S-adenosyl-L-methionine (SAMe), a molecule naturally present in several body tissues and fluids, is produced, by SAMe
synthetase, from
ATP and
methionine. SAMe has a fundamental role, as methyl group donor, in transmethylation reactions in which the synthesis of membrane
phospholipids (especially
phosphatidylcholine) is mandatory for the maintenance of membrane fluidity. Another metabolic pathway involving SAMe, transsulphuration, is initiated with the release of -CH3 from the molecule and the formation of S-Adenosyl-
homocysteine and then
homocysteine and
cysteine, a precursor of
glutathione the main cellular
antioxidant, responsible of detoxification of various compounds and
xenobiotics. At last SAMe is implicated in aminopropylation process for the
polyamine synthesis. The development of stable double
salt of
p-toluene sulphonic acid and sulphuric
acid of SAMe enables the clinical use of the
drug, as a therapeutical agent, for the treatment of a number of
liver dysfunctions. In various animal and human models, including controlled trials, it has been demonstrated that SAMe can ameliorate some biochemical parameters and
pruritus in
cholestasis induced by a range of compounds (i.e. oestrogens, lithocolate, etc) and in
intrahepatic cholestasis superimposed to chronic
liver disease. Concerning alcohol toxicity, SAMe prevents, in
ethanol fed baboons, depletion of
glutathione levels, normalizes the mitochondrial
enzymes and improves the histological hepatic lesions. In human healthy volunteers it has been recently demonstrated that SAMe, after
ethanol ingestion, significantly lowers plasma concentration of
ethanol and
acetaldehyde as well. Finally, SAMe has been proposed, instead of
N-acetylcysteine, as precursor of
glutathione, in patients who present late after ingestion of an overdose of
paracetamol.