Nicotinic acid and nicotinamide

Both these so-called vitamin PP-active substances are soluble in water and alcohol. 

A semi-quantitative estimation is possible by visual comparison of the spots with those from a series of standards (nicotinic acid, 0.1 to 2[xg nicotinamide, 0.5—10 (xg) [96]. Strohecker and Henning s proposal [130] permits very precise determination. The zones of active substance are localised in UV light, scraped off and determined photometrically or polarographicaUy after elution. It is advisable to treat the pure standards in an exactly parallel way and to take these results into account. According to recent data of Strohecker [131], nicotinic acid (50—100 [jLg/10 ml), eluted with IN hydrochloric acid, can be conveniently determined by spectrophotometry at 262 nm a blank must be measured on the same amount of adsorbent. 

Vitamin Bg-active factors are derived from pyridoxine and can be easily extracted with water. The compounds are destroyed in alkaline or neutral solution under the influence of light. 

A selection of TLC systems is given in Table 52. It is evident that the Bg derivatives can be cleanly separated except pyridoxine and its aldehyde which migrate equally fast on almost all layers. Pyridoxine and pyridoxamine, after having been dissolved in hot methanol, can be 

53 = Cellulose powder (over 300 mesh, Toyo Roshi Co.), activated 

Nicotinic acid (melting point 236°C, density 1.473) and nicotinamide (melting point 129°C, density 1.400) are known as niacin and niacinamide in the food industry. Niacin is the most stable of all vitamins and is essential to humans and animals for growth and health. Niacin and niacinamide are nutritionally equivalent, and compete with one another. 

For production of niacinamide in the past, methylethylpyridine was oxidized with nitric acid to yield niacin, and P-picoline was treated with air and ammonia to produce the nitrile that was then hydrolyzed to niacinamide. A more modern process can produce both niacin and niacinamide from a single feedstock, either P-picoline or 2-methyl-5-ethylpyridine by oxidative ammonolysis, a combination of oxidation and animation. 

Either niacin or niacinamide can be selectively isolated from the hydrolysis by varying the hydrolysis time and nitrile concentration. A higher hydrolysis temperature favors production of niacin. 

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Both nicotinic acid and nicotinamide have been assayed by chemical and biological methods. Owing to the fact that niacin is found in many different forms in nature, it is important to indicate the specific analyte in question. For example, if biological assay procedures are used, it is necessary to indicate whether the analysis is to determine the quantity of nicotinic acid or if niacin activity is the desired result of the analysis. If nicotinic acid is desired, then a method specific for nicotinic acid should be used. If quantitation of niacin activity is the desired outcome, then all compounds (bound and unbound) which behave like niacin will assay biologically for this substance (1). 

For more specific analysis, chromatographic methods have been developed. Using reverse-phase columns and uv detection, hplc methods have been appHed to the analysis of nicotinic acid and nicotinamide in biological fluids such as blood and urine and in foods such as coffee and meat. Derivatization techniques have also been employed to improve sensitivity (55). For example, the reaction of nicotinic amide with DCCI (AT-dicyclohexyl-0-methoxycoumarin-4-yl)methyl isourea to yield the fluorescent coumarin ester has been reported (56). After separation on a reversed-phase column, detection limits of 10 pmol for nicotinic acid have been reported (57). 

Owing to poor volatihty, derivatization of nicotinic acid and nicotinamide are important techniques in the gc analysis of these substances. For example, a gc procedure has been reported for nicotinamide using a flame ionisation detector at detection limits of - 0.2 fig (58). The nonvolatile amide was converted to the nitrile by reaction with heptafluorobutryic anhydride (56). For a related molecule, quinolinic acid, fmol detection limits were claimed for a gc procedure using either packed or capillary columns after derivatization to its hexafluoroisopropyl ester (58). 

Table 3. Nicotinic Acid and Nicotinamide (Vitamin B ) Content of Foodstuffs, mg/kg ...

Both nicotinic acid and nicotinamide have been used in the enrichment of bread, flour, and other grain-derived products. Animal feed is routinely supplemented with nicotinic acid and nicotinamide. Nicotinamide is also used in multivitamin preparations. Nicotinic acid is rarely used in this appHcation. The amide and carboxyHc acid have been used as a hrightener in electroplating baths and as stabili2er for pigmentation in cured meats. 

Niacin. Figure 1 Structure of nicotinic acid and nicotinamide. 

The detection limits for nicotinic acid and nicotinamide are 200 ng substance per chromatogram zone. 

Niacin was discovered as a nutrient during studies of pellagra. It is not strictly a vitamin since it can be synthesized in the body from the essential amino acid tryptophan. Two compounds, nicotinic acid and nicotinamide, have the biologic activity of niacin its metabolic function is as the nicotinamide ring of the coenzymes NAD and NADP in oxidation-reduction reactions (Figure 45-11). About 60 mg of tryptophan is equivalent to 1 mg of dietary niacin. The niacin content of foods is expressed as mg niacin equivalents = mg preformed niacin + 1/60 X mg tryptophan. Because most of the niacin in cereals is biologically unavailable, this is discounted. 

Figure 45-11. Niacin (nicotinic acid and nicotinamide) and nicotinamide adenine dinucieotide (NAD). Shows the site of phosphoryiation in NADP.

Nicotinic acid has been used to treat hyperlipidemia when of the order of 1—6 g/d are required, causing dilation of blood vessels and flushing, with skin irritation. Intakes of both nicotinic acid and nicotinamide in excess of 500 mg/d can cause liver damage. 

Chapter 10 is devoted to the preparation and purification of hydrophilic vitamins (C, Bj, Bj, Bg, B[2, nicotinic acid and nicotinamide, pantothenic acid, biotin, and folic acid) in pharmaceutical preparations, food products, and biological samples. 

A TLC method was developed for the estimation of nieotinie aeid and nicotinamide (Fignre 10.7) in phatmacentical preparations containing other vitamins, enzymes, herbs, and drugs, etc. [16]. The percentage recoveries for nicotinic acid and nicotinamide were 100.1 + 1.9 and 100.2 1.5, respectively, with this system. Each alcohol extract of samples or standard was pnt on sihca gel TLC plates, which were developed with distilled water. Each silica gel spot visualized under UV lamp was collected and extracted with 0.1 mol/1 HCl. The optical density of each clear extract was measured at 262 run. 

FIGURE 10.7 Structural formula of nicotinic acid and nicotinamide. 1 — nicotinic acid, 2 — nicoinamide. 

The range of nicotinic acid activity in blood, for a group of 28 normal subjects is 3.9-9.6 qg/ml. Only a fraction of less than 1% (0.016-0.05 pg/ml) of this quantity was present in serum. The range in urine was 1.16-1.54 pg/ml. Ninety-seven to 101% of added combinations of nicotinic acid and nicotinamide was recovered when added to blood and urine. In blood, appreciable nicotinic activity is observed only after... 

The reason for the absence of an additive response to nicotinic acid plus nicotinamide, seen with whole blood and in recovery experiments, remains obscure. Nicotinic acid and nicotinamide seem to interfere with each other s utilization. There may exist a competition between nicotinic acid and nicotinamide for methylation growth therefore would not reach an algebraic sum when the two are combined because of the limited number of methyl groups available for these compounds. 

H3. Handler, P., and Kohn, H. I., The mechanism of cozymase synthesis in the human erythrocyte a comparison of the role of nicotinic acid and nicotinamide. J. Biol. Chem. 150, 447-452 (1943). 

Evered DF, Sadoogh-Abasian F, Patel PD (1980) Absorption of nicotinic acid and nicotinamide across human buccal mucosa in vivo. Life Sci 27 1649-1651... 

Niacin is a generic name for a small family of molecules having niacin biological activity. The most common structures that fall into this category are nicotinic acid and nicotinamide ... 

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. ... 

Niacin, which refers to nicotinic acid and nicotinamide, is the metabolic precursor to three nicotinamide coenzymes. These are essential for the activity of a large number of enzymes catalyzing redox reactions. Pellagra is a niacin deficiency disease. 

Niacin the generic name for nicotinic acid and nicotinamide precursors for the coenzymes NAD+ and NADP+. 

C. L. Crowley, C. M. Payne, H. Bernstein, C. Bernstein and D. Roe, The NAD + precursors, nicotinic acid and nicotinamide protect cells against apoptosis induced by a multiple stress inducer, deoxycholate, Cell Death Differ., 2000, 7(3), 314. 

Nicotinic acid and nicotinamide are precursors of the coenzymes NAD+ and NADP+, which play a vital role in oxidation-reduction reactions (see Box 7.6), and are the most important electron carriers in intermediary metabolism (see Section 15.1.1). We shall look further at the chemistry of NAD+ and NADP+ shortly (see Box 11.2), but note that, in these compounds, nicotinamide is bound to the rest of the molecule as an A-pyridinium salt. 

Although nicotinic acid and nicotinamide function identically as vitamins, their pharmacologic effects differ. In large doses (up to 6 g/day), nicotinic acid is effective in reducing serum lipids (low-density lipoprotein [LDL], high-density lipoprotein [HDL], triglycerides, and lipoprotein A. Nicotinic acid produces vasodilation and increased blood flow due to histamine release. Nicotinamide does not affect blood lipid levels or the cardiovascular system. 

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. 

FIGURE 13-17 Structures of niacin (nicotinic acid) and its derivative nicotinamide. The biosynthetic precursor of these compounds is tryptophan. In the laboratory, nicotinic acid was first produced by oxidation of the natural product nicotine—thus the name. Both nicotinic acid and nicotinamide cure pellagra, but nicotine (from cigarettes or elsewhere) has no curative activity. 

Nicotinic acid and nicotinamide, members of the vitamin B group and used as additives for flour and bread enrichment, and as animal feed additive among other applications, are made to the extent of 24 million pounds (nearly 11 million kilograms) per year throughout the world. Nicotinic acid (pyridine-3-caiboxylic acid), also called niacin, has many uses. See also Niacin. Nicotinic acid is made by the oxidation of 3-picolme or 2-mcthyl-5-cthylpyridine (the isocinchomcnc acid produced is partially deearboxylated). Alternatively, quinoline (the intermediate quinolinic acid) is partially deearboxylated with sulfuric add in the presence of selenium dioxide at about 300° C or with nitric acid, or by electrochemical oxidation. Nicotinic acid also can be made from 3-picoline by catalytic ammoxidation to 3-cyanopyridine, followed by hydrolysis. 

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). 

Niacin is one of the more stable water-soluble vitamins. Both nicotinic acid and nicotinamide are stable in air at ambient temperature (93,96). Aqueous solutions of nicotinic acid or nicotinamide can be autoclaved for short periods, e.g., 10 minutes at 120°C, without degradation. Nicotinic acid s stability in solution is independent of pH, but nicotinamide is stable only at neutral pH. Heating nicotinamide in 1 N acid or alkali at 100°C will induce its conversion to nicotinic acid. 

Both nicotinic acid and nicotinamide are soluble in water, short-chain alcohols, and glycerol. Nicotinamide is sparingly soluble in diethyl ether nicotinic acid is insoluble. 

LV Hankes. Nicotinic acid and nicotinamide. In LJ Machlin, ed. Handbook of Vitamins. New York Marcel Dekker, 1984, pp 329-377. 

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