The effect of ethanol on one-carbon metabolism: increased methionine catabolism and lipotrope methyl-group wastage.
Deficiency of choline and methionine produces hepatic steatosis similar to that seen with ethanol, and supplementation with these lipotropes can prevent ethanol-induced fatty liver. These effects are thought to occur through alterations in membrane phospholipid metabolism, but the mechanism whereby this occurs and the precise nature of the changes brought about by ethanol in the interactions of choline and methionine metabolism remain unclear. Through the known effects on hepatic glutathione (which requires as a precursor a product of methionine catabolism), ethanol might affect hepatic one-carbon metabolism, which requires the participation of both methionine and choline in the transfer of methyl groups. This has been investigated with a radiorespirometric technique to assess the in vivo oxidation of the methyl groups of lipotropes and their intermediates in ethnaol- and control-fed rats. Enzyme activities of one-carbon transfer reactions and the hepatic levels of methionine and alpha-aminobutyrate, an end product of methionine catabolism, have been measured. The effect of ethanol feeding on hepatic S-adenosylmethionine and S-adenosylhomocysteine has also been assessed. Ethanol increases the oxidation to carbon dioxide of the methyl group of methionine by a factor of 2.9 (p = 0.002) and produces a 3.6-fold (p = 0.0001) accumulation of alpha-aminobutyrate, indicating a marked increase in methionine catabolism. Hepatic methionine levels are unchanged by ethanol, however, and this may be explained by a dramatic increase in the turnover of the methyl groups of choline and betaine in response to ethanol (times 3.6 and 4.2, respectively, p < 0.003), suggesting greatly increased use of the choline oxidation pathway to remethylate homocysteine through betaine homocysteine methyltransferase.(ABSTRACT TRUNCATED AT 250 WORDS)
Trimble
K C
KC
Department of Clinical Medicine, Trinity College, Dublin, Republic of Ireland.
Molloy
A M
AM
Scott
J M
JM
Weir
D G
DG
D000818:Animals; D002244:Carbon / Q000378:metabolism*; D002794:Choline / Q000378:metabolism; D000431:Ethanol / Q000009:adverse effects*; D005260:Female; D008082:Lipotropic Agents / Q000378:metabolism*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008715:Methionine / Q000378:metabolism*; D008745:Methylation; D051381:Rats; D017208:Rats, Wistar
D008082:Lipotropic Agents; D000431:Ethanol; D002244:Carbon; D008715:Methionine; D002794:Choline