Redox nicotinamide adenine dinucleotide

Oxidation of P-nicotinamide adenine dinucleotide (NADH) to NAD+ has attracted much interest from the viewpoint of its role in biosensors reactions. It has been reported that several quinone derivatives and polymerized redox dyes, such as phenoxazine and phenothiazine derivatives, possess catalytic activities for the oxidation of NADH and have been used for dehydrogenase biosensors development [1, 2]. Flavins (contain in chemical structure isoalloxazine ring) are the prosthetic groups responsible for NAD+/NADH conversion in the active sites of some dehydrogenase enzymes. Upon the electropolymerization of flavin derivatives, the effective catalysts of NAD+/NADH regeneration, which mimic the NADH-dehydrogenase activity, would be synthesized [3]. 

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... 

It is well known that the selective transport of ions through a mitochondrial inner membrane is attained when the oxygen supplied by the respiration oxidizes glycolysis products in mitochondria with the aid of such substances as flavin mononucleotide (FMN), fi-nicotinamide adenine dinucleotide (NADH), and quinone (Q) derivatives [1-3]. The energy that enables ion transport has been attributed to that supplied by electron transport through the membrane due to a redox reaction occurring at the aqueous-membrane interface accompanied by respiration [1-5],... 

The biological applications of tetrazolium salts are the subject of a textbook.96 Kuhn and Jerchel74 were the first to recognize the utility of tetrazolium salts as indicators in redox enzyme activity, particularly those of the various dehydrogenases. It has been recognized449 that this particular utility of tetrazolium salts is related to the proximity of their redox potentials to those of the hydride transfer systems in biology450 such as nicotinamide adenine dinucleotide, NAD, and its phosphate analogue, NADP. 

Dehydrogenases, which represent a majority of redox enzymes, are mostly NAD (Nicotinamide Adenine Dinucleotide, see Fig. 12.9) dependent. This cofactor is not directly bound to the enzyme but its presence in the medium is necessary because it acts as a carrier of two electrons and one proton, and it activates the biocatalytic function of the enzyme. 

Anaerobic azo dye reduction can be mediated by enzymes, low molecular weight redox mediators, and chemical reduction by biogenic reductants. These reactions can be located either intracellular or extracellular. Reduction of highly polar azo dyes, which cannot pass through the cell membranes, is located outside the cell. Like azo dyes, nicotinamide adenine dinucleotide phosphate, which is believed to be the main source of electrons, also cannot pass through the cell membranes. Azo reductase enzyme, which is oxygen-sensitive and released extracellularly, is found to be responsible for the reduction of azo dyes. 

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). 

By means of this reaction, the use of the costly and unstable natural redox cofactor reduced nicotinamide adenine dinucleotide phosphate (NADPH) was circumvented and the reactions were carried out in a straightforward procedure in a chemical laboratory (Scheme 10.2, Table 10.1). 

In view of the oxidant nature of ozone, a number of investigators have evaluated its effects on intracellular compounds that are normally active in cellular redox reactions. Attention has focused particularly on reduced pyridine nucleotides—reduced nicotinamide adenine dinudeotide (NADH) and reduced nicotinamide adenine dinucleotide phosphate (NADPH)— and on sulfhydryl compounds, specifically reduced glutathione (GSH). 

NAD(P)+ as Anode Mediator. A majority of redox enzymes require the cation nicotinamide adenine dinucleotide, possibly phosphorylated (NAD(P)+) as a cofactor. Of the oxidoreductases listed in Enzyme Nomenclature, over 60% have NAD(P)+ as a reactant or product.For example, methanol can be oxidized to form formaldehyde by methanol dehydrogenase (MDH, EC 1.1.1.244) according to... 

Although the structures for molecules having niacin activity are simple, the forms in which they act in human biochemistry are not so simple. Nicotinic acid and nicotinamide are precursors for three complex coenzymes in multiple oxida-tion/reduction (redox) reactions nicotinamide mononucleotide, NMN nicotinamide adenine dinucleotide, NAD+ and nicotinamide adenine dinucleotide phosphate, NADP. I shall use NAD+ as representative of the class. NADH is the corresponding reduced form. ... 

Niacin is also known as vitamin PP or vitamin Bj. The term niacin describes two related compounds, nicotinic acid and nicotinamide (Figure 19.18), both with biological activity. Niacin is formed from the metabolism of tryptophan, and therefore it is not strictly a vitamin. It is a precursor of two cofactors nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are essential for the functioning of a wide range of enzymes involved in redox reactions. 

Boron also appears to be involved in redox metabolism in cell membranes. Boron deficiency was shown to inhibit membrane H -ATPase isolated from plant roots, and H -ATPase-associated proton secretion is decreased in boron-deficient cell cultures [71]. Other studies show an effect of boron on membrane electron transport reactions and the stimulation of plasma reduced nicotinamide adenine dinucleotide (NADH) oxidase upon addition of boron to cell cultures [72, 73]. NADH oxidase in plasma membrane is believed to play a role in the reduction of ascorbate free radical to ascorbate [74]. One theory proposes that, by stimulating NADH oxidase to keep ascorbate reduced at the cell wall-membrane interface, the presence of boron is important in... 

Although zinc itself is not redox-active, some class I enzymes containing zinc in their active sites are known. The most prominent are probably alcohol dehydrogenase and copper-zinc superoxide dismutase (Cu,Zn-SOD). AU have in common that the redox-active agent is another transition-metal ion (copper in Cu,Zn-SOD) or a cofactor such as nicotinamide adenine dinucleotide (NAD+/NADH). The Zn(II) ion affects the redox reaction only in an indirect manner, but is nevCTtheless essential and cannot be regarded simply as a structural factor. 

Two derivatives of nicotinamide (pyridine-3-carboxylic amide), one of the B2 vitamins, nicotinamide adenine dinucleotide (NAD ) and nicotinamide adenine dinucleotide phosphate (NADP ), serve as redox coenzymes. Of the three heterocyclic ring systems found in these coenzymes, i.e. those of purine, ribose and pyridine, it is the pyridine portion that is reactive in redox reactions. Biologically, two oxidation states are important the oxidized form, NAD(P)+, and the 1,4-dihydro isomer of the two-electron reduced form, NAD(P)H (Scheme 1). Nicotinamide coenzymes interconvert between these two oxidation states in... 

Several of the B vitamins function as coenzymes or as precursors of coenzymes some of these have been mentioned previously. Nicotinamide adenine dinucleotide (NAD) which, in conjunction with the enzyme alcohol dehydrogenase, oxidizes ethanol to ethanal (Section 15-6C), also is the oxidant in the citric acid cycle (Section 20-10B). The precursor to NAD is the B vitamin, niacin or nicotinic acid (Section 23-2). Riboflavin (vitamin B2) is a precursor of flavin adenine nucleotide FAD, a coenzyme in redox processes rather like NAD (Section 15-6C). Another example of a coenzyme is pyri-doxal (vitamin B6), mentioned in connection with the deamination and decarboxylation of amino acids (Section 25-5C). Yet another is coenzyme A (CoASH), which is essential for metabolism and biosynthesis (Sections 18-8F, 20-10B, and 30-5A). 

Another important set of reactions in living systems comprise those that involve redox processes. Reduced pyridine nucleotides, nicotinamide adenine dinucleotide... 

NAD) and nicotinamide adenine dinucleotide phosphate (NADP), are the universal carriers of hydrogen and electrons, or metabolic reducing power. Many redox processes may be linked together in electron transport chains. 

C.O. Schmakel, K.S.V. Santhanam and P.J. Elving, Nicotinamide adenine dinucleotide (NAD+) and related compounds. Electrochemical redox pattern and allied chemical behavior, J. Am. Chem. Soc., 97(18) (1975) 5083-5092. 

Several reactions in metabolism are oxidation-reduction (or redox) reactions. Two of the principal redox carriers are nicotinamide adenine dinucleotide (NAD+) and coenzyme Q. Remember that we live in an oxidizing world, so species that are in the reduced form are frequently high-energy compounds that react exothermically with oxygen. Also recall that organic molecules are reduced by adding bonds to hydrogen. 

Chemically modified electrodes (CMEs) for electrocatalytic oxidation of the reduced form of the nicotinamide adenine dinucleotide cofactor (NADH) are discussed. The work of the authors in the field is reviewed. CMEs based on adsorbed polyaromatic redox mediators (phenoxazines and phenothiazines) and the deposition of aqueous insoluble redox polymers are described. 

When the dehydrogenases are used in analysis the method relies on measuring the change in the redox state of the cofactor, i.e. the change in the concentration of NAD or NADH. NADH is inherently more easily detected photometrically and electrochemically (see below) than its oxidized counterpart, NAD+ 13). When catalyzed by a dehydrogenase, the redox reaction of the nicotinamide adenine dinucleotides (NAD(P)+/NAD(P)H) is reversible, see Figure 1. A reaction catalyzed by a dehydrogenase can be schematically written as follows ... 

Figure 1. Structural formulae (/3-form shown) and overall redox reaction of nicotinamide adenine dinucleotide, NAD+, and its reduced form, the enzymatically active 1,4-NADH. Reproduced with permission from ref. 35. Copyright 1991 Elsevier Science Publishers.

Both competing reductions consume the cofactor nicotinamide adenine dinucleotide (NADH) and thereby interfere with the redox balance of the cell and feedback on glycolysis where NADH is regenerated on the one hand, while on the other hand NAD+ is required to keep the glycolytic pathway running. The nonlinear dynamical model combines the network of glycolysis and the additional pathways of the xenobiotics to predict the asymmetric yield (enantiomeric excess, ee) of L-versus D-carbinol for different environmental conditions (Fig. 3.4). Here, the enantiomeric excess of fluxes vy and i>d is defined as... 

There are two other cofactors that can participate in redox processes these are /lavin adenine dinucleotide (FAD) and nicotinamide adenine dinucleotide phosphate (NADP+). both of which are shown in Fig. 11-2. FAD accepts 2H s and is thereby reduced to FADH2, whereas NADP+ accepts H and is reduced to NADPH and H +. Both of these reduced cofactors can be oxidized, thereby donating their H s (or reducing equivalents), similar to the oxidation of NADH. The enzymes that catalyze those reactions involving an oxidation or a reduction are usually very selective toward a particular cofactor (NAD or NADP) in a particular oxidation state. 

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