Nicotine adenine dinucleotide, reaction with

On NMR monitoring of the reaction of nicotine adenine dinucleotide (NAD ), an important co-factor in enzymatic reactions, with 43 at pH 6, the formation of two unique diastereomeric cyclic trimeric metallacalixarene systems 49, in a self-assembly mode, was evident (1999JOM(589)66). These products have a narrow stability range at pH 6 and decompose at lower or higher pH. The complex 49 was neither electroactive nor it was possible to convert it to the corresponding NADH-based system (1999JOM(589)66). 

The mechanism of electron transfer reactions in metal complexes has been elucidated by -> Taube who received the Nobel Prize in Chemistry for these studies in 1983 [xiv]. Charge transfer reactions play an important role in living organisms [xv-xvii]. For instance, the initial chemical step in -> photosynthesis, as carried out by the purple bacterium R. sphaeroides, is the transfer of electrons from the excited state of a pair of chlorophyll molecules to a pheophytin molecule located 1.7 mm away. This electron transfer occurs very rapidly (2.8 ps) and with essentially 100% efficiency. Redox systems such as ubiquinone/dihydroubiquinone, - cytochrome (Fe3+/Fe2+), ferredoxin (Fe3+/Fe2+), - nicotine-adenine-dinucleotide (NAD+/NADH2) etc. have been widely studied also by electrochemical techniques, and their redox potentials have been determined [xviii-xix]. 

Some oxidoreductases require nicotine adenine dinucleotide (NADH) as a cofactor.146 To use them in organic synthesis, as in the reduction of a ketone to an alcohol, it is necessary to have an efficient system to continuously regenerate them. A common way is to include in the same reaction formic acid and formate dehydrogenase, the byproduct being carbon dioxide.147 The regeneration of the cofactor can also be done electrochemically with or without the addition of a hydrogenase.148 The use of whole organisms eliminates this need. 

Two coenzymes which are involved in most of the redox reactions of metabolism are nicotine adenine dinucleotide, NAD", and FAD, flavine adenine dinucleotide. Most metabolic oxidations are, in fact, dehydrogenations, and not reactions with oxygen. Nicotinamide is derived from nicotinic acid, and the isoalloxazine ring of FAD is derived from riboflavin. Thiamin is the principal cofactor in enzymatic decarboxylations. Many of the vitamins serve as coenzymes in a wide variety of cellular reactions. 

The reaction of [Cp Rh(H2O)3](OT02 with nicotine adenine dinucleotide (NAD ) afforded the cyclic trimer structure, [Cp Rh - VN 1 ) (N6,N7)-9-(5 -ribose pyrophosphate-5"-ribose-T-nicotinamide)adeninato ]3(OTf)3 162, which was fully characterized. ... 

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. 

The answer is a. (Murray, pp 627-661. Scriver, pp 3897-3964. Sack, pp 121—138. Wilson, pp 287-320.) The major contributor of electrons in reductive biosynthetic reactions is nicotinamide adenine dinucleotide phosphate (NADPH -I- H ), which is derived by reduction of NAD. NAD is formed from the vitamin niacin (also called nicotinate). Niacin can be formed from tryptophan in humans. In the synthesis of NAD, niacin reacts with 5-phosphoribosyl-l-pyrophosphate to form nicotinate ribonucleotide. Then, AMP is transferred from ATP to nicotinate ribonucleotide. Finally, the amide group of glutamate is transferred to the niacin carboxyl group to form the final product, NAD. NADP is derived from NAD by phosphorylation of the 2 -hydroxyl group of the adenine ribose moiety. The reduction of NADP to NADPH -I- H occurs primarily through the hexose monophosphate shunt. 

Azaserine, a glutamine antagonist," is known to inhibit the NAD synthetase reaction in which nicotinic acid adenine dinucleotide is converted into NAD with glutamine or ammonia as the nitrogen donor. ° When azaserine or azaleucine was fed to Ricinus communis plants followed by [6- C]quinolinic acid, a marked decrease in incorporation of radioactivity into ricinine was observed with azaleucine, less so with azaserine." Both azaserine and azaleucine were found also to inhibit the incorporation of [6- " C]quinolinic acid into pyridine nucleotide cycle intermediates [in the case of azaserine the conversion of nicotinic acid dinucleotide into nicotinamide adenine dinucleotide (NAD ) was apparently inhibited]. 

As an alternative to nicotinamide, quinolinic acid (a degradation product of tryptophan) may be used to form nicotinic acid mononucleotide (NaMN). Quinolinic acid contains two carboxyl groups one of which is cleaved off during the reaction. All known NMNATs may use NaMN to form a dinucleotide and the subsequent reaction with ATP then yields nicotinic acid adenine dinucleotide, NAAD. This intermediate is the substrate of NAD synthase, an enzyme... 

Figure 3.8. Structures of vitamins or vitamin-derived molecules that function in oxidation-reduction reactions. The oxidation of these redox groups in the inner mitochondricil membrane contributes to the electron transport chain that carries electrons from the oxidation of glucose to oxygen and in the process pumps protons from one side to the other of the inner mitochondrial membrane (see Chapter 8 for details). The proton gradient thus formed is used to phosphorylate ADP to form 32 of the 36 ATPs resulting from the oxidation of one glucose molecule to six CO2 and six H2O molecules. A Vitamin B3, also called niacin or nicotinic acid, becomes converted to the amide (nicotinamide) and dressed up with a ribose sugar. Then, in a manner like that of riboflavin in B becomes phosphorylated to form nicotinamide mononucleotide (NMN) or further reacted with the addition of adenosine monophosphate (AMP) to form nicotinamide adenine dinucleotide (NAD). B Vitamin B2, also known as riboflavin, is shown converted to the forms involved in redox reactions such as those of the electron transport chain. (From Biochemistry, Second Edition, D. Voet and J. Voet, Copyright 1995, John Wiley Sons, New York. Reprinted with permission of John Wiley Sons, Inc.)...

Nicotinic acid mononucleotide reacts with ATP in the presence of nicotinic acid adenine dinucleotide pyrophosphorylase, a magnesium-dependent enzyme, to yield the deamido derivative of NAD (see Fig. 4-11). Deamido NAD, in the presence of ATP, glutamine, Mg, K", and an NAD synthetase, is converted to NAD. In this reaction, the amino group of glutamine is transferred to the carboxyl group of the nicotinic acid moiety of deamido NAD. Yet the nicotinamide moiety of NAD synthetase is found in liver supernatant and, as may be expected, it is inhibited by azaserine. 

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