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 language||English (US)|
|Title of host publication||Comprehensive Handbook of Alcohol Related Pathology|
|Number of pages||13|
|Publication status||Published - Jan 1 2005|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)