Stereospecificity, nicotinamide adenine

Dugan, R. E., Porter, J. W. Stereospecificity of the transfer of hydrogen from reduced nicotinamide adenine dinucleotide phosphate, in each of the two reductive steps catalyzed by /S-hydroxy-jS-methylglutaryl coenzyme A reductase. J. Biol. Chem. 246, 5361—5364 (1971). 

Davies, D. D., Teixeira, A., Kenworthy, P. The stereospecificity of nicotinamide-adenine dinucleotide-dependent oxido-reductases from plants. Biochem. J. 127, 335-343 (1972). 

In marked contrast, nature s reducing agent, reduced nicotinamide adenine dinucleotide (NADH), delivers hydride in a stereospecific manner because it is a cofactor in an enzyme-catalysed reaction. For example, reduction of pyruvic acid to lactic acid in vertebrate muscle occurs via attack of hydride to produce just one enantiomer, namely (5)-lactic acid. 

During the reduction sequence, NADH transfers a hydride from a prochiral centre on the dihydropyridine ring, and is itself oxidized to NAD+ (nicotinamide adenine dinucleotide) that contains a planar pyridinium ring. In the oxidation sequence, NAD+ is reduced to NADH by acquiring hydride to an enantiotopic face of the planar ring. The reactions are completely stereospecific. 

Functioning of the enzyme requires the presence of a coenzyme, nicotinamide adenine dinucleotide which exists in its oxidized (NAD+) or reduced (NADH) forms. The structure of NADH is shown in (177). Reduction or oxidation occurs by transfer of the pro-R C-4 hydrogen atom of the nicotinamide stereospecifically to or from the substrate. The reaction is therefore a ternary one, with the substrate and coenzyme necessarily within the active site for the reaction to occur.l46Sa... 

Byun, S.M., and Jenness, R., 1981, Stereospecificity of L-myo-inositol-1-phosphate synthase for nicotinamide adenine dinucleotide. Biochemistry 20 5174-5177. 

The 3-carbamidopyridinium ring is the chemically active portion of the enzymatic cofactors, NAD and NADP (nicotinamide adenine dinucleotide and its phosphate). A typical reaction involving NAD is the stereospecific (with respect to both cofactor and substrate) oxidation of ethanol to acetaldehyde catalyzed by the enzyme, alcohol dehydrogenase (Eq. 33). 

Jagodzinski PW, Peticolas WL (1981) Resonance enhanced Raman identification of the zinc-oxygen bond in a horse liver alcohol dehydrogenase-nicotinamide adenine dinucleotide-aldehyde transient chemical intermediate. J Am Chem Soc 103 234-236 Jakovac IJ, Goodbrand HB, Lok KP, Jones JB (1982) Enzymes in organic synthesis. 24. Preparations of enantiomerically pure chiral lactones via stereospecific horse liver alcohol dehydrogenase... 

Horse liver alcohol dehydrogenase (HLADH) catalyzes the oxidoreduction of a variety of compounds [61,62]. It has been demonstrated that HLADH catalyzes the stereospecific oxidation of only one of the enantiopic hydroxyl groups of acyclic and monocyclic me o-diols [63,64]. The oxidation of meso-exo- and enfto-7-oxabicyclo[2.2.1]heptane dimethanol to the corresponding enantiomerically pure y-lactones by HLADH has been demonstrated. Nicotinamide adenine dinucleotide (NAD" ) and flavin adenine dinucleotide (FAD) were required for the stereoselective oxidation of substrate. Due to the high cost of enzyme and required cofactors, this process for preparing chiral lactones was econom-... 

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