Inhibition of Alcohol Dehydrogenase by Folic Acid and Several of Its Analogs.

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Abstract
Summary Folic acid as well as the anti-folates, aminopterin and amethopterin, arrested ethanol metabolism in homogenates of rat liver by inhibiting alcohol dehydrogenase. Acetaldehyde metabolism was unaffected. In the rat, the conversion of ethanol-1-C14 to C14O2. was slowed by large amounts of folic acid while that of acetate-1-C14 was not. In dogs, folic acid decreased the rate of ethanol disappearance from the plasma. Thus, folic acid inhibited alcohol dehydrogenase in vivo. Purified horse liver alcohol dehydrogenase was inhibited similarly by folic acid, aminopterin, amethopterin, and 4-dimethylamino-4-deoxy-N10-methylpteroylglutamic acid. For these compounds, inhibition started at 3.5 × 10-3 m and was completed at 2 × 10-4 m. Leucovorin did not inhibit the enzyme.