Nicotinamide, donor-acceptor

Nicotinamide adenine dinucleotide (NAD+ and NADP+) is the biochemical hydride donor/acceptor [2]. 

In Fig. 9 we show the results of a 30-ps simulation for the donor-acceptor distance, i.e. the distance between the C2 carbon of substrate and carbon C4N of the nicotinamide ring of the cofactor NAD + /NADH. Fig. 9 shows that the average donor-acceptor distance is shorter for the heart isoform when lactate and NAD + are bound, and for the muscle isoform when pyruvate and NADH are bound. We propose that the different kinetic activity of the two isoforms is due to the reduced donor-acceptor distance when lactate is bound to the heart isoform and pyruvate is bound to the muscle isoform. 

Nicotinamide is an essential part of two important coenzymes nicotinamide adenine dinucleotide (NAD ) and nicotinamide adenine dinucleotide phosphate (NADP ) (Figure 18.19). The reduced forms of these coenzymes are NADH and NADPH. The nieotinamide eoenzymes (also known as pyridine nucleotides) are electron carriers. They play vital roles in a variety of enzyme-catalyzed oxidation-reduction reactions. (NAD is an electron acceptor in oxidative (catabolic) pathways and NADPH is an electron donor in reductive (biosynthetic) pathways.) These reactions involve direct transfer of hydride anion either to NAD(P) or from NAD(P)H. The enzymes that facilitate such... 

The most important coenzymes in synthetic organic chemistry [14] and industrially applied biotransformations [15] are the nicotinamide cofactors NAD/ H (3a/8a, Scheme 43.1) and NAD(P)/H (3b/8b, Scheme 43.1). These pyridine nucleotides are essential components of the cell [16]. In all the reactions where they are involved, they serve solely as hydride donors or acceptors. The oxidized and reduced form of the molecules are shown in Scheme 43.1, the redox reaction taking place at the C-4 atom of the nicotinamide moiety. 

Nicotinic acid derivatives occur in biologic materials as the free acid, as nicotinamide, and in two coenzymatic forms nicotinamide adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide phosphate (NADP). These coenzymes act in series with flavoprotein enzymes and, like them, are hydrogen acceptors or, when reduced, donors. Several plants and bacteria use a metabolic pathway for the formation of nicotinic acid that is different from the tryptophan pathway used by animals and man (B39). 

Two important implications of the reactions described in Equations (5.1) and (5.2) are (i) that redox reactions play an important role in metabolic transformations, with the cofactors nicotinamide adenine dinucleotide (NAD+) acting as electron acceptor in catabolic pathways and nicotinamide adenine dinucleotide phosphate (NADPH) as electron donor in anabolism, and (ii) that energy must be produced by catabolism and used in biosyntheses (almost always in the form of adenosine triphosphate, ATP). 

Two vitamins, nicotinamide and pyridoxine (vitamin B6), are pyridine derivatives. Nicotinamide participates in two coenzymes, coenzyme I (65 R = H) which is known variously as nicotinamide adenine dinucleotide (NAD) or diphosphopyridine nucleotide (DPN), and coenzyme II (65 R = P03H2) also called triphosphopyridine nucleotide (TPN) or nicotinamide adenine dinucleotide phosphate (NADP). These are involved in many oxidation-reduction processes, the quaternized pyridine system acting as a hydrogen acceptor and hydrogen donor. Deficiency of nicotinamide causes pellagra, a disease associated with an inadequately supplemented maize diet. Nicotinic acid (niacin) and its amide are... 

I. 1-anthryl-l -naphthyl alkanes. II. Nicotinamide-adenine-dinucleotide (reduced) NADH. IFF Oligomers of poly-L-proline with a-naphthyl group as energy donor and dansyl group as energy acceptor. III. p-methoxy benzene and flourene chromophere in norbornadiene-spirocyio-propane frame. V and VI. Anthrone and naphthalene chromphore in spiro-compounds. 

Since many of the transformations undergone by metabolites involve changes in oxidation state, it is understandable that cofactors have been developed to act as electron acceptors/donors. Two of the most important are NAD and NADP (Figure 5.2). Nicotinamide adenine dinucleotide (NAD ) can accept what is essentially two electrons and a proton (a hydride ion) from a substrate like ethanol in a reaction catalysed by alcohol dehydrogenase, to give the oxidised product, acetaldehyde, and the reduced cofactor NADH plus a proton ... 

The two-domain, structural motif in FNR represents a common structural feature in a large class of enzymes that catalyze electron transfer between a nicotinamide dinucleotide molecule and a one-electron carrier. Beside the photosynthetic electron-transfer enzyme, others non-photosynthetic ones include flavodoxin reductase, sulfite reductase, nitrate reductase, cytochrome reductase, and NADPH-cyto-chrome P450 reductase. FNR belongs to the group of so-called dehydrogenases-electron transferases, i.e., flavoproteins that catalyze electron transfer from two, one-electron donor molecules to a single two-electron acceptor molecule. 

The answer is b. (Murray, pp 627-661. Scriver, pp 3897-3964. Sack, pp 121-138. Wilson, pp 287-320.) Nicotinamide adenine dinucleotide (NAD+) is the functional coenzyme derivative of niacin. It is the major electron acceptor in the oxidation of molecules, generating NADH, which is the major electron donor for reduction reactions. Thiamine (also known as vitamin Bi) occurs functionally as thiamine pyrophosphate and is a coenzyme for enzymes such as pyruvate dehydrogenase. Riboflavin (vitamin B2) functions in the coenzyme forms of flavin mononucleotide (FMN) or flavin adenine dinucleotide (FAD). When concentrated, both have a yellow color due to the riboflavin they contain. Both function as prosthetic groups of oxidation-reduction enzymes or flavoproteins. Flavoproteins are active in selected oxidation reactions and in electron transport, but they do not have the ubiquitous role of NAD+. 

In the third configuration MC, we have NAD+ and PhCH20- with the pro-R hydrogen restrained so that it is equidistant from the hydroxyl a-carbon (hydride donor) and the C4 carbon (hydride acceptor) in the nicotinamide ring. 

Coenzymes provide chemical functional groups that proteins lack. For example, only sulfhydryl groups on amino acids are able to participate in oxidation and reduction reactions, and the formation/breakage of disulfides does not provide enough reducing power to alter most biomolecules s functional groups. Electron transfer requires one of several coenzymes, usually either nicotinamide adenine dinucleotide, NAD, or flavin adenine dinucleotide, FAD, as electron acceptors and donors. Table 7-1 shows some of these coenzymes. 

Aakeroy and co-workers and Nangia and co-workers were successful in the exploitation of Etter s hydrogen bonding hierarchy rule to design binary and ternary complexes of nicotinamide (2) and iso-nicotinamide (3) with carboxylic acids and phenols [14]. Synthon I was retained in iso-nicotinamide co-crystals with succinic acid and 3-hydroxybenzoic acid (Figure 7.6) [14d]. In these structures the carboxylic acid interacts, as a strong proton donor, with a strong proton acceptor such as pyridine. 

The redox reaction occurs specifically at the nicotinamide part of the molecule. The NAD+ and NADP+ forms act as hydride acceptors (oxidizing agents), whereas the reduced forms NADH and NADPH serve as hydride donors (reducing agents). 

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