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targets (6) enzymes (2)
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Identification
Name S-Adenosylmethionine
Accession Number DB00118 (NUTR00052)
Type small molecule
Groups approved, nutraceutical
Description

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)
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
Acylcarnitine
AdoMet
S-adenosyl-L-methionine
SAM
SAM-e
SAMe
Salts Not Available
Brand names
Name Company
Sam-Sulfate Natrol
SAMe Rx-Mood Nature's Plus
Brand mixtures Not Available
Categories
  • Dietary supplement
  • Micronutrient
CAS number 29908-03-0
Weight Average: 399.445
Monoisotopic: 399.145063566
Chemical Formula C15H23N6O5S
InChI Key InChIKey=MEFKEPWMEQBLKI-AIRLBKTGSA-O
InChI
InChI=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
Plain Text
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
SMILES
C[S+](CC[C@H](N)C(O)=O)C[C@H]1O[C@H]([C@H](O)[C@@H]1O)N1C=NC2=C(N)N=CN=C12
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Purines and Purine Derivatives
  • Amino Acids
Substructures
  • Glycerol and Derivatives
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Ethers
  • Sulfoniums
  • Carboxylic Acids and Derivatives
  • Pyrimidines and Derivatives
  • Alcohols and Polyols
  • Imidazoles
  • Heterocyclic compounds
  • Aromatic compounds
  • Purines and Purine Derivatives
  • Amino Acids
  • Furans
  • Cyanamides
  • Cations
Pharmacology
Indication S-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.
Pharmacodynamics S-adenosylmethionine is an intermediate metabolite of methionine. Its involvement in methylation assists in cellular growth and repair, maintains the phospho-bilipid layer in cell membranes. It also helps in the maintenance of the action of several hormones and neurotransmitters that affect mood. Highest concentration are found in the brain and the liver.
Mechanism of action 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.
Absorption S-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.
Volume of distribution Not Available
Protein binding Not Available
Metabolism Significant 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.
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity Irritating to mucus membranes and upper respiratory tract. Can cause CNS depression.
Affected organisms
  • Humans and other mammals
Pathways Not Available
Pharmacoeconomics
Manufacturers Not Available
Packagers
Dosage forms
Form Route Strength
Capsule Oral 100 mg
Capsule Oral 200 mg
Capsule Oral 50 mg
Capsule, delayed release Oral 200 mg
Tablet Oral 100 mg
Tablet Oral 200 mg
Prices
Unit description Cost Unit
Sam-e 400 mg tablet 0.86 USD tablet
CVS Pharmacy sam-e 400 mg tablet 0.79 USD tablet
Sam-e 200 mg tablet 0.59 USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
boiling point 78 °C Not Available
Predicted Properties
Property Value Source
water solubility 1.19e+00 g/l ALOGPS
logP -2 ALOGPS
logP -5.3 ChemAxon
logS -2.6 ALOGPS
pKa (strongest acidic) 1.71 ChemAxon
pKa (strongest basic) 9.41 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 10 ChemAxon
hydrogen donor count 5 ChemAxon
polar surface area 182.63 ChemAxon
rotatable bond count 7 ChemAxon
refractivity 96.23 ChemAxon
polarizability 40.37 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Finkelstein JD, Martin JJ: Homocysteine. Int J Biochem Cell Biol. 2000 Apr;32(4):385-9. Pubmed
  2. Fodinger M, Horl WH, Sunder-Plassmann G: Molecular biology of 5,10-methylenetetrahydrofolate reductase. J Nephrol. 2000 Jan-Feb;13(1):20-33. Pubmed
  3. Roje S: S-Adenosyl-L-methionine: beyond the universal methyl group donor. Phytochemistry. 2006 Aug;67(15):1686-98. Pubmed
  4. Loenen WA: S-adenosylmethionine: jack of all trades and master of everything? Biochem Soc Trans. 2006 Apr;34(Pt 2):330-3. Pubmed
  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. Pubmed
External Links
Resource Link
KEGG Compound C00019 Link_out
PubChem Compound 34756 Link_out
PubChem Substance 46505280 Link_out
ChemSpider 31983 Link_out
ChEBI 15414 Link_out
ChEMBL 15414 Link_out
PharmGKB PA164754994 Link_out
HET SAM Link_out
Drugs.com http://www.drugs.com/cdi/s-adenosylmethionine.html Link_out
PDRhealth http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/sad_0231.shtml Link_out
Wikipedia http://en.wikipedia.org/wiki/S-Adenosylmethionine Link_out
ATC Codes Not Available
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS show (35.5 KB)
Interactions
Drug Interactions
Drug Interaction
Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Ginkgo biloba Additive anticoagulant/antiplatelet effects may increase bleed risk. Concomitant therapy should be avoided.
Ketoprofen Increased risk of bleeding due to additive antiplatelet properties of the two agents. Concomitant therapy should be avoided or monitored carefully for bleeding, bruising and altered mental status, which may be caused by CNS bleeds.
Sulindac S-adenosylmethionine may enhance the anticoagulant effect of sulindac. Increased risk of bleeding, bruising and altered mental status due to CNS bleeds. Concomitant therapy should be avoided.
Tramadol Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Tranylcypromine Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Warfarin Additive anticoagulant effects increase the risk of bleeding. Concomitant therapy should be avoided.
Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and S-adenosylmethionine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Food Interactions Not Available
Targets

1. Glycine N-methyltransferase

Pharmacological action: unknown
Actions: cofactor

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

Organism class: human
UniProt ID: Q14749 Link_out
Gene: GNMT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  5. Uthus EO, Brown-Borg HM: Altered methionine metabolism in long living Ames dwarf mice. Exp Gerontol. 2003 May;38(5):491-8. Pubmed

2. S-adenosylmethionine decarboxylase proenzyme

Pharmacological action: unknown
Actions: cofactor
Organism class: human
UniProt ID: P17707 Link_out
Gene: AMD1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  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. Pubmed
  4. Yerlikaya A, Stanley BA: Structural basis for the inactivation of AdoMetDC K12R mutant. Protein Pept Lett. 2006;13(3):313-7. Pubmed

3. S-adenosylmethionine synthetase isoform type-2

Pharmacological action: unknown
Actions: cofactor

Catalyzes the formation of S-adenosylmethionine from methionine and ATP

Organism class: human
UniProt ID: P31153 Link_out
Gene: MAT2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed

4. Cystathionine beta-synthase

Pharmacological action: unknown
Actions: activator
Organism class: human
UniProt ID: P35520 Link_out
Gene: CBS Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed

5. S-adenosylmethionine synthetase isoform type-1

Pharmacological action: unknown
Actions: cofactor

Catalyzes the formation of S-adenosylmethionine from methionine and ATP

Organism class: human
UniProt ID: Q00266 Link_out
Gene: MAT1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed
  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. Pubmed

6. Catechol O-methyltransferase

Pharmacological action: unknown
Actions: cofactor

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

Organism class: human
UniProt ID: P21964 Link_out
Gene: COMT Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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. Pubmed
  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. Epub 2008 Apr 23. Pubmed
Enzymes

1. Cytochrome P450 2E1

Actions: inhibitor

Metabolizes several precarcinogens, drugs, and solvents to reactive metabolites. Inactivates a number of drugs and xenobiotics and also bioactivates many xenobiotic substrates to their hepatotoxic or carcinogenic forms

UniProt ID: P05181 Link_out
Gene: CYP2E1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Caro AA, Cederbaum AI: Inhibition of CYP2E1 catalytic activity in vitro by S-adenosyl-L-methionine. Biochem Pharmacol. 2005 Apr 1;69(7):1081-93. Pubmed
  2. Cederbaum AI: Hepatoprotective effects of S-adenosyl-L-methionine against alcohol- and cytochrome P450 2E1-induced liver injury. World J Gastroenterol. 2010 Mar 21;16(11):1366-76. Pubmed

2. Spermidine synthase

Actions: substrate
UniProt ID: P19623 Link_out
Gene: SRM Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Cyriac J, Haleem R, Cai X, Wang Z: Androgen regulation of spermidine synthase expression in the rat prostate. Prostate. 2002 Mar 1;50(4):252-61. Pubmed
  2. Dejima H, Kobayashi M, Takasaki H, Takeda N, Shirahata A, Samejima K: Synthetic decarboxylated S-adenosyl-L-methionine as a substrate for aminopropyl transferases. Biol Pharm Bull. 2003 Jul;26(7):1005-8. Pubmed
  3. Franceschetti M, Fornale S, Tassonia A, Zuccherelli K, Mayer MJ, Bagni N: Effects of spermidine synthase overexpression on polyamine biosynthetic pathway in tobacco plants. J Plant Physiol. 2004 Sep;161(9):989-1001. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19