S-Adenosyl methionine
Names | |
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Systematic IUPAC name
(2S)-2-Amino-4-[(S)-{[(2S,3S,4R,5R)-5-(4-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methyl}methylsulfaniumyl]butanoate | |
Other names
S-Adenosyl-L-methionine; SAM-e; SAMe, AdoMet, Heparab (India), ademethionine
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Identifiers | |
3D model (
JSmol ) |
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ChEMBL | |
ChemSpider | |
ECHA InfoCard
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100.045.391 |
KEGG | |
MeSH | S-Adenosylmethionine |
PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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Properties | |
C15H22N6O5S | |
Molar mass | 398.44 g·mol−1 |
Pharmacology | |
A16AA02 (WHO) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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S-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common
In
Structure
S-Adenosyl methionine consists of the adenosyl group attached to the sulfur of methionine, providing it with a positive charge. It is synthesized from ATP and methionine by S-Adenosylmethionine synthetase enzyme through the following reaction:
- ATP + L-methionine + H2O diphosphate+ S-adenosyl-L-methionine
The sulfonium functional group present in S-adenosyl methionine is the center of its peculiar reactivity. Depending on the enzyme, S-adenosyl methionine can be converted into one of three products:
- adenosyl radical, which converts to deoxyadenosine (AdO): classic rSAM reaction, also cogenerates methionine
- S-adenosyl homocysteine, releasing methyl radical
- methylthioadenosine(SMT), homoalanine radical
Biochemistry
SAM cycle
The reactions that produce, consume, and regenerate SAM are called the SAM cycle. In the first step of this cycle, the SAM-dependent
Radical SAM enzymes
A large number of enzymes cleave SAM reductively to produce radicals:
The radical intermediates generated by these enzymes perform a wide variety of unusual chemical reactions. Examples of radical SAM enzymes include
Deficiencies in radical SAM enzymes have been associated with a variety of diseases including
Polyamine biosynthesis
Another major role of SAM is in polyamine biosynthesis. Here, SAM is decarboxylated by adenosylmethionine decarboxylase (EC 4.1.1.50) to form S-adenosylmethioninamine. This compound then donates its n-propylamine group in the biosynthesis of polyamines such as spermidine and spermine from putrescine.[9]
SAM is required for cellular growth and repair. It is also involved in the biosynthesis of several hormones and neurotransmitters that affect mood, such as
Therapeutic uses
Osteoarthrtitis pain
As of 2012, the evidence was inconclusive as to whether SAM can mitigate the pain of osteoarthritis; clinical trials that had been conducted were too small from which to generalize.[12]
Liver disease
The SAM cycle has been closely tied to the liver since 1947 because people with
Depression
A 2016 Cochrane review concluded that for major depressive disorder, "Given the absence of high quality evidence and the inability to draw firm conclusions based on that evidence, the use of SAMe for the treatment of depression in adults should be investigated further."[16]
A 2020 systematic review found that it performed significantly better than placebo, and had similar outcomes to other commonly used antidepressants (imipramine and escitalopram).[17]
Anti-cancer treatment
SAM has recently been shown to play a role in epigenetic regulation. DNA methylation is a key regulator in epigenetic modification during mammalian cell development and differentiation. In mouse models, excess levels of SAM have been implicated in erroneous methylation patterns associated with diabetic neuropathy. SAM serves as the methyl donor in cytosine methylation, which is a key epigenetic regulatory process.[18] Because of this impact on epigenetic regulation, SAM has been tested as an anti-cancer treatment. In many cancers, proliferation is dependent on having low levels of DNA methylation. In vitro addition in such cancers has been shown to remethylate oncogene promoter sequences and decrease the production of proto-oncogenes.[19] In cancers such as colorectal cancer, aberrant global hypermethylation can inhibit promoter regions of tumor-suppressing genes. Contrary to the former information, colorectal cancers (CRCs) are characterized by global hypomethylation and promoter-specific DNA methylation.[20]
Pharmacokinetics
Oral SAM achieves peak plasma concentrations three to five hours after ingestion of an enteric-coated tablet (400–1000 mg). The half-life is about 100 minutes.[21]
Availability in different countries
In Canada, the UK,
It was introduced as a prescription drug in Italy in 1979, in Spain in 1985, and in Germany in 1989.[24] As of 2012, it was sold as a prescription drug in Russia, India, China, Italy, Germany, Vietnam, and Mexico.[15]
Adverse effects
Gastrointestinal disorder,
Another reported side effect of SAM is insomnia; therefore, the supplement is often taken in the morning. Other reports of mild side effects include lack of appetite, constipation, nausea, dry mouth, sweating, and anxiety/nervousness, but in placebo-controlled studies, these side effects occur at about the same incidence in the placebo groups.[medical citation needed]
Interactions and contraindications
Taking SAM at the same time as some drugs may increase the risk of
SAM can also interact with many antidepressant medications — including
Toxicity
A 2022 study concluded that SAMe could be toxic. Jean-Michel Fustin of
See also
- DNA methyltransferase
- SAM-I riboswitch
- SAM-II riboswitch
- SAM-III riboswitch
- SAM-IV riboswitch
- SAM-V riboswitch
- SAM-VI riboswitch
- List of investigational antidepressants
References
- ^ .
- PMID 26321661.
- S2CID 15567646.
- PMID 10762063.
- PMID 10720211.
- S2CID 23877329.
- PMID 21152342.
- ^ PMID 27145839.
- PMID 16766004.
- PMID 16545107.
- S2CID 11214528.
- PMID 19821403.
- PMID 9175157.
- PMID 22659519.
- ^ PMID 23073625.
- PMID 27727432.
- PMID 32939220.
- PMID 24607226.
- PMID 27688072.
- PMID 28958388.
- ^ a b
Najm WI, Reinsch S, Hoehler F, Tobis JS, Harvey PW (February 2004). "S-Adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: A double-blind cross-over trial. ISRCTN36233495". BMC Musculoskelet Disord. 5: 6. PMID 15102339.
- ^ a b McKie, Robin (10 April 2022). "Biologists warn against toxic SAMe 'health' supplement". The Observer.
- ^ Woolston, Chris (31 December 2020). "What is SAM-e?". HealthDay.
- ^ PMID 12418493.
- PMID 7188181.
- ^ "SAMe - Mayo Clinic". Mayo Clinic.
- ^ a b "S-Adenosyl-L-Methionine (SAMe): In Depth". National Center for Complementary and Integrative Health (NCCIH). January 11, 2017.
- PMID 35383287.
External links
- EINECS number 249-946-8
- Shippy, R Andrew; Mendez, Douglas; Jones, Kristina; Cergnul, Irene; Karpiak, Stephen E (2004). "S-Adenosylmethionine (SAM-e) for the treatment of depression in people living with HIV/AIDS". BMC Psychiatry. 4: 38. PMID 15538952.