Multiple inhibition of yeast alcohol dehydrogenase by heterocyclic nitrogen bases

Abstract

Multiple inhibition studies were carried out with inhibitor pairs composed of various combinations of eleven nitrogen bases previously shown to be competitive inhibitors with respect to NAD + in the yeast alcohol dehydrogenase (alcohol:NAD + oxidoreductase E.C.I.I.I.I.)-catalyzed oxidation of ethanol. In studies of inhibitor pairs in which both inhibitors were adenine derivatives, mutual exclusion was demonstrated. A mutual exclusion was likewise demonstrated in all combinations of inhibitors studied involving phenanthrolines and benzoquinolines. Quinoline, although bound simultaneously to the yeast enzyme with adenine derivatives, shows mutual exclusion when studied with N 1-methylnicotinamide chloride. It was proposed that phenanthrolines and benzoquinolines like quinoline are bound at the “pyridinium ring” region of the NAD + binding site of yeast alcohol dehydrogenase. Charge transfer complexes were observed between N 1-methylnicotinamide chloride and the four adenine derivatives studied.