Nicotinic acid adenine dinucleotide mononucleotide

The result of this biosynthesis is that the product is nicotinic acid mononucleotide rather than free nicotinic acid. Ingested nicotinic acid is converted to nicotinic acid mononucleotide which, in turn, is converted to nicotinic acid adenine dinucleotide. Nicotinic acid adenine dinucleotide is then converted to nicotinamide adenine dinucleotide. If excess nicotinic acid is ingested, it is metabolized into a series of detoxification products (Fig. 4). Physiological metabohtes include /V-methylnicotinamide (19) and A/-methyl-6-pyridone-2-carboxamide (24) (1). 

Figure 6. Proposed pyridine nucleotide cycle. Abbreviations NaMN, nicotinic acid mononucleotide NaAD, nicotinic acid adenine dinucleotide and NAD, oxidized form of nicotinamide adenine dinucleotide.

Nicotinic acid and nicotinamide and their derivatives were analyzed by TLC on MN 300G cellulose plates in various solvent systems (K. Shibata, personal communications, October 16, 2001). The Rf values of nicotinamide adenine dinucleotide phosphate or NADP" (Rf values 0.03, 0.50, and 0.70), nicotinamide adenine dinucleotide or NAD" (Rf values 0.13, 0.61, and 0.58), nicotinic acid adenine dinucleotide (Rf values 0.15, 0.52, and 0.57), nicotinamide mononucleotide (Rf values 0.11, 0.63, and 0.73), nicotinic acid mononucleotide (Rf values 0.13, 0.47, and 0.75), nicotinamide (Rf values 0.87, 0.88, and 0.45), and nicotinic acid (Rf values 0.77, 0.82, and 0.55) are shown in various solvent systems [1 M ammonium acetate-95 % ethanol (3 7), pH 5.0 2-butyric acid-ammonia-water (66 1.7 33), and 600 g of ammonium sulfate in 0.1 M sodium phosphate-2% 1-propanol (pH 6.8), respectively]. The detection is performed by illumination under short-wavelength (257.3 nm) UV light. Urinary metabolites of the vitamin could be analyzed by TLC. ... 

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... 

Quinolinic acid phosphoribosyl transferase (PT) catalyzes the formation of nicotinic acid mononucleotide (NaMN) from quinolinic acid and phosphoribosyl pyrophosphate. The pyridine nucleotide NaMN reacts with ATP (adenosine Hiphos-phate) upon mediation of NaMN adenylyltransferase to form the nicotinic acid adenine dinucleotide (NaAD) (Figure 6.7). The latter is converted to NAD by NAD synthetase. NADP is formed from NAD by the catalysis of NAD kinase. 

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. 

Figure 6.37. A metabolic grid proposed for the biosynthesis and control of metabolism of ricinine. A1—quinolinic acid A2—nicotinic acid mononucleotide A3—nicotinic acid adenine dinucleotide A4—nicotinamide adenine dinucleotide A5—nicotinamide A6—nicotinic acid A7—nicotinamide mononucleotide B1— AT-demethjiiicinine B2— ricinine Cl— N-methylnicotinic acid and C2— AT-methylnicotinamide. pyridine nucleotide cycle and postulated reaction sequence (Nowacki and Waller 1975a). Courtesy of Pergamon Press, Ltd., copyright 1975.

Figure 2 NAD metabolism. Tip = tryptophan, 3-HK = 3-hydroxykynurenine, 3-HA = 3-hydroxyanthranilic acid, ACMS = a-amino-P-carboxymuconate- -semialdehyde, AMS = a-aminomuconate- -semialdehyde, NaMN = nicotinic acid mononucleotide, NMN = nicotinamide mononucleotide, NaAD = nicotinic acid adenine dinucleotide. For other abbreviations, see Figure 1. (1) tryptophan oxygenase [EC 1.13.11.11], (2) formy-dase [EC 3.5.1.9], (3) kynurenine 3-hydroxylase [EC 1.14.13.9], (4) kynureninase [EC 3.7.1.3], (5) 3-hydroxyanthranilic acid oxygenase [EC 1.13.11.6], (6) nonenzymatic, (7) aminocarboxymuconate-semialdehyde decarboxylase [EC 4.1.1.45], (8) quinolinate phos-phoribosyltransferase [EC 2.4.2.19], (9) NaMN adenylyltransferase [EC 2.7.2.18], (10) NAD synthetase [EC 6.3.5.1], (11) NAD kinase [EC 2.7.1.23], (12) NAD" glycohydro-lase [EC 3.2.2.5], (13) nicotinamide methyltransferase [EC 2.2.1.1], (14) 2-Py-forming MNA oxidase [EC 1.2.3.1], (15) 4-Py-forming MNA oxidase [EC number not given], (16) nicotinamide phosphoribosyltransferase [EC 2.4.2.12], (17) NMN adenylytransferase [EC 2.7.71], (18) nicotinate phosphoribosyltransferase [EC 2.4.2.11], (19) nicotinate methyltransferase [EC 2.7.1.7], and nicotinamidase [EC 3.5.1.19]. Solid line, biosynthesis dotted line, catabolism.

Abbreviations NaAD, nicotinic acid adenine dinucleotide NMN, nicotinamide mononucleotide NaMN, nicotinic acid mononucleotide Nam, nicotinamide NiA, nicotinic acid QA, quinoUnic acid MNA, JV -methylnicotinic acid Tg, ttigoneBine = W-methylnicotinic acid Nam N-oxide, nicotinamide iV-oxide NiA V-oxide, nicotinic acid N-oxide 2-Py. iV -methyl-2-pyridone-5-carboxamide 4-Py, JV -methyl-4-pyridone-3-carboxamide NuA, nicotinuric acid. 

Although the structures for molecules having niacin activity are simple, the forms in which they act in human biochemistry are not so simple. Nicotinic acid and nicotinamide are precursors for three complex coenzymes in multiple oxida-tion/reduction (redox) reactions nicotinamide mononucleotide, NMN nicotinamide adenine dinucleotide, NAD+ and nicotinamide adenine dinucleotide phosphate, NADP. I shall use NAD+ as representative of the class. NADH is the corresponding reduced form. ... 

The niacin vitamers in foods include nicotinic acid and nicotinamide (Fig. 4), which occur in limited quantities in the free form, and their coenzymes, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP) (93,96). The nicotinic acid analog of NAD as well as nicotinamide and nicotinic acid mononucleotides also occur in nature. In addition, niacin occurs as nicotinyl esters bound to polysaccharides, peptides, and glycopep-tides, which are known as niacytin and niacynogens, respectively. In general, the niacin vitamers in cereal grains and other seeds are principally the nicotinic acid forms, whereas those in meat and fish are primarily the nicotinamide forms (94,95). 

Bi) is converted to thiamine pyrophosphate simply by the addition of pyrophosphate. It is involved in aldehyde group transfer. Niacin (nicotinic acid) is esterified to adenine dinucleotide and its two phosphates to form nicotinamide adenine dinucleotide. Pyridoxine (vitamin B ) is converted to either pyridoxal phosphate or pyridoxamine phosphate before complexing with enzymes. Riboflavin becomes flavin mononucleotide by obtaining one phosphate (riboflavin 5 -phosphate). If it complexes with adenine dinucleotide via a pyrophosphate ester linkage, it becomes flavin adenine dinucleotide. 

Nicotinic acid or nicotinamide (i) Nicotinamide adenine dinucleotide (ii) Nicotinamide adenine dinucleolide phoiphaie (iii) Nicotinamide mononucleotide Hydrogen Hydrogen Hydrogen (i) Nicotinic ncid or nicotina-roidc 0i) Nucleotides of nicotinamide PtnicUlium spent mycelium Wheat seeds Uver... 

Figure 2 NAD biosynthesis subsystem diagram. Major functional roles are shown by 4-6 letter abbreviations (explained in Table 1) over the colored background reflecting the key aspects or modules (pathways) that comprise NAD biosynthesis in various species. Catalyzed reactions are shown by solid straight arrows, and corresponding intermediate metabolites are shown as abbreviations within ovals Asp, L-aspartate lA, Iminoaspartate Qa, quinolinic acid Nm, nicotinamide Na, nicotinic acid NaMN, nicotinic acid mononucleotide NMN, nicotinamide mononucleotide RNm, N-ribosyInicotinamide NaAD, nicotinate adenine dinucleotide NAD, nicotinamide adenine dinucleotide NADP, NAD-phosphate Trp, tryptophan FKyn, N-formylkynurenine Kyn, kynurenine HKyn, 3-hydroxykynurenine HAnt, 3-hydroxyanthranilate and ACMS, a-amino-/3-carboxymuconic semialdehyde. Unspecified reactions (including spontaneous transformation and transport) are shown by dashed arrows.

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.)...

In most bacteria and in higher plants nicotinic acid is formed from aspartic acid and a three carbon unit derived from glycerol, probably D-glyceraldehyde-3-phosphate (D 2). A key intermediate is quinolinic acid, which in animals, however, is derived from l-tryptophan (D 21). Nicotinic acid originates from quinolinic acid via nicotinic acid mononucleotide formed with the participation of 5-phosphoribosyl-l-pyrophosphate. It changes either directly to nicotinic acid or is formed via nicotinamide adenine dinucleotide (NAD+) in the nicotinic acid nucleotide cycle. 

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