S- adenosyl methionine

Structural formula
General
Surname	S- adenosyl methionine
other names	SAM; SAMe; AdoMet; S- adenosyl- L- methionine; Ademetionine ( INN );
Molecular formula	C 15 H 22 N 6 O 5 S
External identifiers / databases
EC number	249-946-8
ECHA InfoCard	100.045.391
PubChem	34755
ChemSpider	31982
DrugBank	DB00118
Wikidata	Q27135598
Drug information
ATC code	A16 AA02
properties
Molar mass	398.44 g mol −1
safety instructions
	Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS hazard labeling ; no classification available
	As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

S -Adenosylmethionin shortly SAM called or AdoMet, is a chemical compound from the class of sulfonium - Betaine . SAM is a keyproductin the metabolism of the amino acid methionine and is produced by a reaction of methionine with adenosine triphosphate (ATP).

In metabolism SAM acts as a methyl donor , which is itself about S -Adenosylhomocystein to adenosine and homocysteine hydrolyzed is. Homocysteine can be remethylated again to methionine or broken down into the amino acid cysteine .

history

Giulio Cantoni discovered S- adenosyl methionine in 1952 and researched its importance and chemistry. Its importance as a medicinal substance was only discovered in the last few years. In the US , S-adenosyl methionine is sold as a dietary supplement. This was made possible by the Dietary Supplement Health and Education Act of 1999. This law allows dietary supplements to bypass the Food and Drug Administration (FDA).

In Germany, adenosyl methionine is used as a medicinal substance according to the drug prescription regulation, a prescription drug, adenosyl methionine-containing drugs require a prescription regardless of the dose. Adenosylmethionine was approved in Germany under the name Gumbaral for the treatment of pain in irritable conditions in mild to moderate degenerative joint diseases such as osteoarthritis and was on the market until 2012. Whether adenosylmethionine preparations can be placed on the market in Germany as food (e.g. food supplements ) must be checked on a case-by-case basis and is the responsibility of the responsible authorities. There are numerous substances that are used in both medicines and food. Each product has to be checked for itself and a decision has to be made on the classification. In June 2018, a preparation was denied marketability as a dietary supplement.

biosynthesis

Biosynthetic pathway to SAM

SAM is synthesized in the cells from methionine and ATP by the enzyme methionine adenosyl transferase in the presence of divalent cations such as Mg ²⁺ , Co ²⁺ or Mn ²⁺ . In the case of genetically modified Escherichia coli strains, the presence of certain monovalent metal cations resulted in a marked stimulation of SAM production.

Properties and biological importance

The highly reactive methyl group on the sulfonium group of the SAM is involved in what is known as transmethylation in the metabolism, in which a methyl group is transferred or introduced. These reactions are catalyzed by enzymes called methyltransferases that use SAM as a substrate . Such transmethylations are important steps in the biosynthesis of various neurotransmitters , such as adrenaline or acetylcholine . The phosphatidylcholines, better known as lecithin, also require SAM for their representation. The neurotransmitter histamine is u. a. inactivated by the SAM-dependent histamine- N -methyltransferase. SAM also plays an important role in DNA methylation by DNA methyltransferases in eukaryotes .

Medical application

The broad spectrum of action of SAM as a drug includes the treatment of depression , arthritis and liver disease .

Side effects

The following side effects may occur during treatment with SAM: stomach upset, diarrhea, anxiety, manic symptoms, headache, insomnia and allergic reactions . The effects occurring after long-term therapy are unknown.

Induction of manic symptoms

People with bipolar disorder are at risk of developing manic symptoms after taking SAM , as is the case with other antidepressants . Clinical studies have also shown that oral or injected administration of the compound can cause manic symptoms even in patients without previously diagnosed bipolar disorder.

Individual evidence

↑ WHO: Supplement to WHO Chronicals, 1984, Vol. 38, No. 6 (List 24).
↑ This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.
↑ G. Eisenbrand (Ed.), P. Schreier (Ed.): RÖMPP Lexikon Lebensmittelchemie. 2nd edition, 2006, Thieme-Verlag, ISBN 978-3-13-736602-7 , p. 239.
↑ ^a ^b Kirschler, Julia Nina: Influence of the cofactor NAD + / NADH on cAMP binding to the S-adenosyl-L-homocysteine hydrolase. Dissertation, University of Tübingen, 2006. urn : nbn: de: bsz: 21-opus-25274
↑ ^a ^b Agency for Healthcare Research and Quality : S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease (PDF; 64 kB), Evidence Report / Technology Assessment, Number 64 (August 2012).
↑ Appendix 1 - Substances and preparations according to § 1 No. 1 , AMVV.
↑ ^a ^b Ademetionin ist Arzneimittel , apotheke adhoc, June 21, 2018.
↑ Markham et al. (1980): S-adenosylmethionine synthetase from Escherichia coli, J Biol Chem 255 (19): 9082-9092; PMID 6251075 .
↑ Sandra Christine von Hippel: The influence of hypoxia on methylations . Dissertation, 2006.
↑ Najm, WI et al. (2004): S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. [ISRCTN36233495]. In: BMC Musculoskeleton. Disord. Vol. 5, p. 6 ( PMID 15102339 ; doi : 10.1186 / 1471-2474-5-6 ).
↑ Ivan Goldberg: S-adenosyl-L-methionine as an antidepressant (Results of a MEDLINE Search) . In: Dr. Ivan's Depression Central . May 27, 2006. Retrieved February 7, 2011.

[1] WHO: Supplement to WHO Chronicals, 1984, Vol. 38, No. 6 (List 24).

[NV-2] This substance has either not yet been classified with regard to its hazardousness or a reliable and citable source has not yet been found.

[roempp-lc-3] G. Eisenbrand (Ed.), P. Schreier (Ed.): RÖMPP Lexikon Lebensmittelchemie. 2nd edition, 2006, Thieme-Verlag, ISBN 978-3-13-736602-7 , p. 239.

[Kirschler-4] Kirschler, Julia Nina: Influence of the cofactor NAD + / NADH on cAMP binding to the S-adenosyl-L-homocysteine hydrolase. Dissertation, University of Tübingen, 2006. urn : nbn: de: bsz: 21-opus-25274

[AHRQ-5] Agency for Healthcare Research and Quality : S-Adenosyl-L-Methionine for Treatment of Depression, Osteoarthritis, and Liver Disease (PDF; 64 kB), Evidence Report / Technology Assessment, Number 64 (August 2012).

[6] Appendix 1 - Substances and preparations according to § 1 No. 1 , AMVV.

[adhoc2018-7] Ademetionin ist Arzneimittel , apotheke adhoc, June 21, 2018.

[Markham-8] Markham et al. (1980): S-adenosylmethionine synthetase from Escherichia coli, J Biol Chem 255 (19): 9082-9092; PMID 6251075 .

[Hippel-9] Sandra Christine von Hippel: The influence of hypoxia on methylations . Dissertation, 2006.

[10] Najm, WI et al. (2004): S-adenosyl methionine (SAMe) versus celecoxib for the treatment of osteoarthritis symptoms: a double-blind cross-over trial. [ISRCTN36233495]. In: BMC Musculoskeleton. Disord. Vol. 5, p. 6 ( PMID 15102339 ; doi : 10.1186 / 1471-2474-5-6 ).

[11] Ivan Goldberg: S-adenosyl-L-methionine as an antidepressant (Results of a MEDLINE Search) . In: Dr. Ivan's Depression Central . May 27, 2006. Retrieved February 7, 2011.