ANALOGS OF NICOTINAMIDE 



507 



kinase and malate dehydrogenase). However, NADP is additionaUy phos- 

 phorylated in the 2-position and, as has been especially emphasized by 

 Neufeld et al. (1955), enzymes reacting with NADP are frequently inhibited 

 by 2'-AMP. In addition to the enzymes listed in Table 2-31 (NADPH dia- 

 phorase, NADP-cytochrome c reductase, glucose-6-P dehydrogenase, and 

 isocitrate dehydrogenase), they found phosphogluconate dehydrogenase and 

 NADP-activated oxalacetate decarboxylase to be inhibited by 2'-AMP more 

 than by the other AMP's. It was suggested that 2'-AMP may be a useful 

 inhibitor to distinguish between NAD and NADP enzymes. It must be 

 admitted that an insufficient number of NAD enzymes have been examined. 

 It is interesting that the NAD : NADP transhydrogenase is inhibited more 

 potently by 2'-AMP than by 3'- and 5'-AMP. 



100 



Fig. 2-17. Inhibitions of glutamate semialdehyde reductase by various nucleosides 

 and nucleotides. (From Smith and Greenberg, 1957.) 



The importance of phosphate groups for the binding of inhibitors of this 

 type is seen strikingly in the study on glutamic semialdehyde reductase by 

 Smith and Greenberg (1957) (Fig. 2-17). The inhibitions by AMP, ADP, 

 and ATP are competitive, but NADP inhibits noncompetitively. Although 

 the addition of the first phosphate to form AMP has little effect (not more 

 than 0.1 kcal/mole), the addition of each of the next two phosphates to 



