Model Reactions of NAD P H-Dependent Dehydrogenases

Within a molecule of NAD(P)H, the 1,4-dihydronicotinamide moiety acts as a reducing reagent. Thus, a 1,4-dihydropyridine derivative where the ring nitrogen is substituted by a simple substituent, such as 1-propyl-1,4-dihydronicotinamide (PNAH), 1-benzyl-1, 4-dihydro-nicotinamide (BNAH), or Hantzsch ester (HEH), can be considered as a model compound for NAD(P)H. 

Simulation of the reactions of dehydrogenases using 1, 4-dihydro-pyridine derivatives has been widely investigated (Eisner and Kuthan 1972, Stout and Meyers 1982). These compounds reduce C=0, C=C, C=N, and C=S double bonds as well as flavin and metal ions (Kill and Widdowson 1978, Okamoto et al. 1979). However, they are not so reactive toward the reduction compared with NAD(P)H in a biological system where an apoenzyme participates as a catalyst. The 1,4-dihydropyridine derivatives in a nonenzymatic system can reduce only those substrates like a,a,a-trifluoroacetophenone (TFA), hexachloro-acetone (HCA), and maleic anhydride(MA). That is, the substrate should be strongly electron-deficient in order to be reduced. 

Considering that the reactivity of the 1,4-dihydropyridine moiety extracted from the dehydrogenase system is very low, it is easily noticed that a specific field created by amino acid residues from the apoenzyme is very important for acceleration of the reaction. At the same time, it should be noted that such a reaction field at the active site of the enzyme contributes to the stereospecificity of the reaction. Although NAD(P)H contains chiral centers within the 

---