Molecular Pharmacology, Vol 4, 44-52, Copyright © 1968 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of Yeast Alcohol Dehydrogenase by N¹-Benzylpyridinium Chlorides

¹ Department of Biochemistry, University of Tennessee, Knoxville, Tennessee 37916

Ten N¹-benzylpyridinium chlorides were prepared and studied as inhibitors of the yeast alcohol dehydrogenase-catalyzed oxidation of ethanol. The inhibitors, although containing a variety of functional groups substituted on the pyridinium ring, all inhibited this reaction and in each case the inhibition observed was competitive with respect to NAD⁺. Interactions of these inhibitors with the "pyridinium ring" region of the NAD⁺ binding site was suggested by the competitive nature of the inhibition and the simultaneous bintling of all the inhibitors with adenylic acid. Varying the substituent group on the pyridinium ring did not alter significantly the binding properties of the N¹-benzyl derivatives except in those cases where charged groups were employed. In comparison to the binding of N¹-benzylnicotinamide chloride, N¹-benzyl-3-carboxyl-pyridinium chloride was demonstrated to be bound more poorly. N¹-Benzyl-3-aminomethylpyridinium chloride, on the other hand, was found to be a better inhibitor than N¹-benzylnicotinamide chloride.

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ACKNOWLEDGMENT This is contribution 42 from the Department of Biochemistry, The University of Tennessee. The work was supported by Research Grant AM-08812-03 from the United States Public Health Service.