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 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.
Original language | English (US) |
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Pages (from-to) | 1561-1566 |
Number of pages | 6 |
Journal | Biochemical Pharmacology |
Volume | 47 |
Issue number | 9 |
DOIs | |
State | Published - Apr 29 1994 |
Keywords
- acetaldehyde
- ethanol
- folate
- folate analysis
- rats
ASJC Scopus subject areas
- Biochemistry
- Pharmacology