Nicotinamide adenine dinucleotide phosphate catabolism

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... 

Endogenous NO is produced almost exclusively by L-arginine catabolism to L-citrul-line in a reaction catalyzed by a family of nitric oxide synthases (NOSs) [3]. In the first step, Arg is hydroxylated to an enzyme-bound intermediate "-hydroxy-1.-arginine (NHA), and 1 mol of NADPH (nicotinamide adenine dinucleotide phosphate, reduced form) and O2 are consumed. In the second step, N H A is oxidized to citrulline and NO, with consumption of 0.5 mol of NADPH and 1 mol of 02 (Scheme 1.1). Oxygen activation in both steps is carried out by the enzyme-bound heme, which derives electrons from NADPH. Mammalian NOS consists of an N-terminal oxy-... 

Two important implications of the reactions described in Equations (5.1) and (5.2) are (i) that redox reactions play an important role in metabolic transformations, with the cofactors nicotinamide adenine dinucleotide (NAD+) acting as electron acceptor in catabolic pathways and nicotinamide adenine dinucleotide phosphate (NADPH) as electron donor in anabolism, and (ii) that energy must be produced by catabolism and used in biosyntheses (almost always in the form of adenosine triphosphate, ATP). 

The nicotinamide coenzymes nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) are associated with a wide variety of enzymes involved in oxidation-reduction reactions (Fig. 21). NADH is typically involved in oxidative catabolic reactions, while NADPH is primarily used in biosynthetic pathways [58]. 

The relationship between anabolic and catabolic processes is illustrated in Figure 1.20. As nutrient molecules are degraded, energy and reducing power are conserved in ATP and NADH molecules, respectively. Biosynthetic processes use metabolites of catabolism, synthesized ATP and NADPH (reduced nicotinamide adenine dinucleotide phosphate, a source of reducing power, i.e., high-energy electrons), to create complex structure and function. 

Nicotinamide adenine dinucleotide (NAD) is the coenzyme form of the vitamin niacin. Most biochemical reactions require protein catalysts (enzymes). Some enzymes, lysozyme or trypsin, for example, catalyze reactions by themselves, but many require helper substances such as coenzymes, metal ions, and ribonucleic acid (RNA). Niacin is a component of two coenzymes NAD, and nicotinamide adenine dinucleotide phosphate (N/kDP). NAD (the oxidized form of the NAD coenzyme) is important in catabolism and in the production of metabolic energy. NADP (the oxidized form of NADP) is important in the biosynthesis of fats and sugars. 

The electron donor in most reductive biosyntheses is NADPH, the reduced form of nicotinamide adenine dinucleotide phosphate (NADP see Figure 14.13). NADPH differs from NADH in that the 2 -hydroxyl group of its adenosine moiety is esterified with phosphate. NADPH carries electrons in the same way as NADH. However, NADPH is used almost exclusively for reductive biosyntheses, whereas NADH is used primarily for the generation of ATP. The extra phosphoryl group on NADPH is a tag that enables enzymes to distinguish between high-potential electrons to be used in anabolism and those to be used in catabolism. 

Anabolic (biosynthetic) reactions are driven by ATP energy, and the process of reduction is mediated by enzymes most of which utilize nicotinamide adenine dinucleotide phosphate (NADP or NADP+) as cofactor. The specificity of catabolism for NAD+ and anabolism for NADP+ is an example of chemical compartmentation and enables some degree of metabolic regulation to be exerted through control of the levels of the two cofactors. The relative concentrations of the oxidized and reduced forms of a particular cofactor may also serve a regulatory role. 

Whereas catabolism involves oxidation of starting molecnles, biosynthesis or anabolism involves reduction reactions, hence the need for a reducing agent or hydrogen donor, which is usually NADP (nicotinamide adenine dinucleotide phosphate). These catalysts are known as coenzymes and the most widely occurring is coenzyme A (CoA), made up of ADP (adenosine diphosphate) and pantetheine phosphate. 

The pentose phosphate pathway is also known as the hexose monophosphate shunt and the phos-phogluconate pathway because of the variety of intermediates formed by the pathway under different conditons. The pathway which occurs in a wide variety of organisms including animals, plants and microorganisms is classihable as secondary metabolism (Section 10.5) due to the relatively small quantity of glucose catabolized by this route. In mammalian tissues, the pathway yields a number of important products, in particular, reduced nicotinamide adenine dinucleotide phosphate (NADPH) and pentose sugars. 

In contrast to our understanding of the biosynthesis of cofactors, relatively little is known about cofactor degradation. Some previous research has been carried out to identify intermediates on these catabolic pathways, but very little information is available on the genes involved and on the enzymol-ogy. In this chapter we summarize our current understanding of the pyridoxal phosphate, riboflavin, heme, thiamin, biotin, nicotinamide adenine dinucleotide (NAD), folate, lipoate, and coenzyme A catabolic pathways in all life-forms and discuss mechanistic aspects of the most interesting catabolic reactions. 

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