EFFECT OF CHRONIC ALCOHOL INGESTION ON HEPATIC FOLATE DISTRIBUTION INTHE RAT

The mechanism by which ethanol impairs folate metabolism remains uncer tain. In the present study, we used our new technique (affinity/HPLC) for folate analysis to study the effect of chronic alcohol ingestion o n the content and distribution of folates in livers. Twelve male Sprag ue-Dawley rats (180 g) were divided into two groups, and fed for 4 wee ks with Lieber-DeCarli semi-liquid isocaloric diets, with and without 5% ethanol. Livers were extracted in boiling, pH 9.3 berate buffers co ntaining ascorbate/dithioerythritol. Folates in the supernatant fracti ons were purified by affinity chromatography and analyzed using ion pa ir high performance liquid chromatography. The data obtained showed th at hepatic folate distribution in alcohol-treated rats differed from t hat of control animals in two ways. Livers from the ethanol-fed rats, when compared with those from control rats, exhibited increases in the percent concentrations of methylated tetrahydrofolates (21.46 +/- 2.2 1 vs 14.8 +/- 1.23), decreases in the percent concentrations of formyl ated tetrahydrofolates (25.62 +/- 4.02 vs 46.18 +/- 2.65) and higher c oncentrations of unsubstituted tetrahydrofolates (52.91 +/- 3.84 vs 38 .88 +/- 2.50). In addition, alcohol ingestion was associated with long er glutamate chains of the folate molecules, characterized by lower re lative concentrations of pentaglutamyl folates (29 vs 48%), and higher relative concentrations of hexa-and heptaglutamyl folates (55 vs 46% and 15 vs 6%) when compared with controls. The data are discussed in r elation to the possibility that alcohol exerts its effect through: (1) inhibition of B12-dependent methyl transfer from methyltetrahydrofola te to homocysteine; (2) diversion of formylated tetrahydrofolates towa rd serine synthesis; and (3) interaction of acetaldehyde with tetrahyd rofolates, thereby interfering with folate coenzyme metabolism.