NAD P -linked enzymic oxidations

The two positions of position 4 of the reduced coenzyme NAD(P)H are diastereotopic, and NAD(P) -linked dehydrogenases are absolutely stereospecific for one or the other. The stereospecificity was denoted A or B, before there 

About 25 years ago, it was suggested that reaction stereospecificity was determined by reaction thermodynamics. Examination of the stereochemical outcomes of about 130NAD(P)-linked dehydrogenases led to the generalisation that if the equilibrium constant, defined by eqn. (6.3), is greater than 0.1 nM, B-side specificity is shown, whereas if it is less than 1 pM, A-side specificity results, and if it is in the 10 pM region, either specificity can be observed. 

In NAD solutions there is a 10-fold greater proportion of the syn conformation than in NADH. Therefore,. sjw-NAD is a weaker oxidising agent than awti-NAD. Hence, if the thermodynamic correlation holds, easier oxidations (higher ifeq) will have B-side stereochemistry. 

In addition to the stereospecilicity, NAD(P)H-linked dehydrogenases that convert CHOH to C=0 differ in the apparatus that has evolved to catalyse proton transfer from substrate oxygen. That apparatus can centre round a zinc ion or an acid-base histidine, tyrosine or lysine. 

The short-chain dehydrogenases, originally so called because the linear sequences then available rarely exceeded 250 residues, use tyrosine as the acid-base. As longer sequences with the same fold have become available, the name is something of a misnomer and the M,. range is now 250-350 residues for the core structure.They have B-side (proS) stereospecilicity for the coenzyme, which they bind in the syn conformation. Structurally, they adopt the same protein fold, much like a GH family, even though the degree of 

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