Nicotinic acid, nicotinamide phosphate

BiosytMesis In animals tryptophan - kynutenine - 3-hydroxyanthranilic acid - quinolinic acid (pyri-dine-2,3-dicaiboxylic acid) - nicotinic acid - nicotinamide. In bacteria and higher plants from L- aspar-tic acid and a C3-unit, probably D-glyceraldehyde 3-phosphate. Also by cleavage of NAD. 

The biological importance of these compounds stems from their use as cofactors. Both nicotinamide and nicotinic acid ate building blocks for coen2yme I (Co I), nicotinarnide—adenine dinucleotide (NAE)) (3) and coen2yme II (Co II), nicotinarnide—adenine dinucleotide phosphate (NAE)P) (4) (2). 

Nicotinic acid derivatives occur in biologic materials as the free acid, as nicotinamide, and in two coenzymatic forms nicotinamide adenine dinucleotide (NAD), and nicotinamide adenine dinucleotide phosphate (NADP). These coenzymes act in series with flavoprotein enzymes and, like them, are hydrogen acceptors or, when reduced, donors. Several plants and bacteria use a metabolic pathway for the formation of nicotinic acid that is different from the tryptophan pathway used by animals and man (B39). 

Group-transfer reactions often involve vitamins3, which humans need to have in then-diet, since we are incapable of realizing their synthesis. These include nicotinamide (derived from the vitamin nicotinic acid) and riboflavin (vitamin B2) derivatives, required for electron transfer reactions, biotin for the transfer of C02, pantothenate for acyl group transfer, thiamine (vitamin as thiamine pyrophosphate) for transfer of aldehyde groups and folic acid (as tetrahydrofolate) for exchange of one-carbon fragments. Lipoic acid (not a vitamin) is both an acyl and an electron carrier. In addition, vitamins such as pyridoxine (vitamin B6, as pyridoxal phosphate), vitamin B12 and vitamin C (ascorbic acid) participate as cofactors in an important number of metabolic reactions. 

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. ... 

Fig. 3 Electropherogram of five water-soluble vitamines thiamine (cationic), nicotinamide (nonionic), biotin (anionic), ascorbic acid (anionic), and nicotinic acid (anionic) in 20 mM phosphate run buffer at pH 8.0.

Niacin is also known as vitamin PP or vitamin Bj. The term niacin describes two related compounds, nicotinic acid and nicotinamide (Figure 19.18), both with biological activity. Niacin is formed from the metabolism of tryptophan, and therefore it is not strictly a vitamin. It is a precursor of two cofactors nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are essential for the functioning of a wide range of enzymes involved in redox reactions. 

Niacin is a generic term which refers to two related chemical compounds, nicotinic acid (6.22) and its amide, nicotinamide (6.23) both are derivatives of pyridine. Nicotinic acid is synthesized chemically and can be easily converted to the amide in which form it is found in the body. Niacin is obtained from food or can be synthesized from tryptophan (60 mg of dietary tryptophan has the same metabolic effect as 1 mg niacin). Niacin forms part of two important co-enzymes, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), which are co-factors for many enzymes that participate in various metabolic pathways and function in electron transport. 

Two vitamins, nicotinamide and pyridoxine (vitamin B6), are pyridine derivatives. Nicotinamide participates in two coenzymes, coenzyme I (65 R = H) which is known variously as nicotinamide adenine dinucleotide (NAD) or diphosphopyridine nucleotide (DPN), and coenzyme II (65 R = P03H2) also called triphosphopyridine nucleotide (TPN) or nicotinamide adenine dinucleotide phosphate (NADP). These are involved in many oxidation-reduction processes, the quaternized pyridine system acting as a hydrogen acceptor and hydrogen donor. Deficiency of nicotinamide causes pellagra, a disease associated with an inadequately supplemented maize diet. Nicotinic acid (niacin) and its amide are... 

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). 

NAD A Coenzyme Nicotinamide adenine dinucleotide (NAD) is one of the principal oxidation-reduction reagents in biological systems. This nucleotide has the structure of two D-ribose rings (a dmucleotide) linked by their 5 phosphates. The aglycone of one ribose is nicotinamide, and the aglycone of the other is adenine. A dietary deficiency of nicotinic acid (niacin) leads to the disease called pellagra, caused by the inability to synthesize enough nicotinamide adenine dinucleotide. 

NAADP, nicotinic acid adenine dinucleotide 2 -phosphate NAADP-R, nicotinic acid adenine dinucleotide 2 -phosphate receptor nACh-R, nicotinic acetylcholine receptor NADH DH, NADH dehydrogenase NADH/NAD"1", reduced/oxidized nicotinamide adenine dinucleotide NADH-U() OR, NADH-ubiquinone oxidoreductase... 

Niacin is unusual among the vitamins in that it was discovered as a chemical compound, nicotinic acid produced by the oxidation of nicotine, in 1867 -long before there was any suspicion that it might have a role in nutrition. Its metabolic function as part of what was then called coenzyme II [nicotinamide adenine dinucleotide phosphate (NADP)] was discovered in 1935, again before its nutritional significance was known. 

The nicotinamide nucleotide coenzymes function as electron carriers in a wide variety of redox reactions. In addition, NAD is the precursor of adenine dinucleotide phosphate (ADP)-ribose for ADP-ribosylation and poly(ADP-ribosylation) of proteins and cADP-ribose and nicotinic acid adenine dinucleotide phosphate (NAADP). They act as second messengers and stimulate increases in intracellular calcium concentrations. 

Exchange of the nicotinamide moiety of NADP for nicotinic acid, forming NAADP. Early studies also showed that the enzyme can catalyze exchange of nicotinamide with a variety of other bases, including histamine. Formation of histamine adenine dinucleotide phosphate was thought to provide an alternative to amine oxidase for rapid inactivation of histamine. 

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. ... 

Figure 11.9. ISAD synthesis pathway from nicotinamide or niacin (l)nicoti-namidase (E.C. 3.5.1.19) (2)nicotinamide phosphoribosyl transferase, which requires ATP (3)1SIMN adenyl transferase, which requires ATP (4) nicotinic acid phosphoribosyl transferase, which requires ATP (5) NMN adenyl transferase, which requires ATP (6) NAD synthetase, which requires ATP. Ri, ribose P, phosphate Ad, adenine NMN, nicotinamide mononucleotide. This figure is from Ref 33 and is used with permission.

Niacin and niacinamide (nicotinamide and nicotinic acid amide) are converted to the ubiquitous redox coenzymes nicotinamide-adenine dinucleotide (NAD)" and nicotinamide-adenine dinucleotide phosphate (NADP). ... 

Nicotinamide-adenine dinucleotide (NAD diphosphopyri-dine nucleotide) and nicotinamide-adenine dinucleotide phosphate (NADP also termed triphosphopyridine nucleotide) represent most of the niacin activity found in good sources that include yeast, lean meats, liver, and poultry. Milk, canned salmon, and several leafy green vegetables contribute lesser amounts but are still sufficient to prevent deficiency. Additionally, some plant foodstuffs, especially cereals such as corn and wheat, contain niacin bound to various peptides and sugars in forms nutritionally not readily available (niacinogens or niacytin). Because tryptophan is a precursor of niacin, protein provides a considerable portion of niacin equivalent. As much as two thirds of niacin required by adults can be derived from tryptophan metaboHsm via nicotinic acid ribonucleotide... 

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