NAD+ and NADP+ as Prosthetic Groups for Enzymes
Published Online: 19 APR 2010
Copyright © 2001 John Wiley & Sons, Ltd. All rights reserved.
How to Cite
Oppenheimer, N. J. 2010. NAD+ and NADP+ as Prosthetic Groups for Enzymes. eLS.
- Published Online: 19 APR 2010
NAD(P)+ (nicotinamide–adenine dinucleotide (phosphate)) serves as a coenzyme for pyridine nucleotide-dependent dehydrogenase catalysed redox reactions. When the coenzyme behaves as a nondissociable prosthetic group it can function to promote aldehyde dismutation with nicotinoproteins as well as regular alcohol dehydrogenases. The tightly bound coenzyme can also be used to conduct reversible redox reactions to catalyse epimerization of sugar hydroxyls and to trigger elimination reactions; for example, nucleotidyl diphosphohexose-4,6-dehydratases, ornithine cyclodeaminase and S-adenosyl-l-homocysteine hydrolase. Finally in urocanase the nicotinamide ring can participate directly as a Lewis acid to catalyse a complex rearrangement reaction. An important feature of these reactions is that because the coenzyme does not dissociate that they are independent of the NAD+/NADH (reduced form of nicotinamide–adenine dinucleotide) ratio of the cell.
In the standard spectrophotometric assay of dehydrogenases coenzyme release is rate limiting, but when the coenzyme cannot or does not dissociate then chemistry becomes limiting and reaction rates can be much faster when substrates are present for both forward and reverse reactions.
Dismutation of aldehydes and reactions catalysed by nicotinoproteins can occur without any change in the concentration of exogenous NADH, that is, no spectrophotometric change hence they are difficult to observe and assay.
For enzymes with tightly bound coenzyme, their reactions are not directly influenced by changes in the ratio of NAD+/NADH in the cell.
With the exception of nicotinoproteins, enzymes with nondissociable NAD+ can be inactivated by its reduction to NADH in the absence of the normal substrate, that is, there is no independent means of exchanging out the bound NADH or oxidizing it.
In spite of the chiral nature of their active sites epimerases catalyse an overall nonstereospecific reaction. Although the hydride transfer reaction retains its exquisite stereochemical fidelity the binding of the substrate has greatly decreased stringency allowing reactions with either epimer, hence eventually leading to the thermodynamically favoured mixture.
In addition to redox reactions the catalytic machinery of dehydrogenases can promote a wide range of other chemistry including dehydrations and rearrangements provided the substrate can be properly activated and bound in the appropriate juxtaposition to the coenzyme.
The pyridinium ring of NAD+ can serve as a Lewis acid for reactions where protonation does not provide the correct pathway.