title: Effect of chronic alcohol ingestion on hepatic folate distribution in the rat.
abstract: The mechanism by which ethanol impairs folate metabolism remains uncertain. In the present study, we used our new technique (affinity/HPLC) for folate analysis to study the effect of chronic alcohol ingestion on the content and distribution of folates in livers. Twelve male Sprague-Dawley rats (180 g) were divided into two groups, and fed for 4 weeks with Lieber-DeCarli semi-liquid isocaloric diets, with and without 5% ethanol. Livers were extracted in boiling, pH 9.3 borate buffers containing ascorbate/dithioerythritol. Folates in the supernatant fractions were purified by affinity chromatography and analyzed using ion pair high performance liquid chromatography. The data obtained showed that hepatic folate distribution in alcohol-treated rats differed from that 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 +/- 2.21 vs 14.8 +/- 1.23), decreases in the percent concentrations of formylated tetrahydrofolates (25.62 +/- 4.02 vs 46.18 +/- 2.65) and higher concentrations of unsubstituted tetrahydrofolates (52.91 +/- 3.84 vs 38.88 +/- 2.50). In addition, alcohol ingestion was associated with longer glutamate chains of the folate molecules, characterized by lower relative 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 relation to the possibility that alcohol exerts its effect through: (1) inhibition of B12-dependent methyl transfer from methyltetrahydrofolate to homocysteine; (2) diversion of formylated tetrahydrofolates toward serine synthesis; and (3) interaction of acetaldehyde with tetrahydrofolates, thereby interfering with folate coenzyme metabolism.
authors.affiliation: USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111.
authors.forename: N
authors.initials: N
authors.lastname: Hidiroglou
authors.forename: M E
authors.initials: ME
authors.lastname: Camilo
authors.forename: H C
authors.initials: HC
authors.lastname: Beckenhauer
authors.forename: D J
authors.initials: DJ
authors.lastname: Tuma
authors.forename: A J
authors.initials: AJ
authors.lastname: Barak
authors.forename: P F
authors.initials: PF
authors.lastname: Nixon
authors.forename: J
authors.initials: J
authors.lastname: Selhub
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000378:metabolism*; D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D050940:Betaine-Homocysteine S-Methyltransferase; D001835:Body Weight; D000431:Ethanol / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D013763:Tetrahydrofolates / Q000302:isolation & purification / Q000378:metabolism*
chemical_list: D013763:Tetrahydrofolates; D000431:Ethanol; D008780:Methyltransferases; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D050940:Betaine-Homocysteine S-Methyltransferase