498 



2. ANALOGS OF ENZYME REACTION COMPONENTS 



dine inhibits spinal cord NADase 65% at 11 laM. Such inhibition could be 

 due to (1) direct competition with NAD, (2) reaction with E-RPPRA to 

 form a relatively stable complex, thereby depleting free enzyme, or (3) in- 

 hibition by a 3-AcPyr-NAD analog formed. In the case of the INH-NAD 

 analog, the inhibition seems to be mainly of the third type (Zatman et al., 

 1954 b). Nicotinamide deaminase is inhibited quite well by 3-acetylpyri- 

 dine; the inhibition is competitive and 50% at (I)/(S) = 20 (Grossowicz 

 and Halpern, 1956 b). Yeast alcohol dehydrogenase is inhibited directly 

 by substituted pyridines (van Eys, 1956; van Eys and Kaplan, 1957 a). 

 The inhibitions are related to the pK„'s of the analogs (Table 2-30) and a 



Table 2-30 

 Inhibition of Yeast Alcohol Dehydrogenase by Substituted Pyridines" 



" From van Eys and Kaplan (1957 a). 



straight line is obtained by plotting pK^ against p^^. The pyridinium ions 

 are presumably the active inhibitors. The iV-methyl derivatives are rela- 

 tively weak inhibitors. The pyridine N must be important for the binding, 

 its properties being altered by the substituents (the stronger the electro- 

 negativity of the substituent, the greater the inhibition). It is thus evident 

 from these data that the pyridine analogs can inhibit various enzymes di- 

 rectly; it is likely that these effects are not as important as those arising 

 from the corresponding NAD analogs in whole animals. 



If the major actions of 3-acetylpyridine are mediated through 3-AcPyr- 

 NAD, the susceptibility of microorganisms or animals to 3-acetylpyridine 



