Nicotinic acid metabolite

Urinary excretions of nicotinic acid metabolites and 2-pyridone, as well as of 4-pyridoxic and xanthurenic acids were determined in 15 South African Bantu pellagrins before and after tryptophan administration (P13). Red blood cell riboflavine levels and serum glutamic-oxalacetic transaminase levels were also measured. The authors discussed the apparent inability of the pellagra patients to convert tryptophan to nicotinic acid as indicated by their low excretion of nicotinic acid metabolites before and after tryptophan load. The possibility that the subjects were also suffering from a riboflavine deficiency was also discussed. 

FIGURE I A reconstructed extracted ion chromatogram of nicotinic acid and its six metabolites under HILIC conditions. Column Hypersil silica (4.6 X 50 mm) at a flow rate of 4 mL/min. Mobile phase A is water, mobile phase B is acetonitrile, both containing 1% formic acid. Gradient is 0.01-0.25 min 90% B to 65% B 0.25-0.90 min 65% B to 50% B. NA nicotinic acid NAM nicotinamide NUA nicotinuric acid 2-PY l-methyl-2-pyridone-5-carboxamide l-MNAM I-methyl-nicotinamide NAMO nicotinamide-N-oxide 4-PY l-methyl-4-pyridone-5-carboxamide. (Reprinted with permission from Reference 20.)... 

An intriguing feature of nicotinic acid formation in animals is that it is a metabolite produced from the amino acid tryptophan. This means the pyridine ring is actually formed by biochemical modification of the indole fused-ring system (see Section 11.8.2), and, as you might imagine, it involves a substantial sequence of transformations. 

NT259 Ringdahl, B. E., G. K. Johnson, R. B. Ali, and C. C. Organ. Effect of nicotine on arachidonic acid metabolites and epithelial parameters in rat oral mucosa. J Oral Pathol Med 1997 26(1) 40-45. 

Nicotine forms a number of metabolites in the body, mainly in the liver. Approximate 75% of nicotine is oxidized to cotinine, which is the primary nicotine metabolite. Cotinine can be measured in the blood, urine, and saliva and this is used as a measure of nicotine exposure in tobacco users and in those exposed to secondhand smoke. The oxidation of nicotine also produces nicotinic acid. Nicotinic acid is vitamin B3 and has the common name niacin. Niacin deficiency results in a disease called pellagra, which is found in certain malnourished populations. Pellagras symptoms include dermatitis, diarrhea, sensitivity to light, and dementia. 

Hsieh, Y., and Chen, J. (2005). Simultaneous determination of nicotinic acid and its metabolites using hydrophilic interaction chromatography with tandem mass spectrometry. Rapid Commun. Mass Spectrom. 19 3031-3036. 

The most generally interesting intracellular metabolites are the adenine nucleotide phosphates (ATP/ADP/AMP) and the nicotinic acid/adenine dinucleotide phosphates (NAD(P)H/NAD(P)). The pool concentrations and ratios of these can serve as markers for the physiological status of a culture. 

Navazio, L., Bewell, M.A., Siddiqua, A., Dickinson, G.D., Galione, A., and Sanders, D., 2000, Calcium release from the endoplasmic reticulum of higher plants elicited by the NADP metabolite nicotinic acid adenine dinucleotide phosphate. Proc. Natl. Acad. Sci. USA. 97 8693-8698. 

Figure 8.3. Metabolites of nicotinamide and nicotinic acid. Nicotinamide deamidase (nicotinamidase), EC 3.5.1.19 nicotinamide Af-methyltransferase, EC 2.1.1.1 aldehyde dehydrogenase, EC 1.1.1.1. Relative molecular masses (Mr) nicotinamide, 123.1 nicotinic acid, 122.1 nicotinamide JV-oxide, 139.1 Af -methyl nicotinamide, 139.1 trigonelline, 137.1 nicotinuric acid, 179.2 and methyl pyridone carboxamides, 154.1.

Disposition in the Body. Readily absorbed after oral administration. Metabolised to A -methylnicotinamide, A-methyl-6-oxo-pyridine-3-carboxamide, iV-methyl-4-oxopyridine-3-carbox-amide, and by glycine conjugation to nicotinuric acid. It is rapidly excreted in the urine, and after administration of therapeutic doses about 34% is excreted unchanged in 6 hours. Nicotinic acid is a metabolite of nicergoline, nicotinamide, and nicotinyl tartrate. 

It was furthermore reported (K20) that nicotinic acid-deficient animals would grow only if given tryptophan, thus suggesting the conversion of tryptophan to nicotinic acid. Not only is tryptophan converted to nicotinic acid but also kynurenine and 3-hydroxyanthranilic acid. The peculiar degradation of the latter to pyridine derivatives gave rise to many interesting investigations. 3-Hydroxyanthranilic acid is derived from 3-hydroxykynurenine, another important tryptophan metabolite, the his-... 

All. Auricchio, S., Quagliariello, E., and Rubino, A., On the presence of metabolites of the tryptophan-nicotinic acid chain in the urine of sucklings during the first month of life. Helv. Paediat. Acta 15, 479-486 (1960). 

Conversion of nicotinic acid to NAD is illustrated by the following experiment involving mice (Figure 9.63), The animals were injected with carbon-14-labeled nicotinic acid. The livers were removed at the indicated times — 0.33,1.0,3.0, and 10 minutes — and used for analysis of the radioactive metabolites. At 20 seconds, unchanged nicotirric acid (O) w as the major metabolite. At 1 to 3 minutes, there was a temporary accumulation of nicotinic acid ribonucleotide (V) and deamjdo-NAD (A). NAD ( ) was the major metabolite after 3 minutes. 

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. ... 

Iwaki M, Murakami E, Kakehi K. Chromatographic and capillary electrophoretic methods for the analysis of nicotinic acid and its metabolites. J Chromatogr B Biomed Sci Appl 2000 747 229-40. 

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