NAD+ and NADP

Nicotinamide and nicotinic acid occur in nature almost exclusively in the bound form. In plants, nicotinic acid is prevalent whereas in animals nicotinamide is the predominant form. This nicotinamide is exclusively in the form of NAD and NADP. 

NAD and NADP are required as redox coen2ymes by a large number of enzymes and ia particular dehydrogenases (Fig. 6). NAD" is utilized ia the catabohe oxidations of carbohydrates, proteins, and fats, whereas NADPH2 is the coenzyme for anaboHc reactions and is used ia fats and steroid biosynthesis. NADP+ is also used ia the cataboHsm of carbohydrates (2). 

FIGURE 18.20 NAD and NADP participate exclusively iii two-electroii transfer reactions. For example, alcohols can be oxidized to ketones or aldehydes via hydride transfer to NAD(P). ... 

The NAD- and NADP-dependent dehydrogenases catalyze at least six different types of reactions simple hydride transfer, deamination of an amino acid to form an a-keto acid, oxidation of /3-hydroxy acids followed by decarboxylation of the /3-keto acid intermediate, oxidation of aldehydes, reduction of isolated double bonds, and the oxidation of carbon-nitrogen bonds (as with dihydrofolate reductase). 

Access to three different redox states allows flavin coenzymes to participate in one-electron transfer and two-electron transfer reactions. Partly because of this, flavoproteins catalyze many different reactions in biological systems and work together with many different electron acceptors and donors. These include two-electron acceptor/donors, such as NAD and NADP, one- or two-elec-... 

Nicotinamide and nicotinic acid are both white crystalline substances. Their aqueous solution has a maximal UV absorbance at 263 nm. Both vitamers have the same biological activity as they can be converted into each other. Figure 2 shows the structure of the coenzyme forms NAD+ and NADP+. 

NAD+ and NADP+ are coenzymes of dehydrogenases. NADH and NADPH are intermediate carriers of both hydrogen and electrons. Most NAD-dependent enzymes are located in the mitochondria and deliver H2 to the respiratory chain whereas NADP-dependent enzymes take part in cytosolic syntheses (reductive biosyntheses). 

NAD and NADP and FMN and FAD, respectively. Pantothenic acid is a component of the acyl group carrier coenzyme A. As its pyrophosphate, thiamin participates in decarboxylation of a-keto acids and folic acid and cobamide coenzymes function in one-carbon metabolism. 

Niacin Nicotinic acid, nicotinamide Coenzyme in oxidation and reduction reactions, functional part of NAD and NADP Pellagra—photosensitive dermatitis, depressive psychosis... 

Niacin was discovered as a nutrient during studies of pellagra. It is not strictly a vitamin since it can be synthesized in the body from the essential amino acid tryptophan. Two compounds, nicotinic acid and nicotinamide, have the biologic activity of niacin its metabolic function is as the nicotinamide ring of the coenzymes NAD and NADP in oxidation-reduction reactions (Figure 45-11). About 60 mg of tryptophan is equivalent to 1 mg of dietary niacin. The niacin content of foods is expressed as mg niacin equivalents = mg preformed niacin + 1/60 X mg tryptophan. Because most of the niacin in cereals is biologically unavailable, this is discounted. 

Complex 9 (Scheme 43.3) can be reduced by different redox equivalents to the active rhodium(I) species 10 namely, by electrons, formate [37, 38], and hydrogen. This hydrido complex then transfers the hydride ion onto the nicotinamide. In electrochemical applications, TOFs in the range of 5 to 11 h-1 have been reported [31, 39]. It is noteworthy that this complex accepts NAD+ and NADP+ as substrates with the same efficiency and almost exclusively produces the 1,4-reduced cofactor (selectivity >99%). 

Until now, only a few versatile, selective and effective transition-metal complexes have been applied in nicotinamide cofactor reduction. The TOFs are well within the same order of magnitude for all systems studied, and are within the same range as reported for the hydrogenase enzyme thus, the catalytic efficiency is comparable. The most versatile complex Cp Rh(bpy) (9) stands out due to its acceptance of NAD+ and NADP+, acceptance of various redox equivalents (formate, hydrogen and electrons), and its high selectivity towards enzymatically active 1,4-NAD(P)H. 

The antagonists of nicotinic acid are 6-aminonicotinamide and, less potent, 3-acetylpyridine and pyridine-3-sulfonic acid (H15, J4). Nicotinamide has also been reported to be effective in experimental cancer (S3). It is supposedly converted to nonphysiological nucleotide analogs of NAD and NADP because it becomes attached to available apo-dehydrogenase the resulting enzyme cannot function in hydrogen and electron-transfer reactions essential to normal cellular metabolism (D7). 

In accordance with the recommendation of the Commission of the International Union of Biochemistry [R. H. S. Thompson, Classification and nomenclature of enzymes and coenzymes, Nature 193, 1227 (1902)] the terms NAD and NADP have been used instead of DPN and TPN, except in Fig. 4. The generic term nicotinamide nucleotides is used with the same significance as pyridine nucleotides. 

Figure 5.2 The structure of NAD+ and NADP+ and the role of the nicotinamide moiety as an...

The natural substrates which are most frequently used are the nucleotide coenzymes NAD+ and NADP+, which are reversibly reduced by many enzymes ... 

Note All NAD+- and NADP - linked enzyme assays are also capable of being monitored fluorimetrically. The fluorescent compounds in each assay are shown in bold type. ... 

Those nucleosides found in the nucleic acids DNA and RNA involve the joining of ribose of deoxyribose to a purine or a pyrimidine base. One such nucleoside is adenosine, in which a nitrogen of adenine is linked to carbon 1 of the pentose, ribose. In this form it is a component of RNA but as a phosphory-lated derivative of adenosine (e.g. ATP), which is a high energy compound, it fulfils an important role in metabolism. The dinucleotides NAD and NADP are two cofactors necessary for many enzymic transformations and these also contain /V-glycosides of ribose phosphate. Other important nucleosides are found... 

When an enzyme reacts with both pyridine nucleotides, NAD and NADP, it has the same stereospecificity for each of them. We can probably add to NAD and NADP, the analogues of either 88>. 

Alcohols have been converted into aldehydes mediated by a lipophilic / -cyclodextrin bearing a ferrocene moiety [139]. Efficient indirect in situ electroregeneration of NAD+ and NADP+ for enzymatic oxidations of butanol and 2-hexen-l-ol leading to the corresponding aldehydes using Fe bipyridine and phenanthroline complexes as redox... 

Biocatalytic approaches to cofactor regeneration can be divided into coupled-enzyme methods and coupled-substrate methods.In the coupled-enzyme method, the oxidized cofactors (NAD+ and NADP+) are recycled in situ by performing an oxidation reaction using a second enzyme and an inexpensive auxiliary substrate. This second enzyme must employ the same cofactor, but neither enzyme should be able to accept the same substrate. 

Electron carriers Biomolecules, such as NAD and NADP that act to transport energy within cells... 

Niacin the generic name for nicotinic acid and nicotinamide precursors for the coenzymes NAD+ and NADP+. 

Nicotinic acid and nicotinamide are precursors of the coenzymes NAD+ and NADP+, which play a vital role in oxidation-reduction reactions (see Box 7.6), and are the most important electron carriers in intermediary metabolism (see Section 15.1.1). We shall look further at the chemistry of NAD+ and NADP+ shortly (see Box 11.2), but note that, in these compounds, nicotinamide is bound to the rest of the molecule as an A-pyridinium salt. 

The substrate in most reactions of this type is an alcohol, which becomes oxidized to an aldehyde or ketone, e.g. ethanol is oxidized to acetaldehyde. Some reactions employ the alternative phosphorylated cofactor NADP+ the phosphate does not function in the oxidation step, but is merely a recognition feature helping to bind the compound to the enzyme. The full structures of NAD+ and NADP+ are shown in Box 11.1. 

FAD shares a lot of features with NAD+ and NADP+, but contains two new variants a sugar that is neither ribose nor deoxyribose, and a fairly complex heterocyclic base flavin. The new sugar is ribitol, non-cyclic because it contains no carbonyl group (see Section 12.3). The chemistry of FAD is concentrated in the flavin part, and features oxidation/reduction processes (see Box 11.14). 

The pyridine nucleotides NAD and NADP always function in unbound form. The oxidized forms contain an aromatic nicotinamide ring in which the positive charge is delocalized. The right-hand example of the two resonance structures shown contains an electron-poor, positively charged C atom at the para position to nitrogen. If a hydride ion is added at this point (see above), the reduced forms NADH or NADPH arise. No radical intermediate steps occur. Because a proton is released at the same time, the reduced pyridine nucleotide coenzymes are correctly expressed as NAD(P)H+HT... 

The pyridine nucleotides NAD"" and NADP" (1) are widely distributed as coenzymes of dehydrogenases. They transport hydride ions (2e and 1 see p. 32) and always act in soluble form. NAD" transfers reducing equivalents from catabolic pathways to the respiratory chain and thus contributes to energy... 

Hydride Transfer in NAD+- and NADP -Dependent Enzymes. The transfer of the hydride ion in redox reaction of NAD+- and NADP+-dependent enzymes can occur either to the re- or the xi-face of the pyridine ring of the coenzyme . Such stereochemistry is crucial in the characterization of these enzymes. The same enzymes from different sources can express different stereospecificities. For example, E. coli NAD(P)+ transhydrogenase expressed one form of stereospecificity whereas the Pseudomonas aeruginosa enzyme catalyzes the identical reaction with the other NAD form . 

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