Betaine lowers elevated S-adenosylhomocysteine levels in hepatocytes from ethanol-fed rats

Anthony J. Barak, Harriet C. Beckenhauer, Mark E Mailliard, Kusum Kharbanda, Dean J. Tuma

Research output: Contribution to journalArticle

86 Citations (Scopus)

Abstract

Previous studies showed that chronic ethanol administration inhibits methionine synthase activity, resulting in impaired homocysteine remethylation to form methionine. This defect in homocysteine remethylation was shown to increase plasma homocysteine and to interfere with the production of hepatic S-adenosylmethionine (SAM) in ethanol-fed rats. These changes were shown to be reversed by the administration of betaine, an alternative methylating agent. This study was undertaken to determine additional effects of ethanol on methionine metabolism and their functional consequences. The influences of methionine loading and betaine supplementation were also evaluated. Adult Wistar rats were fed ethanol or a control Lieber-DeCarli liquid diet for 4 wk, and metabolites of the methionine cycle were measured in vitro in isolated hepatocytes under basal and methionine-supplemented conditions. S-Adenosylhomocysteine (SAH) concentrations were elevated in hepatocytes isolated from ethanol-fed rats compared with controls and in hepatocytes from both groups when supplemented with methionine. The addition of betaine to the methionine-supplemented incubation media reduced the elevated SAH levels. The decrease in the intracellular SAH:SAM ratio due to ethanol consumption inhibited the activity of the liver-specific SAM-dependent methyltransferase, phosphatidylethanolamine methyltransferase. Our data indicate that betaine, by remethylating homocysteine and removing SAH, overcomes the detrimental effects of ethanol consumption on methionine metabolism and may be effective in correcting methylation defects and treating liver diseases.

Original languageEnglish (US)
Pages (from-to)2845-2848
Number of pages4
JournalJournal of Nutrition
Volume133
Issue number9
StatePublished - Sep 1 2003

Fingerprint

adenosylhomocysteine
S-Adenosylhomocysteine
Betaine
betaine
Methionine
hepatocytes
methionine
Hepatocytes
Ethanol
ethanol
homocysteine
rats
Homocysteine
S-Adenosylmethionine
S-adenosylmethionine
phosphatidylethanolamine N-methyltransferase
Phosphatidylethanolamine N-Methyltransferase
5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
methionine synthase
liquid diet

Keywords

  • Betaine
  • Ethanol
  • Hepatocytes
  • Phosphatidylethanolamine methyltransferase
  • S-adenosylhomocysteine

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

Betaine lowers elevated S-adenosylhomocysteine levels in hepatocytes from ethanol-fed rats. / Barak, Anthony J.; Beckenhauer, Harriet C.; Mailliard, Mark E; Kharbanda, Kusum; Tuma, Dean J.

In: Journal of Nutrition, Vol. 133, No. 9, 01.09.2003, p. 2845-2848.

Research output: Contribution to journalArticle

Barak, Anthony J. ; Beckenhauer, Harriet C. ; Mailliard, Mark E ; Kharbanda, Kusum ; Tuma, Dean J. / Betaine lowers elevated S-adenosylhomocysteine levels in hepatocytes from ethanol-fed rats. In: Journal of Nutrition. 2003 ; Vol. 133, No. 9. pp. 2845-2848.
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