Nicotinamide adenine dinucleotide transformation

For the majority of redox enzymes, nicotinamide adenine dinucleotide [NAD(H)j and its respective phosphate [NADP(H)] are required. These cofactors are prohibitively expensive if used in stoichiometric amounts. Since it is only the oxidation state of the cofactor that changes during the reaction, it may be regenerated in situ by using a second redox reaction to allow it to re-enter the reaction cycle. Usually in the heterotrophic organism-catalyzed reduction, formate, glucose, and simple alcohols such as ethanol and 2-propanol are used to transform the... 

The asymmetric reduction of prochiral functional groups is an extremely useful transformation in organic synthesis. There is an important difference between isolated enzyme-catalyzed reduction reactions and whole cell-catalyzed transformations in terms of the recycling of the essential nicotinamide adenine dinucleotide (phosphate) [NAD(P)H] cofactor. For isolated enzyme-catalyzed reductions, a cofactor recycling system must be introduced to allow the addition of only a catalytic amount (5% mol) of NAD(P)H. For whole cell-catalyzed reductions, cofactor recycling is automatically achieved by the cell, and the addition of a cofactor to the reaction system is normally not required. 

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). 

Most coenzymes have aromatic heterocycles as major constituents. While enzymes possess purely protein structures, coenzymes incorporate non-amino acid moieties, most of them aromatic nitrogen het-erocycles. Coenzymes are essential for the redox biochemical transformations, e.g., nicotinamide adenine dinucleotide (NAD, 13) and flavin adenine dinucleotide (FAD, 14) (Scheme 5). Both are hydrogen transporters through their tautomeric forms that allow hydrogen uptake at the termini of the quinon-oid chain. Thiamine pyrophosphate (15) is a coenzyme that assists the decarboxylation of pyruvic acid, a very important biologic reaction (Scheme 6). 

Note how the above reactions are written. It s common when writii biochemical transformations to show only the structures of the reactant and product, whUe abbreviating the structures of coenzymes and other reactants. The curved arrow intersecting the usual strsiight reaction arrow io the first step shows that ATP is also a reactant and that ADP is a product. The coenzyme nicotinamide adenine dinucleotide (NAD ) is required in the second step, and reduced nicotinamide adenine dinucleotide (NADH) plus a proton are products. We ll see shortly that NAD is often involved as a biochemical oxidizing agent for converting alcohols to ketones or aldehydes. 

NAD+ Oxidized form of nicotinamide adenine dinucleotide. Note that despite the plus sign in the symbol, the coenzyme is anionic under normal physiological conditions. NAD+ is a coenzyme derived from the B vitamin niacin. It is transformed into NADH when it accepts a pair of high-energy electrons for transport in cells and is associated with catabolic and energy-yielding reactions. 

Two important implications of the reactions described in Equations (1) and (2) are (i) that redox reactions play an important role in metabolic transformations, with the cofactors nicotinamide adenine dinucleotide (NAD )... 

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 first step in XJVR-induced skin cancer is UVR-initiated DNA mutation, which causes the transformation of the normal cells to malignant cells. For UVR to initiate a biological reaction, it has to be absorbed by endogenous molecules (chromophores). UVB is absorbed directly by the DNA, and therefore can directly induce DNA mutation (224), in the form of thymine dimer formation (289). Some protein components may also ad as chromophores for UVB (224). UVA is absorbed by the reduced forms of the co-enzymes nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), tryptophan, riboflavin, and melanin (224,290). UVA-induced DNA damage is believed to be mediated by oxygen reactive species that are released after the absorption of UVA by those endogenous chromophores and results in photooxidation of selected bases... 

In vitro metabolic studies with rodent and human liver microsomal prepara- tions have established that MPTP undergoes both oxidative N-demethylation and C-6 (allylic) oxidation in reactions that are -nicotinamide adenine dinucleotide phosphate (NADPH) dependent and therefore likely to be cytochrome P-450 catalyzed (Weissman et al. 1985 Ottoboni et al. 1990). Although the latter transformation can lead to the toxic pyridinium metabolite MPP, the cytochrome P450-catalyzed pathway is unlikely to contribute significantly to the neurotoxicity of MPTP. As mentioned above, liver aldehyde oxidase diverts the inter-mediate dihydropyridinium metabolite away from pyridinium ion formation by catalyzing the conversion of structure 40 to the nontoxic lactim structure 41. Further-more, even if formed in the periphery, the polar pyridinium metabolite would have limited access to the central nervous system (CNS). The low... 

Electron-transfer (ET) reactions play a central role in all biological systems ranging from energy conversion processes (e.g., photosynthesis and respiration) to the wide diversity of chemical transformations catalyzed by different enzymes (1). In the former, cascades of electron transport take place in the cells where multicentered macromolecules are found, often residing in membranes. The active centers of these proteins often contain transition metal ions [e.g., iron, molybdenum, manganese, and copper ions] or cofactors as nicotinamide adenine dinucleotide (NAD) and flavins. The question of evolutionary selection of specific structural elements in proteins performing ET processes is still a topic of considerable interest and discussion. Moreover, one key question is whether such stmctural elements are simply of physical nature (e.g., separation distance between redox partners) or of chemical nature (i.e., providing ET pathways that may enhance or reduce reaction rates). 

Figure 7.70 Structures of resazurin and resorufin. The transformation from blue resazurin to red fluorescing resorufin by reduction is catalysed by the redox reaction of nicotinamide adenine dinucleotide (NAD+, coenzyme 1) to NAD dehydrogenase.

Figure 2 NAD biosynthesis subsystem diagram. Major functional roles are shown by 4-6 letter abbreviations (explained in Table 1) over the colored background reflecting the key aspects or modules (pathways) that comprise NAD biosynthesis in various species. Catalyzed reactions are shown by solid straight arrows, and corresponding intermediate metabolites are shown as abbreviations within ovals Asp, L-aspartate lA, Iminoaspartate Qa, quinolinic acid Nm, nicotinamide Na, nicotinic acid NaMN, nicotinic acid mononucleotide NMN, nicotinamide mononucleotide RNm, N-ribosyInicotinamide NaAD, nicotinate adenine dinucleotide NAD, nicotinamide adenine dinucleotide NADP, NAD-phosphate Trp, tryptophan FKyn, N-formylkynurenine Kyn, kynurenine HKyn, 3-hydroxykynurenine HAnt, 3-hydroxyanthranilate and ACMS, a-amino-/3-carboxymuconic semialdehyde. Unspecified reactions (including spontaneous transformation and transport) are shown by dashed arrows.

In E. coli, ThiH catalyzes the formation of the glycine imine 23 from tyrosine (26). ThiH is an oxygen-sensitive radical 5-adenosyl-L-methionine (SAM) enzyme. Its activity has been reconstituted and the mechanism outlined in Figure 8 has been proposed. It is unclear why E. coli adopts such a complex route to the glycine imine when oxidation of glycine using nicotinamide adenine dinucleotide (NAD) would accomplish the same transformation. 

Electrochemical transformations of nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) have been dealt with in several publications, since they are the most important hydrogen carriers. There are reviews on this topic/" The standard redox potential of the NAD(P)H/NAD(P) couple has been found to be —0.32... 

Rgure 2 Structural formulae of two enzyme cofactors (A) nicotinamide adenine dinucleotide (NAD) and (B) flavin adenine dinucleotide (FAD) with the corresponding redox transformations in dehydrogenases and oxidases catalyzed reaction, respectively. NAD is a soluble cofactor and it has to be added to the reaction mixture. As shown in Figure 1, FAD is bound to the flavoprotein. 

Nature makes use of NADH (reduced nicotinamide adenine dinucleotide) as a cofactor for enantioselective biochemical hydrogenations, which are typical hydride-transfer reactions. Dihydropyridines and benzimidazolines derivatives are active hydride donors due to the presence of the nitrogen atom and the ability of the molecule to undergo aromatisation. Organocatalytic enantioselective reductions carried out using hydride donors has been studied, and effective reductions have been achieved with imidazoli-dinone organocatalysts, both with a,p unsaturated aldehydes and ketones. Generally, a stoichiometric quantity of reductant (Hantzsch ester 4) is required for these transformations (Scheme 18.5). 

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