Latent inhibitors. Part 3. The inhibition of lactate dehydrogenase and alcohol dehydrogenase by cyclopropane-containing compounds

Abstract

A series of monocyclic and bicyclic cyclopropylmethanols typified by bicyclo[4.1.0]heptan-7-ylmethanol is shown to comprise latent irreversible inhibitors of horse liver alcohol dehydrogenase (E.C.1.1.1.1) with inhibitory properties related to the ability of the inhibitor to bind to the enzyme. The time course of inhibition is biphasic, a property shared by a number of unsaturated aldehydes, ketones, and alcohols. Kinetic studies also suggest that inhibition occurs most effectively during the removal of hydride from the inhibitor as oxidation takes place. Analogous properties were found for the inhibition of lactate dehydrogenase (E.C.1.1.1.27) by cyclopropylglycolic acid.