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

Kusum Kharbanda, A. J. Barak

Research output: Chapter in Book/Report/Conference proceedingChapter

8 Citations (Scopus)

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 - Jan 1 2005

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Metabolism
S-Adenosylmethionine
Methionine
Liver
Homocysteine
Ethanol
Betaine
Defects
Wounds and Injuries
choline oxidase
Metabolites
Hepatocytes
Betaine-Homocysteine S-Methyltransferase
S-Adenosylhomocysteine
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
Alcoholic Liver Diseases
Methylation
Poisons
Enzymes
Choline

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Kharbanda, 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

Defects in Methionine Metabolism : Its Role in Ethanol-induced Liver Injury. / Kharbanda, Kusum; Barak, A. J.

Comprehensive Handbook of Alcohol Related Pathology. Vol. 2-3 Elsevier Inc., 2005. p. 735-747.

Research output: Chapter in Book/Report/Conference proceedingChapter

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