Target type: biologicalprocess
The chemical reactions and pathways involving S-adenosylmethionine, S-(5'-adenosyl)-L-methionine, an important intermediate in one-carbon metabolism. [GOC:go_curators, ISBN:0198506732]
S-adenosylmethionine (SAM) metabolic process is a fundamental biochemical pathway that plays a crucial role in various cellular functions. SAM, also known as AdoMet, is a universal methyl donor and is synthesized from methionine and ATP by the enzyme methionine adenosyltransferase (MAT). It serves as a substrate for a wide range of enzymatic reactions, including methylation, transmethylation, and aminopropylation.
**Methylation Reactions:** SAM is a key methyl donor in numerous methylation reactions, which involve the transfer of a methyl group (CH3) from SAM to various substrates, including DNA, RNA, proteins, lipids, and small molecules. These reactions are essential for diverse cellular processes such as gene expression regulation, DNA replication and repair, signal transduction, and neurotransmission.
**Transmethylation Reactions:** In transmethylation reactions, SAM donates its methyl group to another molecule, often a protein, to modify its structure and function. This process plays a role in various cellular processes, including protein folding, enzyme activity, and cell signaling.
**Aminopropylation Reactions:** SAM also participates in aminopropylation reactions, where a 3-aminopropyl group is transferred from SAM to a substrate. This reaction is involved in the biosynthesis of polyamines, which are essential for cell growth and proliferation.
**SAM Cycle:** The SAM metabolic process is a cyclical pathway where SAM is continuously synthesized and regenerated. After donating its methyl group, SAM is converted to S-adenosylhomocysteine (SAH), which is then hydrolyzed to homocysteine and adenosine. Homocysteine can be recycled back to methionine via the transsulfuration pathway, completing the cycle.
**Regulation of SAM Metabolism:** The synthesis and degradation of SAM are tightly regulated to ensure an appropriate supply of this essential metabolite. The activity of MAT, the enzyme responsible for SAM synthesis, is regulated by several factors, including substrate availability, product inhibition, and allosteric regulation. The levels of SAM and SAH also influence the activity of other enzymes involved in SAM metabolism.
**Clinical Significance:** Disruptions in SAM metabolism are associated with various human diseases, including cancer, cardiovascular disease, neurodegenerative disorders, and liver disease. Deficiencies in SAM can lead to impaired methylation reactions, which can contribute to the development of these diseases. Conversely, elevated levels of SAH can inhibit methylation reactions and have detrimental effects on cellular function.
**Therapeutic Applications:** SAM is used as a dietary supplement and a therapeutic agent for various conditions. It is believed to have beneficial effects on mood, cognitive function, and liver health. SAM is also being investigated as a potential treatment for cancer, Alzheimer's disease, and other diseases associated with impaired methylation.'
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Protein | Definition | Taxonomy |
---|---|---|
DNA (cytosine-5)-methyltransferase 3A | A DNA (cytosine-5)-methyltransferase 3A that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9Y6K1] | Homo sapiens (human) |
Glycine N-methyltransferase | A glycine N-methyltransferase that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q14749] | Homo sapiens (human) |
Compound | Definition | Classes | Roles |
---|---|---|---|
procainamide | procainamide : A benzamide that is 4-aminobenzamide substituted on the amide N by a 2-(diethylamino)ethyl group. It is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias. Procainamide: A class Ia antiarrhythmic drug that is structurally-related to PROCAINE. | benzamides | anti-arrhythmia drug; platelet aggregation inhibitor; sodium channel blocker |
dichlone | dichlone: structure | ||
sinefungin | adenosines; non-proteinogenic alpha-amino acid | antifungal agent; antimicrobial agent | |
5,5'-methylenedisalicylic acid | 5,5'-methylenedisalicylic acid: inhibits attachment of ribosomes to microsomal membranes; RN given refers to parent cpd; structure in first source & Merck Index, 9th ed, #5934 | ||
s-adenosylhomocysteine | S-adenosyl-L-homocysteine : An organic sulfide that is the S-adenosyl derivative of L-homocysteine. S-Adenosylhomocysteine: 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions. | adenosines; amino acid zwitterion; homocysteine derivative; homocysteines; organic sulfide | cofactor; EC 2.1.1.72 [site-specific DNA-methyltransferase (adenine-specific)] inhibitor; EC 2.1.1.79 (cyclopropane-fatty-acyl-phospholipid synthase) inhibitor; epitope; fundamental metabolite |
rg108 | RG108: DNA methyltransferase inhibitor; structure in first source | indolyl carboxylic acid | |
genistein | 7-hydroxyisoflavones | antineoplastic agent; EC 5.99.1.3 [DNA topoisomerase (ATP-hydrolysing)] inhibitor; geroprotector; human urinary metabolite; phytoestrogen; plant metabolite; tyrosine kinase inhibitor | |
sgi-1027 | SGI-1027: inhibits DNA methyltransferase 1; structure in first source | ||
gsk343 | GSK343 : A member of the class of indazoles that is 1-isopropyl-1H-indazole-4-carboxamide in which the nitrogen of the carboxamide group is substituted by a (6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl group and in which the indazole ring is substituted at position 6 by a 2-(4-methylpiperazin-1-yl)pyridin-4-yl group. A highly potent and selective EZH2 inhibitor (IC50 = 4 nM). GSK343: an EZH2 methyltransferase inhibitor | aminopyridine; indazoles; N-alkylpiperazine; N-arylpiperazine; pyridone; secondary carboxamide | antineoplastic agent; apoptosis inducer; EC 2.1.1.43 (enhancer of zeste homolog 2) inhibitor |