Ethanol feeding inhibits the activity of hepatic N⁵-methyltetrahydrofolate-homocysteine methyltransferase in the rat

Recent studies in this laboratory have shown that when rats were chronically fed ethanol that N⁵-methyltetrahydrofolate accumulated in the liver and this was accompanied by an increase in activity of betaine-homocysteine methyltransferase along with a reduction hepatic betaine. These data suggested that ethanol must have an influence on methionine metabolism at the level of conversion of homocysteine to methionine. It suggested that the enzyme N⁵-methyltetrahydrofolate-homocysteine methyltransferase must be inhibited in some way and that in compensation the rat liver enzyme betaine-homocysteine methyltransferase (BHMT) is increased in activity to supply methionine. The current study tested this hypothesis. Rats were fed the Lieber-DeCarli ethanol diet for periods of 6 and 31 days and following these periods, the livers were assayed for N⁵-methyltetrahydrofolate-homocysteine methyltransferase. The findings showed that the ethanol feeding reduced the activity of this enzyme significantly in 6 days and the lowering was still in effect at 31 days. It is entirely feasible that this action of ethanol may be the site where ethanol produces a lesion in folate metabolism which has been suspected for years.