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In vitro inhibition of 10-formyltetrahydrofolate dehydrogenase activity by acetaldehyde  

Mun, Ju-Ae (Department of Food and Nutrition, College of Life Science and Nano Technology, Hannam University)
Doh, Eun-Jin (Department of Biological Sciences, Korea Advanced Institute of Science and Technology)
Min, Hye-Sun (Department of Food and Nutrition, College of Life Science and Nano Technology, Hannam University)
Publication Information
Nutrition Research and Practice / v.2, no.4, 2008 , pp. 195-199 More about this Journal
Abstract
Alcoholism has been associated with folate deficiency in humans and laboratory animals. Previous study showed that ethanol feeding reduces the dehydrogenase and hydrolase activity of 10-formyltetrahydrofolate dehydrogenase (FDH) in rat liver. Hepatic ethanol metabolism generates acetaldehyde and acetate. The mechanisms by which ethanol and its metabolites produce toxicity within the liver cells are unknown. We purified FDH from rat liver and investigated the effect of ethanol, acetaldehyde and acetate on the enzyme in vitro. Hepatic FDH activity was not reduced by ethanol or acetate directly. However, acetaldehyde was observed to reduce the dehydrogenase activity of FDH in a dose- and time-dependent manner with an apparent $IC_{50}$ of 4 mM, while the hydrolase activity of FDH was not affected by acetaldehyde in vitro. These results suggest that the inhibition of hepatic FDH dehydrogenase activity induced by acetadehyde may play a role in ethanol toxicity.
Keywords
Ethanol toxicity; acetaldehyde; 10-formyltetrahydrofolate dehydrogenase/hydrolase; folate;
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