Stereospecificity for nicotinamide nucleotides in enzymatic and chemical hydride transfer reactions

Abstract

The pyridine nucleotide (NAD and NADP)-linked enzymes are a large class of enzymes constituting approximately 17% of all classified enzymes. When these enzymes catalyze their reactions, the hydride transfer between the substrate and the reaction site (i.e., C-4 of the nicotinamide/dihydronicotinamide ring) of the coenzyme takes place in a stereospecific manner. Thus, in the reaction of oxidation of the reduced coenzyme, one group of enzymes catalyzes the extraction of only the hydrogen having the R configuration at the No. 4 carbon, while the other group catalyzes the removal of only that with the S configuration. Because this aspect of enzyme stereospecificity provides essential information for a given enzyme's reaction mechanism, active site structure, and evolutionary relationship with other enzymes, intensive effort has been made to establish the stereospecificities of as many enzymes as possible. This review presents the compilation of the stereospecificities of these enzymes. Some empirical rules, which are useful but not definitive, in predicting a given enzyme's stereospecificity are also described. In addition, the stereospecificity in enzymatic reactions is compared to the stereo-preference in chemical oxidoreduction of the coenzyme. In order to elucidate the mechanism for the enzyme stereospecificity, the conformations of the coenzyme in free-state and enzyme-bound state are extensively discussed here.