Nicotinamide adenine dinucleotide oxidizing agents

The most important product of the hexose monophosphate pathway is reduced nicotinamide-adenine dinucleotide phosphate (NADPH). Another important function of this pathway is to provide ribose for nucleic acid synthesis. In the red blood cell, NADPH is a major reducing agent and serves as a cofactor in the reduction of oxidized glutathione, thereby protecting the cell against oxidative attack. In the syndromes associated with dysfunction of the hexose monophosphate pathway and glutathione metabolism and synthesis, oxidative denaturation of hemoglobin is the major contributor to the hemolytic process. 

Metabolism of trimethylamine oxide in fish muscle involves an enzyme-catalyzed oxidation-reduction reaction. The enzyme responsible for the conversion of trimethylamine oxide to trimethylamine is known as trimethylamine-W-oxide reductase. This enzyme acts on nicotinamide adenine dinucleotide (NADH) and TMAO to produce NAD+, trimethylamine and water (Fig. 13.13.1). TMAO acts as the oxidizing agent and is reduced, while NADH undergoes oxidation as the reducing agent. 

NAD is one of Nature s most important oxidizing agents it can be considered as a biological equivalent of the chromium(VI) ion. NAD is shorthand for nicotinamide adenine dinucleotide it is a co-enzyme, which together with an enzyme is essential for several life-sustaining processes (Box 2.2). On reduction it forms the corresponding 1,4-dihydropyridine, NADH, The oxidation of ethanol to acetaldehyde (ethanal) is effected by the enzyme alcohol dehydrogenase and mediated by NAD (Scheme 2.31). 

An important group of biological oxidizing agents includes the pyridine nucleotides, of which nicotinamide adenine dinucleotide (NAD , 13) is an example ... 

Alcohol dehydrogenase catalyzes an oxidation the removal of two hydrogen atoms from the alcohol molecule. The oxidizing agent is nicotinamide adenine dinucleotide (NAD). NAD exists in two forms the oxidized form, called NAD+, and the reduced form, called NADH. The following equation shows that ethanol is oxidized to acetaldehyde, and NAD+ is reduced to NADH. 

Photodissociation of dimer coupled to current measurement of electrochemical oxidation of the pyridinyl radical to the pyridinium ion has been described in Section 3.1.3. Oxidation of the l-methyl-3-carbamidopyridinyl and NAD (nicotinamide adenine dinucleotide radical) after dissociation of the dimers has been reported the agents being either oxygen or OH radical. Reasonable mechanisms for the latter are either electron transfer or radical combination, followed by dissociation to Py+ and OH. 

The oxidizing agent is a compound that, like ATP, constantly appears in these reactions nicotinamide adenine dinucleotide (NAD). The functional group here, we remember (Sec. 36.15), is the pyridine ring, which can accept a hydride ion to form NADH. Like the hemiacetal moiety, NAD is bound to the enzyme, and in a position for easy reaction (Fig. 37.3). 

Note how the above reactions are written. It s common when writii biochemical transformations to show only the structures of the reactant and product, whUe abbreviating the structures of coenzymes and other reactants. The curved arrow intersecting the usual strsiight reaction arrow io the first step shows that ATP is also a reactant and that ADP is a product. The coenzyme nicotinamide adenine dinucleotide (NAD ) is required in the second step, and reduced nicotinamide adenine dinucleotide (NADH) plus a proton are products. We ll see shortly that NAD is often involved as a biochemical oxidizing agent for converting alcohols to ketones or aldehydes. 

The simplest example of such reactions is the decarboxylation of pyruvate. Both model and enzyme studies have shown the intermediacy of covalent complexes formed between the cofactor and the substrate. Kluger and coworkers have studied extensively the chemical and enzymatic behavior of the pyruvate and acetaldehyde complexes of ThDP (2-lactyl or LThDP, and 2-hydroxyethylThDP or HEThDP, respectively) . As Scheme 1 indicates, the coenzyme catalyzes both nonoxidative and oxidative pathways of pyruvate decarboxylation. The latter reactions are of immense consequence in human physiology. While the oxidation is a complex process, requiring an oxidizing agent (lipoic acid in the a-keto acid dehydrogenases , or flavin adenine dinucleotide, FAD or nicotinamide adenine dinucleotide , NAD " in the a-keto acid oxidases and Fe4.S4 in the pyruvate-ferredoxin oxidoreductase ) in addition to ThDP, it is generally accepted that the enamine is the substrate for the oxidation reactions. 

The structure of the oxidized form of nicotinamide adenine dinucleotide is shown in Figure 15.3. The only portion of the coenzyme that undergoes chemical change in the reaction is the substituted pyridine ring of the nicotinamide unit (shown in red in Figure 15.3). If the remainder of the coenzyme molecnle is represented by R, its role as an oxidizing agent is shown in the equation... 

Oxygen gas is not used as the oxidizing agent in the metabolism of food. The oxidizing agent used in the cell is called nicotinamide adenine dinucleotide (NAD). 

Recently, in an approach to explain the diverse actions of polyphenols, Howitz et al. suggested that the antiproliferative and oncosuppressive properties of resveratrol might be due to a mechanism that mimics caloric restriction and lifespan extension, and involves the sirtuin (SIRT) family of nicotinamide adenine dinucleotide (NAD) -dependent acety-lases (Howitz et al. 2003). More specifically, resveratrol was found to directly interact with SIRTl deacetylase, resulting in decreased acetylation of p53, increased DNA stability, and finally cell survival. Redox formation was implicated in the inhibition of histone deacetylase (HDAC) activity, leading to a chronic inflammatory-like response (Rahman et al. 2004). In this respect, resveratrol is a promising agent in the reversal of oxidative stress and rescue of mutant phenotypes. 

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