The Redox Function of NAD P

The nicotinamide coenzymes are involved as proton and electron carriers in a wide variety of oxidation and reduction reactions. Before their chemical structures were known, NAD and NADP were known as coenzymes I and II. Later, when the chemical nature of the pyridine ring of nicotinamide was discovered, they were called diphosphopyridine nucleotide (DPN = NAD) and triphospho-pyridine nucleotide (TPN = NADP). The nicotinamide nucleotide coenzymes are sometimes referred to as the pyridine nucleotide coenzymes. 

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For the efficient electrooxidation of NAD(P)H, mediated electrocatalysis is necessary [22, 170, 171], and a wide range of diffusional mediators has been studied [188-193], Organic compounds that undergo two-electron reduction-oxidation processes and also function as proton acceptors-donors upon their redox transformations (such as ortho- and para-derivatives of quinones, phenylenedi-amines and aminophenols) have been found to be ideal for the mediation of NAD(P)H oxidation, although single-electron-transfer mediators (e.g. ferrocene derivatives) are also capable of oxidizing NAD(P)H [190, 191], Some compounds demonstrate very high rates for the mediated oxidation of NAD(P)H in aqueous solutions [188,189,194,195],... 

Several enzymes such as reductases and dehydrogenases utilize nicotinamide derivatives as reversible carriers of redox equivalents. The reduced dihydronicotinamide moiety NAD(P)H acts by donating a hydride equivalent to other molecules. In the corresponding two-electron oxidized NAD(P) form, the cofactor formally accepts a hydride ion from the substrate. Functional models of such reversible hydride transfer processes are of considerable interest for biomimetic chemistry, and the strategies to regenerate nicotinamide-type cofactors are crucial for the performance of many organic transformations involving biocatalytic key steps 139,140). 

For a copolymer of 4-vinylpyridine and N-(p-vinylben2yl)-3-carbamoyl-l,4-dihy-dropyridine containing both important functions (ligand and redox site) the rate of reduction is again increased These reducing agents are important for the comparison with biological NAD(P)H. 

Regeneration of NAD(P)+ from NAD(P)H is a redox reaction involving the transfer of two electrons and a proton (successively or at once as hydride ion H ) to a suitable acceptor. Most commonly these acceptors are carbonyl functions, molecular oxygen or the anode. Apart from a few exceptions the direct hydride transfer is slow or disadvantageous so that catalytic procedures have to be applied. Here we selected representative examples to give an overview. Excellent review articles are available, tool1-3- 10]... 

Fig. 2. Interplay among superoxide anion, nitric oxide, and eicosanoids in high oxidative stress. The biological function of nitric oxide in target cells is influenced by the cellular redox state. In increased oxidative stress, which results in an oxidizing environment, NO readily form free radicals, including the highly reactive peroxynitrite (OONO ). Peroxynitrite can influence eicosanoid synthesis by interfering with different enzyme systems of the arachidonic acid cascade. Increased free radicals may also catalyze nonenzymic peroxidation of membrane PUFA (e.g., arachidonic acid), resulting in increased production of isoprostanes that possess potent vasoconstrictor activity. PLA, phospholipase NO, nitric oxide NOS, nitric oxide synthase NADPH oxidase, vascular NAD(P)H oxidase 02 , superoxide anion PUFA, polyunsaturated fatty acids EPA, eicosapentaenoic acid DHA, docosahexaenoic acid COX, cyclooxygenase PGI2 synthase, prostacyclin synthase.

It is possible that dietary flavonoids participate in the regulation of cellular function independent of their antioxidant properties. Other non-antioxidant direct effects reported include inhibition of prooxidant enzymes (xanthine oxidase, NAD(P)H oxidase, lipoxygenases), induction of antioxidant enzymes (superoxide dismutase, gluthathione peroxidase, glutathione S-transferase), and inhibition of redox-sensitive transcription factors. 

A different redox system model - the model for NADH - was also described by our group. [16] As electron transfer mediators, FMN and FAD accept two electrons from NAD(P)H and transfer one electron to metal centres in heme-containing proteins, nonheme iron, or molybdenum sites. However, the transfer of electrons between reduced pyridine - dinucleotide cofactors is slow under physiological conditions and must be catalysed by enzymes. Function of these enzymes was mimicked by a modification of the cofactor by a recognition site for its counterpart and, thus, efficient electron transfer was enabled directly. Functionalised 1,4-dihydronicotinamides bearing a recognition unit for flavins were synthesised (Scheme 18). 

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