On the Role of Alcohol Dehydrogenase in ω‐Oxidation of Fatty Acids

Abstract

Rat and horse liver alcohol dehydrogenase was found to oxidize ω2‐hydroxyfatty acids into the corresponding oxofatty acids but showed no significant activity towards ω1‐hydroxyfatty acids. However, ω1‐hydroxyfatty acids were oxidized into the corresponding dicarboxylic acids by a combination of horse or rat liver alcohol dehydrogenase with rat liver aldehyde dehydrogenase. The ratio between ω‐hydroxyfatty acid dehydrogenase activity and ethanol dehydrogenase activity increased about two‐fold through the steps used in the preparation of alcohol dehydrogenase from rat liver. Oxidation of 17‐dl‐hydroxystearic acid by rat liver alcohol dehydrogenase was inhibited by pyrazol, ethanol and 3β‐Lhydroxy‐5β‐cholanoic acid. Oxidation of ethanol and 3β‐hydroxy‐5β‐cholanoic acid by rat liver alcohol dehydrogenase was inhibited by ω‐hydroxy‐fatty acids. Long‐chain ω1‐ and ω2‐hydroxyfatty acids were oxidized by rat liver alcohol dehydrogenase much more efficiently than medium‐chain ω1‐ and ω2‐hydroxyfatty acids and the Km, values for oxidation of the long‐chain ω‐hydroxyfatty acids were 10–40 μM. The rate of oxidation of 17‐l‐hydroxystearic acid by rat and horse liver alcohol dehydrogenase was faster than that of oxidation of 17‐d‐hydroxystearic acid. Experiments with different monohydroxylated stearic acids as substrates for rat liver alcohol dehydrogenase showed that significant activity appeared when the distance between the hydroxyl group and the carboxyl group was more than 12 carbon units. The activity increased with increasing distance between the hydroxyl group and the carboxyl group. Lauryl alcohol but not stearyl alcohol was oxidized by rat liver alcohol dehydrogenase to a significant extent. Copyright © 1972, Wiley Blackwell. All rights reserved