[S-adenosyl-L-methionine (SAMe) and its use in hepatology]

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.