[Ademetionine: the state of the art and future prospects]

Ademethionine is a biological molecule mostly produced in the liver and involved in several metabolic pathways. Two of them, the transmethylation and the transulfuration pathways, are particularly important for the physiological activity of the hepatocyte. The first one is responsive for the methylation of membrane phospholipids, a reaction which restores the membrane fluidity and therefore allows a normal and correct role of the hepatocyte. The transulfuration pathway leads to the synthesis of compounds such as glutathione and taurine, which are involved in detoxication processes. Patients with liver diseases of different etiology, and especially patients with chronic diseases, have endogenous ademethionine deficiency. This leads to a malfunctioning of the hepatocyte, which ends up to be damaged in its structure and normal activity. Besides the overplus of methionine, not used for the synthesis of ademethionine, gives rise to high plasma levels of the amino acid. The pharmacological supply of ademethionine enhances the two metabolic pathways and avoids the overplus of methionine. The regeneration of transmethylation and transulfuration restores the normal secretory and excretory activity of the liver cell, and therefore leads to a resolution of cholestasis and removal of toxic compounds from liver parenchyma and plasma. Several experimental and clinical studies have shown the therapeutic efficacy and tolerability of ademethionine in hepatopathic patients with cholestasis. Preliminary experimental data suggest for ademethionine not only an anticholestatic effect, but possibly an anti-fibrotic one.