in the body by donating a one-carbon methyl group in a process called transmethylation. SAMe, formed from the reaction of L-methionine and adenosine triphosphate catalyzed by the enzyme S-adenosylmethionine synthetase, is the methyl-group donor in the biosynthesis of both DNA and RNA nucleic acids, phospholipids, proteins, epinephrine, melatonin, creatine and other molecules.
MetabolismSignificant first-pass metabolism in the liver. Approximately 50% of S-Adenosylmethionine (SAMe) is metabolized in the liver. SAMe is metabolized to S-adenosylhomocysteine, which is then metabolized to homocysteine. Homocysteine can either be metabolized to cystathionine and then cysteine or to methionine. The cofactor in the metabolism of homocysteine to cysteine is vitamin B6. Cofactors for the metabolism of homocysteine to methionine are folic acid, vitamin B12 and betaine.
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesS-Adenosylmethionine (SAMe) is used as a drug in Europe for the treatment of depression, liver disorders, fibromyalgia, and osteoarthritis. It has also been introduced into the United States market as a dietary supplement for the support of bone and joint health, as well as mood and emotional well being.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00118
HMDB IDHMDB01185
PubChem Compound ID34756
ChEMBL IDCHEMBL224120
ChemSpider ID31983
KEGG IDC00019
UniProt IDNot Available
OMIM ID
ChEBI ID15414
BioCyc IDS-ADENOSYLMETHIONINE
CTD IDNot Available
Stitch IDNot Available
PDB IDSAM
ACToR IDNot Available
Wikipedia LinkS-Adenosylmethionine
References
Synthesis Reference

Takayasu Tsuchida, Fumihiro Yoshinaga, Shinji Okumura, “Method for producing S-adenosylmethionine or methylthioadenosine by yeast.” U.S. Patent US3962034, issued November, 1971.

MSDSLink
General References
  1. Finkelstein JD, Martin JJ: Homocysteine. Int J Biochem Cell Biol. 2000 Apr;32(4):385-9. [10762063 ]
  2. Fodinger M, Horl WH, Sunder-Plassmann G: Molecular biology of 5,10-methylenetetrahydrofolate reductase. J Nephrol. 2000 Jan-Feb;13(1):20-33. [10720211 ]
  3. Roje S: S-Adenosyl-L-methionine: beyond the universal methyl group donor. Phytochemistry. 2006 Aug;67(15):1686-98. [16766004 ]
  4. Loenen WA: S-adenosylmethionine: jack of all trades and master of everything? Biochem Soc Trans. 2006 Apr;34(Pt 2):330-3. [16545107 ]
  5. Chiang PK, Gordon RK, Tal J, Zeng GC, Doctor BP, Pardhasaradhi K, McCann PP: S-Adenosylmethionine and methylation. FASEB J. 1996 Mar;10(4):471-80. [8647346 ]
  6. Chamberlin ME, Ubagai T, Mudd SH, Wilson WG, Leonard JV, Chou JY: Demyelination of the brain is associated with methionine adenosyltransferase I/III deficiency. J Clin Invest. 1996 Aug 15;98(4):1021-7. [8770875 ]
  7. Koeberl DD, Young SP, Gregersen NS, Vockley J, Smith WE, Benjamin DK Jr, An Y, Weavil SD, Chaing SH, Bali D, McDonald MT, Kishnani PS, Chen YT, Millington DS: Rare disorders of metabolism with elevated butyryl- and isobutyryl-carnitine detected by tandem mass spectrometry newborn screening. Pediatr Res. 2003 Aug;54(2):219-23. Epub 2003 May 7. [12736383 ]
  8. Scalabrino G, Pigatto P, Ferioli ME, Modena D, Puerari M, Caru A: Levels of activity of the polyamine biosynthetic decarboxylases as indicators of degree of malignancy of human cutaneous epitheliomas. J Invest Dermatol. 1980 Mar;74(3):122-4. [7359002 ]
  9. Struys EA, Jansen EE, de Meer K, Jakobs C: Determination of S-adenosylmethionine and S-adenosylhomocysteine in plasma and cerebrospinal fluid by stable-isotope dilution tandem mass spectrometry. Clin Chem. 2000 Oct;46(10):1650-6. [11017945 ]
  10. Kaneoka H, Uesugi N, Moriguchi A, Hirose S, Takayanagi M, Yamaguchi S, Shigematsu Y, Yasuno T, Sasatomi Y, Saito T: Carnitine palmitoyltransferase II deficiency due to a novel gene variant in a patient with rhabdomyolysis and ARF. Am J Kidney Dis. 2005 Mar;45(3):596-602. [15754283 ]
  11. Rosen RT, Hiserodt RD, Fukuda EK, Ruiz RJ, Zhou Z, Lech J, Rosen SL, Hartman TG: The determination of metabolites of garlic preparations in breath and human plasma. Biofactors. 2000;13(1-4):241-9. [11237188 ]
  12. McFadden PN, Horwitz J, Clarke S: Protein carboxyl methyltransferase from cow eye lens. Biochem Biophys Res Commun. 1983 Jun 15;113(2):418-24. [6870865 ]
  13. Garibotto G, Sofia A, Valli A, Tarroni A, Di Martino M, Cappelli V, Aloisi F, Procopio V: Causes of hyperhomocysteinemia in patients with chronic kidney diseases. Semin Nephrol. 2006 Jan;26(1):3-7. [16412817 ]
  14. Spiekerkoetter U, Tokunaga C, Wendel U, Mayatepek E, Ijlst L, Vaz FM, van Vlies N, Overmars H, Duran M, Wijburg FA, Wanders RJ, Strauss AW: Tissue carnitine homeostasis in very-long-chain acyl-CoA dehydrogenase-deficient mice. Pediatr Res. 2005 Jun;57(6):760-4. Epub 2005 Mar 17. [15774826 ]
  15. Jones MG, Goodwin CS, Amjad S, Chalmers RA: Plasma and urinary carnitine and acylcarnitines in chronic fatigue syndrome. Clin Chim Acta. 2005 Oct;360(1-2):173-7. [15967423 ]
  16. Kelm A, Shaw L, Schauer R, Reuter G: The biosynthesis of 8-O-methylated sialic acids in the starfish Asterias rubens--isolation and characterisation of S-adenosyl-L-methionine:sialate-8-O-methyltransferase. Eur J Biochem. 1998 Feb 1;251(3):874-84. [9490063 ]
  17. Solano AR, Sanchez ML, Podesta EJ, Turyn D, Dellacha JM: Membrane methylation in isolated rat testis interstitial cells unmasks functional luteinizing hormone receptors. Biochim Biophys Acta. 1987 Apr 2;928(1):107-13. [3828399 ]
  18. D'Erme M, Santoro R, Allegra P, Reale A, Marenzi S, Strom R, Caiafa P: Inhibition of CpG methylation in linker DNA by H1 histone. Biochim Biophys Acta. 1993 May 28;1173(2):209-16. [8504169 ]
  19. Hoppel CL, Genuth SM: Urinary excretion of acetylcarnitine during human diabetic and fasting ketosis. Am J Physiol. 1982 Aug;243(2):E168-72. [6810706 ]
  20. Scott JM, Weir DG: The methyl folate trap. A physiological response in man to prevent methyl group deficiency in kwashiorkor (methionine deficiency) and an explanation for folic-acid induced exacerbation of subacute combined degeneration in pernicious anaemia. Lancet. 1981 Aug 15;2(8242):337-40. [6115113 ]
  21. Sreekumar A, Poisson LM, Rajendiran TM, Khan AP, Cao Q, Yu J, Laxman B, Mehra R, Lonigro RJ, Li Y, Nyati MK, Ahsan A, Kalyana-Sundaram S, Han B, Cao X, Byun J, Omenn GS, Ghosh D, Pennathur S, Alexander DC, Berger A, Shuster JR, Wei JT, Varambally S, Beecher C, Chinnaiyan AM: Metabolomic profiles delineate potential role for sarcosine in prostate cancer progression. Nature. 2009 Feb 12;457(7231):910-4. doi: 10.1038/nature07762. [19212411 ]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

Target Details
1. Glycine N-methyltransferase
General Function:
Glycine n-methyltransferase activity
Specific Function:
Catalyzes the methylation of glycine by using S-adenosylmethionine (AdoMet) to form N-methylglycine (sarcosine) with the concomitant production of S-adenosylhomocysteine (AdoHcy). Possible crucial role in the regulation of tissue concentration of AdoMet and of metabolism of methionine.
Gene Name:
GNMT
Uniprot ID:
Q14749
Molecular Weight:
32742.0 Da
References
  1. Rowling MJ, Schalinske KL: Retinoid compounds activate and induce hepatic glycine N-methyltransferase in rats. J Nutr. 2001 Jul;131(7):1914-7. [11435507 ]
  2. Luka Z, Cerone R, Phillips JA 3rd, Mudd HS, Wagner C: Mutations in human glycine N-methyltransferase give insights into its role in methionine metabolism. Hum Genet. 2002 Jan;110(1):68-74. Epub 2001 Dec 7. [11810299 ]
  3. Rowling MJ, McMullen MH, Chipman DC, Schalinske KL: Hepatic glycine N-methyltransferase is up-regulated by excess dietary methionine in rats. J Nutr. 2002 Sep;132(9):2545-50. [12221207 ]
  4. Moller MT, Samari HR, Fengsrud M, Stromhaug PE, oStvold AC, Seglen PO: Okadaic acid-induced, naringin-sensitive phosphorylation of glycine N-methyltransferase in isolated rat hepatocytes. Biochem J. 2003 Jul 15;373(Pt 2):505-13. [12697024 ]
  5. Uthus EO, Brown-Borg HM: Altered methionine metabolism in long living Ames dwarf mice. Exp Gerontol. 2003 May;38(5):491-8. [12742526 ]
Target Details
2. S-adenosylmethionine synthase isoform type-1
General Function:
Methionine adenosyltransferase activity
Specific Function:
Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
Gene Name:
MAT1A
Uniprot ID:
Q00266
Molecular Weight:
43647.6 Da
References
  1. Carretero MV, Latasa MU, Garcia-Trevijano ER, Corrales FJ, Wagner C, Mato JM, Avila MA: Inhibition of liver methionine adenosyltransferase gene expression by 3-methylcolanthrene: protective effect of S-adenosylmethionine. Biochem Pharmacol. 2001 May 1;61(9):1119-28. [11301045 ]
  2. Martinez-Chantar ML, Corrales FJ, Martinez-Cruz LA, Garcia-Trevijano ER, Huang ZZ, Chen L, Kanel G, Avila MA, Mato JM, Lu SC: Spontaneous oxidative stress and liver tumors in mice lacking methionine adenosyltransferase 1A. FASEB J. 2002 Aug;16(10):1292-4. Epub 2002 Jun 7. [12060674 ]
  3. Santamaria E, Avila MA, Latasa MU, Rubio A, Martin-Duce A, Lu SC, Mato JM, Corrales FJ: Functional proteomics of nonalcoholic steatohepatitis: mitochondrial proteins as targets of S-adenosylmethionine. Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3065-70. Epub 2003 Mar 11. [12631701 ]
  4. Martinez-Chantar ML, Latasa MU, Varela-Rey M, Lu SC, Garcia-Trevijano ER, Mato JM, Avila MA: L-methionine availability regulates expression of the methionine adenosyltransferase 2A gene in human hepatocarcinoma cells: role of S-adenosylmethionine. J Biol Chem. 2003 May 30;278(22):19885-90. Epub 2003 Mar 26. [12660248 ]
  5. Martinez-Chantar ML, Garcia-Trevijano ER, Latasa MU, Martin-Duce A, Fortes P, Caballeria J, Avila MA, Mato JM: Methionine adenosyltransferase II beta subunit gene expression provides a proliferative advantage in human hepatoma. Gastroenterology. 2003 Apr;124(4):940-8. [12671891 ]
Target Details
3. Cystathionine beta-synthase
General Function:
Ubiquitin protein ligase binding
Specific Function:
Hydro-lyase catalyzing the first step of the transsulfuration pathway, where the hydroxyl group of L-serine is displaced by L-homocysteine in a beta-replacement reaction to form L-cystathionine, the precursor of L-cysteine. This catabolic route allows the elimination of L-methionine and the toxic metabolite L-homocysteine (PubMed:23981774, PubMed:20506325, PubMed:23974653). Also involved in the production of hydrogen sulfide, a gasotransmitter with signaling and cytoprotective effects on neurons (By similarity).
Gene Name:
CBS
Uniprot ID:
P35520
Molecular Weight:
60586.05 Da
References
  1. Janosik M, Kery V, Gaustadnes M, Maclean KN, Kraus JP: Regulation of human cystathionine beta-synthase by S-adenosyl-L-methionine: evidence for two catalytically active conformations involving an autoinhibitory domain in the C-terminal region. Biochemistry. 2001 Sep 4;40(35):10625-33. [11524006 ]
  2. Jacobs RL, Stead LM, Brosnan ME, Brosnan JT: Hyperglucagonemia in rats results in decreased plasma homocysteine and increased flux through the transsulfuration pathway in liver. J Biol Chem. 2001 Nov 23;276(47):43740-7. Epub 2001 Sep 14. [11559709 ]
  3. Choumenkovitch SF, Selhub J, Bagley PJ, Maeda N, Nadeau MR, Smith DE, Choi SW: In the cystathionine beta-synthase knockout mouse, elevations in total plasma homocysteine increase tissue S-adenosylhomocysteine, but responses of S-adenosylmethionine and DNA methylation are tissue specific. J Nutr. 2002 Aug;132(8):2157-60. [12163655 ]
  4. Evande R, Blom H, Boers GH, Banerjee R: Alleviation of intrasteric inhibition by the pathogenic activation domain mutation, D444N, in human cystathionine beta-synthase. Biochemistry. 2002 Oct 1;41(39):11832-7. [12269827 ]
Target Details
4. S-adenosylmethionine decarboxylase proenzyme
General Function:
Putrescine binding
Specific Function:
Essential for biosynthesis of the polyamines spermidine and spermine. Promotes maintenance and self-renewal of embryonic stem cells, by maintaining spermine levels (By similarity).
Gene Name:
AMD1
Uniprot ID:
P17707
Molecular Weight:
38339.335 Da
References
  1. Dudkowska M, Stachurska A, Grzelakowska-Sztabert B, Manteuffel-Cymborowska M: Up-regulation of spermidine/spermine N1-acetyltransferase (SSAT) expression is a part of proliferative but not anabolic response of mouse kidney. Acta Biochim Pol. 2002;49(4):969-77. [12545203 ]
  2. Ndjonka D, Zou Y, Bi X, Woster P, Walter RD, Luersen K: The activator-binding site of Onchocerca volvulus S-adenosylmethionine decarboxylase, a potential drug target. Biol Chem. 2003 Aug;384(8):1195-201. [12974388 ]
  3. Notari S, Lucchi R, Traversa U, Fabbri E, Poli A: Reversible changes in goldfish brain polyamine concentrations and synthetic enzymes after cold exposure. Brain Res. 2004 May 1;1006(2):241-7. [15051528 ]
  4. Yerlikaya A, Stanley BA: Structural basis for the inactivation of AdoMetDC K12R mutant. Protein Pept Lett. 2006;13(3):313-7. [16515461 ]
Target Details
5. S-adenosylmethionine synthase isoform type-2
General Function:
Methionine adenosyltransferase activity
Specific Function:
Catalyzes the formation of S-adenosylmethionine from methionine and ATP.
Gene Name:
MAT2A
Uniprot ID:
P31153
Molecular Weight:
43660.37 Da
References
  1. Mudd SH, Cerone R, Schiaffino MC, Fantasia AR, Minniti G, Caruso U, Lorini R, Watkins D, Matiaszuk N, Rosenblatt DS, Schwahn B, Rozen R, LeGros L, Kotb M, Capdevila A, Luka Z, Finkelstein JD, Tangerman A, Stabler SP, Allen RH, Wagner C: Glycine N-methyltransferase deficiency: a novel inborn error causing persistent isolated hypermethioninaemia. J Inherit Metab Dis. 2001 Aug;24(4):448-64. [11596649 ]
  2. Farrar C, Clarke S: Altered levels of S-adenosylmethionine and S-adenosylhomocysteine in the brains of L-isoaspartyl (D-Aspartyl) O-methyltransferase-deficient mice. J Biol Chem. 2002 Aug 2;277(31):27856-63. Epub 2002 May 22. [12023972 ]
  3. Martinez-Chantar ML, Latasa MU, Varela-Rey M, Lu SC, Garcia-Trevijano ER, Mato JM, Avila MA: L-methionine availability regulates expression of the methionine adenosyltransferase 2A gene in human hepatocarcinoma cells: role of S-adenosylmethionine. J Biol Chem. 2003 May 30;278(22):19885-90. Epub 2003 Mar 26. [12660248 ]
  4. Martinez-Chantar ML, Garcia-Trevijano ER, Latasa MU, Martin-Duce A, Fortes P, Caballeria J, Avila MA, Mato JM: Methionine adenosyltransferase II beta subunit gene expression provides a proliferative advantage in human hepatoma. Gastroenterology. 2003 Apr;124(4):940-8. [12671891 ]
Target Details
6. Catechol O-methyltransferase
General Function:
O-methyltransferase activity
Specific Function:
Catalyzes the O-methylation, and thereby the inactivation, of catecholamine neurotransmitters and catechol hormones. Also shortens the biological half-lives of certain neuroactive drugs, like L-DOPA, alpha-methyl DOPA and isoproterenol.
Gene Name:
COMT
Uniprot ID:
P21964
Molecular Weight:
30036.77 Da
References
  1. Lee BW, Sun HG, Zang T, Kim BJ, Alfaro JF, Zhou ZS: Enzyme-catalyzed transfer of a ketone group from an S-adenosylmethionine analogue: a tool for the functional analysis of methyltransferases. J Am Chem Soc. 2010 Mar 24;132(11):3642-3. doi: 10.1021/ja908995p. [20196537 ]
  2. Rutherford K, Le Trong I, Stenkamp RE, Parson WW: Crystal structures of human 108V and 108M catechol O-methyltransferase. J Mol Biol. 2008 Jun 27;380(1):120-30. doi: 10.1016/j.jmb.2008.04.040. Epub 2008 Apr 23. [18486144 ]
Target Details
7. Methionine synthase
General Function:
Zinc ion binding
Specific Function:
Catalyzes the transfer of a methyl group from methyl-cobalamin to homocysteine, yielding enzyme-bound cob(I)alamin and methionine. Subsequently, remethylates the cofactor using methyltetrahydrofolate (By similarity).
Gene Name:
MTR
Uniprot ID:
Q99707
Molecular Weight:
140525.91 Da
References
  1. Wolthers KR, Scrutton NS: Protein interactions in the human methionine synthase-methionine synthase reductase complex and implications for the mechanism of enzyme reactivation. Biochemistry. 2007 Jun 12;46(23):6696-709. Epub 2007 May 4. [17477549 ]
Target Details
8. Phenylethanolamine N-methyltransferase
General Function:
Phenylethanolamine n-methyltransferase activity
Specific Function:
Converts noradrenaline to adrenaline.
Gene Name:
PNMT
Uniprot ID:
P11086
Molecular Weight:
30854.745 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Dissociation4.8 uMNot AvailableBindingDB 28422
References
  1. Wu Q, Gee CL, Lin F, Tyndall JD, Martin JL, Grunewald GL, McLeish MJ: Structural, mutagenic, and kinetic analysis of the binding of substrates and inhibitors of human phenylethanolamine N-methyltransferase. J Med Chem. 2005 Nov 17;48(23):7243-52. [16279783 ]
Target Details
9. Protein arginine N-methyltransferase 1
General Function:
Protein-arginine omega-n asymmetric methyltransferase activity
Specific Function:
Arginine methyltransferase that methylates (mono and asymmetric dimethylation) the guanidino nitrogens of arginyl residues present in proteins such as ESR1, histone H2, H3 and H4, PIAS1, HNRNPA1, HNRNPD, NFATC2IP, SUPT5H, TAF15 and EWS. Constitutes the main enzyme that mediates monomethylation and asymmetric dimethylation of histone H4 'Arg-4' (H4R3me1 and H4R3me2a, respectively), a specific tag for epigenetic transcriptional activation. Together with dimethylated PIAS1, represses STAT1 transcriptional activity, in the late phase of interferon gamma (IFN-gamma) signaling. May be involved in the regulation of TAF15 transcriptional activity, act as an activator of estrogen receptor (ER)-mediated transactivation, play a key role in neurite outgrowth and act as a negative regulator of megakaryocytic differentiation, by modulating p38 MAPK pathway. Methylates FOXO1 and retains it in the nucleus increasing its transcriptional activity.
Gene Name:
PRMT1
Uniprot ID:
Q99873
Molecular Weight:
41515.2 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
IC5012 uMNot AvailableBindingDB 28422
References
  1. Dowden J, Hong W, Parry RV, Pike RA, Ward SG: Toward the development of potent and selective bisubstrate inhibitors of protein arginine methyltransferases. Bioorg Med Chem Lett. 2010 Apr 1;20(7):2103-5. doi: 10.1016/j.bmcl.2010.02.069. Epub 2010 Feb 20. [20219369 ]
Target Details
10. Protein-L-isoaspartate(D-aspartate) O-methyltransferase
General Function:
Protein-l-isoaspartate (d-aspartate) o-methyltransferase activity
Specific Function:
Catalyzes the methyl esterification of L-isoaspartyl and D-aspartyl residues in peptides and proteins that result from spontaneous decomposition of normal L-aspartyl and L-asparaginyl residues. It plays a role in the repair and/or degradation of damaged proteins. Acts on EIF4EBP2, microtubule-associated protein 2, calreticulin, clathrin light chains a and b, Ubiquitin carboxyl-terminal hydrolase isozyme L1, phosphatidylethanolamine-binding protein 1, stathmin, beta-synuclein and alpha-synuclein.
Gene Name:
PCMT1
Uniprot ID:
P22061
Molecular Weight:
24636.21 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory48 uMNot AvailableBindingDB 28422
Inhibitory164 uMNot AvailableBindingDB 28422
References
  1. Barton DH, Gero SD, Lawrence F, Robert-Gero M, Quiclet-Sire B, Samadi M: Total synthesis of uracil analogues of sinefungin. J Med Chem. 1992 Jan;35(1):63-7. [1732534 ]