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International Journal of Hepatology
Volume 2012, Article ID 959746, 7 pages
http://dx.doi.org/10.1155/2012/959746
Review Article

Aberrant Hepatic Methionine Metabolism and Gene Methylation in the Pathogenesis and Treatment of Alcoholic Steatohepatitis

Department of Internal Medicine, University of California, Davis, 451 E. Health Sciences Drive, Room 6323, Davis, CA 95616, USA

Received 26 May 2011; Accepted 8 July 2011

Academic Editor: Kusum Kharbanda

Copyright © 2012 Charles H. Halsted and Valentina Medici. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

The pathogenesis of alcoholic steatohepatitis (ASH) involves ethanol-induced aberrations in hepatic methionine metabolism that decrease levels of S-adenosylmethionine (SAM), a compound which regulates the synthesis of the antioxidant glutathione and is the principal methyl donor in the epigenetic regulation of genes relevant to liver injury. The present paper describes the effects of ethanol on the hepatic methionine cycle, followed by evidence for the central role of reduced SAM in the pathogenesis of ASH according to clinical data and experiments in ethanol-fed animals and in cell models. The efficacy of supplemental SAM in the prevention of ASH in animal models and in the clinical treatment of ASH will be discussed.