Pyridine nucleotide

Coemymes effecting transfer of hydrogen. These include the pyridine nucleotides, nicotinamide-adenine dinucleolide and nicotinamide-adenine dinucleolide phosphate the flavin nucleotides such as flavin-adenine dinucleotide and lipoic acid. 

A popular alternative to the step utili2ing chromogen is to substitute -hydroxyben2enesulfonate for phenol in the reaction with the pyridine nucleotide ... 

Flavin adenine dinucleotide (FAD) has been electropolymerized using cyclic voltammetry. Cyclic voltammograms of poly (FAD) modified electrode were demonstrated dramatic anodic current increasing when the electrolyte solution contained NADH compare with the absence of pyridine nucleotide. 

FIGURE 18.10 Hydrogen and electrons released in the course of oxidative catabolism are transferred as hydride ions to the pyridine nucleotide, NAD, to form NADH -t- H in dehydrogenase reactions of the type... 

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... 

Riboflavin was first isolated from whey in 1879 by Blyth, and the structure was determined by Kuhn and coworkers in 1933. For the structure determination, this group isolated 30 mg of pure riboflavin from the whites of about 10,000 eggs. The discovery of the actions of riboflavin in biological systems arose from the work of Otto Warburg in Germany and Hugo Theorell in Sweden, both of whom identified yellow substances bound to a yeast enzyme involved in the oxidation of pyridine nucleotides. Theorell showed that riboflavin 5 -phosphate was the source of the yellow color in this old yellow enzyme. By 1938, Warburg had identified FAD, the second common form of riboflavin, as the coenzyme in D-amino acid oxidase, another yellow protein. Riboflavin deficiencies are not at all common. Humans require only about 2 mg per day, and the vitamin is prevalent in many foods. This vitamin... 

Steric Specificity for NAD of Various Pyridine Nucleotide-Linked Enzymes... 

Niacin (Fig. 1) is a collective name for all vitamers having the biological activity associated with nicotinamide (= pyridine-3-carboxamide), including nicotinic acid (= pyridine-3-carboxylic acid) and a variety of pyridine nucleotide structures. 

Nicotinate and pyridine nucleotide metabolism in Escherichia coli and Saccharomyces cerevisiae (Unkefer and London 1984)... 

Xanthobacter sp. strain Py2 may be grown with propene or propene oxide. On the basis of amino acid sequences, the monooxygenase that produces the epoxide was related to those that catalyzes the monooxygenation of benzene and toluene (Zhou et al. 1999). The metabolism of the epoxide is initiated by nucleophilic reaction with coenzyme M followed by dehydrogenation (Eigure 7.13a). There are alternative reactions, both of which are dependent on a pyridine nucleotide-disulfide oxidoreductase (Swaving et al. 1996 Nocek et al. 2002) ... 

Swaving J, JAM de Bont, A Westphal, A de Kok (1996) A novel type of pyridine nucleotide-disulfide oxidore-ductase is essential for NAD - and NADPH-dependent degradation of epoxyalkanes by Xanthobacter strain Py2. J Bacteriol 178 6644-6646. 

M. Ju.szczuk and A. M. Rychter, Changes in pyridine nucleotide levels in leaves and roots of bean plants Phaseolus vtilgans L.) during phosphate deficiency. J. Plant Physiol. 151 399 (1997). 

Nitrosoarenes are readily formed by the oxidation of primary N-hydroxy arylamines and several mechanisms appear to be involved. These include 1) the metal-catalyzed oxidation/reduction to nitrosoarenes, azoxyarenes and arylamines (144) 2) the 02-dependent, metal-catalyzed oxidation to nitrosoarenes (145) 3) the 02-dependent, hemoglobin-mediated co-oxidation to nitrosoarenes and methe-moglobin (146) and 4) the 0 2-dependent conversion of N-hydroxy arylamines to nitrosoarenes, nitrosophenols and nitroarenes (147,148). Each of these processes can involve intermediate nitroxide radicals, superoxide anion radicals, hydrogen peroxide and hydroxyl radicals, all of which have been observed in model systems (149,151). Although these radicals are electrophilic and have been suggested to result in DNA damage (151,152), a causal relationship has not yet been established. Nitrosoarenes, on the other hand, are readily formed in in vitro metabolic incubations (2,153) and have been shown to react covalently with lipids (154), proteins (28,155) and GSH (17,156-159). Nitrosoarenes are also readily reduced to N-hydroxy arylamines by ascorbic acid (17,160) and by reduced pyridine nucleotides (9,161). 

Mammalian thioredoxin reductases are a family of selenium-containing pyridine nucleotide-disulfide oxidoreductases. These enzymes catalyze NADPH-dependent reduction of the redox protein thioredoxin (Trx), which contains a redox-active disulfide and dithiol group and by itself may function as an efficient cytosolic antioxidant [77]. One of the functions of Trx/ thioredoxin reductase system is the NADPH-catalyzed reduction of protein disulfide [78] ... 

The MTHFRs of Arabidopsis and maize have recently been cloned by genomics-based approaches, based on homology with the enzymes from other organisms.17 Like mammalian MTHFRs, the plant enzymes were found to be homodimers of two-domain subunits that are homologous to the mammalian enzymes throughout both domains. However, when the recombinant plant proteins were expressed in yeast, they were found to differ radically from the mammalian MTHFRs in both their pyridine nucleotide preference and their regulatory properties plant enzymes prefer NADH to NADPH, and they are insensitive to AdoMet.17... 

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. 

Alcohol dehydrogenases catalyze oxidation of alcohols in a reaction dependent on the pyridine nucleotide NAD+ [Eq. (5)]. Since the reaction is reversible, alcohol dehydrogenases also catalyze the reduction of aldehydes by... 

The carbonyl reductases catalyze reduction of aldehydes and ketones by reduced pyridine nucleotides (NADH and/or NADPH). As mentioned earlier, alcohol dehydrogenase can perform this function in the presence of a high ratio of NADH to NAD+. Other enzymes capable of carbonyl reduction include the aldehyde and ketone reductases. The aldehyde and ketone reductases have a ubiquitous species distribution, with the enzymes present in organisms ranging from bacteria to vertebrates. The mammalian carbonyl reductases have been extensively reviewed (101). 

Indicine IV-oxide (169) (Scheme 36) is a clinically important pyrrolizidine alkaloid being used in the treatment of neoplasms. The compound is an attractive drug candidate because it does not have the acute toxicity observed in other pyrrolizidine alkaloids. Indicine IV-oxide apparently demonstrates increased biological activity and toxicity after reduction to the tertiary amine. Duffel and Gillespie (90) demonstrated that horseradish peroxidase catalyzes the reduction of indicine IV-oxide to indicine in an anaerobic reaction requiring a reduced pyridine nucleotide (either NADH or NADPH) and a flavin coenzyme (FMN or FAD). Rat liver microsomes and the 100,000 x g supernatant fraction also catalyze the reduction of the IV-oxide, and cofactor requirements and inhibition characteristics with these enzyme systems are similar to those exhibited by horseradish peroxidase. Sodium azide inhibited the TV-oxide reduction reaction, while aminotriazole did not. With rat liver microsomes, IV-octylamine decreased... 

Isselbacher, K. J., and McCarthy, E. A., The influence of pyridine nucleotides on galactose-1-C14 oxidation to C1402 in vitro. Biochem. Biophys. Research Cotn-muns. 1, 49-53 (1959). 

D7. Dietrich, L. S., Friedland, I. M., and Kaplan, L. A., Pyridine nucleotide metabolism mechanism of action of the niacin antagonist, 6-amino-nicotinamide. ]. Biol. Chem. 233, 964-968 (1958). 

Mechanism of Hydrogen Transfer by Pyridine Nucleotide Coenzymes 239... 

Fig. 1. General scheme of the hydrogen transfer as catalyzed by dehydrogenase reactions. R represents the residue of the pyridine nucleotide molecule.

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