Reduction nicotinamide nucleotide

Pseudomonas and Azotobacter transhydrogenases was provided by Cohen and Kaplan (17) and by van den Broek et al. [19), respectively, who showed that inactivation by heat treatment could be reversed by addition of FAD. FAD could not be replaced by FMN. Reduction of the enzyme with either NADH or NADPH largely increased the heat sensitivity, whereas oxidized nicotinamide nucleotides or FAD had the opposite effect (17, 19). The number of flavins per 50,000-dalton molecular weight was calculated to be 0.58 to 1.1 (17). 

The metabolic function of the flavin coenzymes is as electron carriers in a wide variety of oxidation and reduction reactions central to aU metabolic processes, including the mitochondrial electron transport chain. Unlike the nicotinamide nucleotide coenzymes (Section 8.4.1), which act as cosubstrates, leaving the catalytic site of the enzyme at the end of the reaction, the flavin coenzymes remain bound to the enzyme throughout the catalytic cycle. 

As shown in Figure 7.4, flavins can undergo a one-electron reduction to the semiquinone radical or a two-electron reduction to dihydroflavin. This means that flavins can act as intermediates between obligatory two-electron redox reactions involving nicotinamide nucleotides (Section 8.4.1) and obligatory one-electron reactions involving cytochromes, iron-sulfur proteins, and ubiquinone (Section 14.6). 

Nicotinamide is the reactive moiety of the nicotinamide nucleotide coenzymes NAD (nicotinamide adenine dinucleotide) and NADP (nicotinamide adenine dinucleotide phosphate), which are coenzymes (or more correctly cosubstrates) in a wide variety of oxidation and reduction reactions (Section 8.4.1). The notation NAD(P) is used to mean either NAD or NADP, without specifying the oxidation state. 

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. 

Although the nicotinamide nucleotide coenzymes function in a large number of oxidation and reduction reactions, thus carmot be exploited as a means of assessing the state of the body s niacin reserves, because the coenzymes are not firmly attached to their apoenzymes, as are coenzymes derived from thiamin (Section 6.5.3), riboflavin (Section 7.5.3), and vitamin Be (Section 9.5.3), but act as cosubstrates of the reactions, binding to and leaving the enzyme as... 

Nicotinamide nucleotide transhydrogenase (EC 1.6.1.1) catalyzes the reversible reduction of NADP" by NADH according to the reaction... 

The photoreduction of some N substituted nicotinamides has been studied, as a model of pyridine nucleotide reductions.32 5 Bonneau and his group >67 have continued their investigations on the pH dependence of the photoreduction of thiazine dyes in aqueous solutions, using edta as an electron donor. Reductive ring cleavage of 3,5-dimethylisoxazole (29) to (30) occurs on irradiation in... 

In some metabolic oxidation and reduction reactions the hydrogen acceptor or donor is a prosthetic group, e.g. haem (section 2.4.1.1) or riboflavin (section 2.4.1.2). In other cases, the hydrogen acceptor or donor acts as a substrate of the enzyme (e.g. the nicotinamide nucleotide coenzymes section 2.4.1.3). 

Unlike flavins and metal coenzymes, the nicotinamide nucleotide coenzymes do not remain bound to the enzyme, but act as substrates, binding to the enzyme, undergoing reduction and then leaving. The reduced coenzyme is then reoxidized either by reaction with another enzyme, for which it acts as a hydrogen donor, or by way of the mitochondrial electron transport chain (section 3.3.1.2). Cells contain only a small amount of NAD(P) (of the order of400 nmol/g in liver), which is rapidly cycled between the oxidized and reduced forms by different enzymes. 

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... 

In the transfer of reducing equivalents from the pyridine nucleotide pool, flavoproteins carry out a central role of mediating the conversion of the obligatory 2-electron reductant to 1-electron receptors such as hemes and iron-sulfur redox centers. In such a role, the semiquinone form of the flavin serves as a pivotal intermediate. The reduction of flavins and flavoproteins by reduced pyridine nucleotides has been extensively studied since the initial work of Singer and Kearney which showed that flavin reduction can occur in a non-enzyme catalyzed manner. The reduction proceeds as a 2-electron process since the formation of a nicotinamide semiquinone (a necessary intermediate in a 1-electron process) has been... 

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