ABSTRACT
S-adenosylmethionine (SAM) is produced primarily in the liver and plays a vital role in cellular metabolism. Hepatic SAM is synthesized from methionine in a reaction catalyzed by the liver-specific methionine adenosyltransferase I/III (MAT I/III) which is encoded by the MAT1A gene. SAM is the principal biological methyl donor, a precursor for polyamines, and an obligatory intermediate in the trans-sulfuration pathway that generates reduced glutathione (GSH). Accordingly, SAM controls many vital hepatic functions as well as the response to liver injury. The observations from animal models and human studies presented in this review strongly implicate hepatic SAM deficiency as a key component in the development of alcoholic liver disease (ALD) and nonalcoholic fatty liver disease/steatohepatitis (NAFLD/NASH). Also reviewed is the therapeutic potential of SAM in animal and human studies that provide a rationale for its use in the treatment of ALD and NAFLD/NASH.