Nutr Res Pract.  2008 Dec;2(4):195-199. 10.4162/nrp.2008.2.4.195.

In vitro inhibition of 10-formyltetrahydrofolate dehydrogenase activity by acetaldehyde

• Mun JA
• Doh E
• Min H

• KMID: 2139191
• DOI: http://doi.org/10.4162/nrp.2008.2.4.195

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 IC50 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.

Keyword

Ethanol toxicity; acetaldehyde; 10-formyltetrahydrofolate dehydrogenase/hydrolase; folate

MeSH Terms

Acetaldehyde
Alcoholism
Animals
Animals, Laboratory
Ethanol
Folic Acid
Humans
Inhibitory Concentration 50
Leucovorin
Liver
Oxidoreductases
Oxidoreductases Acting on CH-NH Group Donors
Rats
Acetaldehyde
Ethanol
Folic Acid
Leucovorin
Oxidoreductases
Oxidoreductases Acting on CH-NH Group Donors

Figure

• 

  Fig. 1 Effects of temperature on the dehydrogenase activity of FDH during incubation in the presence of acetaldehyde in vitro. Purified FDH was incubated in the presence of various concentrations of acetaldehyde at 4℃ and 37℃. FDH dehydrogenase activity was estimated by THF production at 300 nm in the presence of NADP+ and then by subtracting hydrolytic rate from total rate. Each point represents the mean of triplicate estimates of THF production and expressed as a percentage with respect to a control containing equivalent enzyme concentration and no acetaldehyde.

• 

  Fig. 2 Effects of acetaldehyde on FDH dehydrogenase activity over time in vitro. Purified FDH was incubated in the presence of 2 mM or 6 mM acetaldehyde at 4℃. FDH dehydrogenase activity was estimated by THF production at 300 nm in the presence of NADP+ and then by subtracting hydrolytic rate from total rate. Each point represents the mean of triplicate estimates of THF production.

• 

  Fig. 3 Effects of acetaldehyde concentration on the dehydrogenase and hydrolase activities of FDH in vitro. Purified FDH was incubated in the presence of various concentrations of acetaldehyde at 4℃. Dehydrogenase (DH) activity of FDH was estimated by THF production at 300 nm in the presence of NADP+ and then by subtracting hydrolytic rate from total rate. Hydrolase activity was estimated by THF production at 300 nm in the absence of NADP+. Each point is the mean of triplicate estimates of the activities and expressed as a percentage activity with respect to a control containing equivalent enzyme concentration and no acetaldehyde.

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