Defects in Methionine Metabolism: Its Role in Ethanol-induced Liver Injury

Kusum K. Kharbanda, A. J. Barak

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Scopus citations

Abstract

This chapter reviews the negative effects of ethanol in multiple steps in methionine metabolism that may lead to liver injury. Alcoholic liver disease is a major health care problem and ethanol consumption is reported to predominantly inhibit the activity of two vital cellular enzymes, methionine synthase and methyl adenosyhransferase involved in remethylating homocysteine and generating S-adenosylmethionine, respectively. By compensation, ethanol increases the activity of the enzyme betaine homocysteine methyltransferase that catalyzes an alternate pathway in methionine metabolism and utilizes hepatic betaine to remethylate homocysteine to form methionine and maintain levels of S-adenosylmethionine, the key-methylating agent. This is true in rat species that generate betaine from choline via choline oxidase. Extended periods of ethanol feeding however, is unable to maintain this alternate pathway. This results in a decrease in the hepatocyte level of S-adenosylmethionine and the most important cellular antioxidant, glutathione and increases in two toxic metabolites, homocysteine and S-adenosylhomocysteine. These changes in the various metabolites of methionine metabolism in turn result in serious functional consequences. These include decreases in the essential methylation reactions by inhibiting various methyhransferases, especially phosphatidylethanolamine methyhransferase, and direct toxicity to hepatocytes and stellate cells.

Original languageEnglish (US)
Title of host publicationComprehensive Handbook of Alcohol Related Pathology
PublisherElsevier Inc.
Pages735-747
Number of pages13
Volume2-3
ISBN (Electronic)9780080502311
ISBN (Print)9780125643702
DOIs
StatePublished - 2005

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Kharbanda, K. K., & Barak, A. J. (2005). Defects in Methionine Metabolism: Its Role in Ethanol-induced Liver Injury. In Comprehensive Handbook of Alcohol Related Pathology (Vol. 2-3, pp. 735-747). Elsevier Inc.. https://doi.org/10.1016/B978-012564370-2/50059-3