Effects of chronic ethanol ingestion and folate deficiency on the activity of 10-formyltetrahydrofolate dehydrogenase in rat liver.
BACKGROUND
We recently observed that ethanol feeding impairs 10-formyltetrahydrofolate (10-FTHF) dehydrogenase (EC 1.5.1.6.) and 10-FTHF hydrolase activity in rats. In the present study, we explored the effects of folate deficiency or sufficiency combined with alcoholic intake on 10-FTHF and possible mechanisms by which chronic ethanol ingestion produces folate deficiency.


METHODS
Sprague-Dawley rats were fed either folate-sufficient (FS) or folate-deficient (FD) diets; with or without ethanol (E) for four weeks. Hepatic 10-FTHF dehydrogenase and hydrolase activity, plasma folate and homocysteine were measured at baseline and after feeding experimental diets.


RESULTS
Liver weight increased slightly with either folate deficiency or ethanol consumption. In rats fed the folate-sufficient diet with ethanol (FSE), plasma folate was decreased slightly (p<0.05) and plasma homocysteine elevated compared to rats fed the FS diet without ethanol. Ethanol did not affect plasma folate and plasma homocysteine in FD rats. Red-blood cell (RBC) folate was increased similarly in rats by ethanol feeding (FSE and FDE>FS and FD). Feeding folate deficient or ethanol (FSE, FD and FDE) diets depressed hepatic activities of 10-FTHF dehydrogenase, which catalyzes the oxidative deformylation of 10-FTHF to tetrahydrofolate (THF) and carbon dioxide. Rats consuming the FDE diet had the lowest enzyme activities of the experimental groups, implying that folate deficiency and ethanol consumption each affect enzyme activity.


CONCLUSIONS
We confirm that ethanol decreases hepatic 10-FTHF dehydrogenase activity and show that this decrease occurs irrespective of folate status. This shows that modulation of 10-FTHF is one possible mechanism by which ethanol intake decreases folate status and affects one-carbon metabolism.
Min
Hyesun
H
Department of Food and Nutrition, Hannam University, Daejeon, Korea.
Im
Eun-Sun
ES
Seo
Jung-Sook
JS
Mun
Ju Ae
JA
Burri
Betty J
BJ
D000581:Amidohydrolases / Q000378:metabolism; D000818:Animals; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D000431:Ethanol / Q000494:pharmacology*; D005492:Folic Acid / Q000097:blood / Q000378:metabolism / Q000652:urine; D005494:Folic Acid Deficiency / Q000201:enzymology*; D006710:Homocysteine / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014815:Vitamins / Q000378:metabolism / Q000652:urine; D015430:Weight Gain / Q000187:drug effects; D000099295:Formyltetrahydrofolate Dehydrogenase
D000581:Amidohydrolases; D002492:Central Nervous System Depressants; D000431:Ethanol; D005492:Folic Acid; D006710:Homocysteine; D000587:Oxidoreductases Acting on CH-NH Group Donors; D014815:Vitamins; D000099295:Formyltetrahydrofolate Dehydrogenase; C056575:formyltetrahydrofolate deformylase protein, rat