Methionine metabolic pathway in alcoholic liver injury

PURPOSE OF REVIEW: To outline recent advances in the understanding of the consequences of the alterations in the methionine metabolic pathway and to present new treatment options for alcoholic liver disease (ALD). RECENT FINDINGS: ALD is a major healthcare problem worldwide. Findings in many laboratories, including ours, have demonstrated that ethanol consumption impairs several of the multiple steps in methionine metabolism that ultimately impairs the activity of many methyltransferases critical for normal functioning of the liver. Recent studies buttress the important role genetics may play in the development and progression of alcoholic liver injury. Treatment modalities using two important metabolites of the pathway, S-adenosylmethionine and betaine, have been shown to attenuate ethanol-induced liver injury in a variety of experimental models of liver disease. S-adenosylmethionine has been used in several clinical studies; however, the outcomes have been unclear and its efficacy in liver diseases continues to be debated. To date, no clinical trials have been conducted for treatment of ALD with betaine. SUMMARY: Future treatment modalities for ALD should consider loss-of-function polymorphisms in the enzymes of the methionine metabolic and related pathways. Further new treatment modalities for ALD should consider supplementation with betaine that may prove to be a promising therapeutic agent.