Effect of Folic Acid and Analogues on the Dehydrogenase and Isomerase Activities of Liver Alcohol Dehydrogenase.

Several enzymes possess more than one specific function which can be selectively altered by various agents. For example, glutamic dehydrogenase oxidizes both alanine and glutamic acid (1) ; enzymic activity toward glutamic acid was inhibited by diethylstilbesterol while that toward alanine was stimulated by the same compound. The present communication describes studies on the alterations of the two activities of liver alcohol dehydrogenase (alcohol: NAD oxidoreductase, EC 1.1.1.1): the dehydrogenation of ethanol to acetaldehyde and Dhe isomerization of several aldehydes to ketones (2). The isomerization proceeds at approximately 8 times the rate of the dehydrogenation (2). While folic acid, aminopterin, and amethopterin inhibited dehydrogenase activity (3), these same compounds stimulated the isomerase activity of the dehydrogenase (4). The inhibitions produced by the folates were different from those produced by 1, IO-phenanthroline and %hydroxyquinoline, which have been reported by others to inhibit the dehydrogenase by chelation. Kinetic data showed that inhibition by folic acid was complex, which supports the conclusion that inhibition of dehydrogenase activity was not attributable to chelation of enzymic zinc at the active site. The selective alteration of the two enzymic activities of liver alcohol dehydrogenase by the folates, as well as by 1, IO-phenanthroline, iodoacetate, and p-mercuribenzoate, suggests that these activities take place on distinctly different sites of the enzyme.