Animal niacin

The best-established function of poly(ADP-ribose) polymerase is in repair of damaged DNA it is activated by DNA strand breaks, and acts to clear histones and other nucleoproteins away from the DNA to permit access of the DNA repair enzymes. Both in vitro and in experimental animals, niacin deficiency leads to increased genomic instability, as the ability to repair damaged DNA is impaired, and may increase tumor risk. There is little information about genomic instability and cancer risk in human niacin deficiency (ffageman and Stiemm, 200f). 

Vitamin E, while not necessary for health, seems to be required for the reproduction and lactation of animals. Niacin, a member of the B group of vitamins, is necessary for the prevention of the deficiency disease pellagra. Pantothenic acid, inositol, />-aminobenzoic acid, and biotin are substances involved in the process of normtl growth. Vitamin K is a vitamin that prevents bleeding, by assisting in the process of dotting of the blood. 

Other Additives. Cats cannot convert tryptophan to niacin (22), or carotene to vitamin A in sufficient amounts to meet thein needs (23). These deviations, as compared with other animals, need not produce problems because added dietary sources of niacin and vitamin A provide the needs of cats. 

Most foods of animal origin contain nicotinamide in the coenzyme form (high bioavialability). Liver and meat are particularly rich in highly bioavailable niacin. Most of the niacin in plants, however, occurs as nicotinic acid in overall lower concentrations and with a lower bioavailability. The major portion of niacin in cereals is found in the outer layer and its bioavailability is as low as 30% because it is bound to protein (niacytin). If the diet contains a surplus of L-tryptophan (Ttp), e.g., more than is necessary for protein synthesis, the liver can synthesize NAD from Trp. Niacin requirements are therefore declared as niacin equivalents (1 NE = 1 mg niacin = 60 mg Trp). 

With well-established animal models to evaluate vasodilation and FFA reduction, several compounds were profiled in vivo and they indeed displayed improved TIs relative to niacin. Furthermore, these models appeared to correlate to humans as two candidates including both... 

That individual monkeys have distinctive niacin needs was shown by recent work of Tappan and co-workers.59 One animal, for example, required only 11 weeks to show niacin deficiency weight loss by this animal was halted only when 30 mg. of niacin was given. Another animal required 9 months to show a niacin deficiency and then grew adequately when only 6 mg. of niacin per week was furnished. This seems to show a several-fold range in niacin needs within a small group of fine animals. The tryptophane needs of the different monkeys, as judged by growth responses, were found to vary under comparable conditions from 1 to about 3.5 gm. per week. 

Nicotinate and nicotinamide, together referred to as niacin, are required for biosynthesis of the coenzymes nicotinamide adenine dinucleotide (NAD"") and nicotinamide adenine dinucleotide phosphate (NADP" ). These both serve in energy and nutrient metabolism as carriers of hydride ions (see pp. 32, 104). The animal organism is able to convert tryptophan into nicotinate, but only with a poor yield. Vitamin deficiency therefore only occurs when nicotinate, nicotinamide, and tryptophan are all simultaneously are lacking in the diet. It manifests in the form of skin damage (pellagra), digestive disturbances, and depression. 

Precursors in the biosynthesis of niacin In animals and bacteria, tryptophan and in plants, glycerol and succinic acid. Intermediates in the synthesis include kynurenine, hydroxyanthranilic acid, and quinolinic acid. In animals, the niacin storage sites are liver, heart, and muscle. Niacin supplements are prepared commercially by (1) Hydrolysis of 3-cyanopyndine or (2) oxidation of nicotine, quinoltne, or collidine. 

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. 

There are exceptions to the above. Most or all vitamins can be synthesized chemically. Vitamin D can be synthesized in the skin of animals by exposure to ultraviolet irradiation, and nicotinic acid (niacin) can be synthesized in the body from the AA tryptophan. 

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. 

The human requirement of niacin is related to the intake of tryptophan. Animal proteins contain approximately 1.4 percent of tryptophan, vegetable proteins about 1 percent. A dietary intake of 60 mg of tryptophan is considered equivalent to 1 mg of niacin. When this is taken into account, average diets in the United States supply 500 to 1,000 mg tryptophan per day and 8 to 17 mg niacin for a total niacin equivalent of 16 to 33 mg. The RDA for adults, expressed as niacin, is 6.6 mg per 1,000 kcal, and not less than 13 mg when caloric intake is less than 2,000 kcal. 

Good dietary sources of this vitamin are liver, kidney, lean meat, chicken, fish, wheat, barley, rye, green peas, yeast, peanuts, and leafy vegetables. In animal tissues, the predominant form of niacin is the amide. Niacin content of some foods are listed in Table 9-22. 

Niacin is present in tissues, and therefore in foods, iargeiy as the nicotinamide nucleotides. The postmortem hydrolysis of NAD(P) is extremely rapid in animal tissues, and it is likely that much of the niacin of meat (a major dietary source of the vitamin) is free nicotinamide. 

In the liver, there is litde utilization of preformed niacin for nucleotide synthesis. Although isolated hepatocytes will take up both vitamers from the incubation medium, they seem not to be used for NAD synthesis and cannot prevent the fall in intracellular NAD(P), which occurs during incubation. The enzymes for nicotinic acid and nicotinamide utilization are more or less saturated with their substrates at normal concentrations in the liver, and hence are unlikely to be able to use additional niacin for nucleotide synthesis. By contrast, incubation of isolated hepatocytes with tryptophan results in a considerable increase in the rate of synthesis of NAD(P) and accumulation of nicotinamide and nicotinic acid in the incubation medium. Similarly, feeding experimental animals on diets providing high intakes of nicotinic acid or nicotinamide has relatively little effect on the concentration of NAD (P) in the liver, whereas high intakes of tryptophan lead to a considerable increase. It thus seems likely that the major role of the liver is to synthesize NAD(P) from tryptophan, followed by hydrolysis to release niacin for use by extrahepatic tissues (Bender et al., 1982 McCreanor and Bender, 1986 Bender and Olufunwa, 1988). 

Kynurenine Hydroxylase Kynurenine hydroxylase is an FAD-dependent mixed-function oxidase of the outer mitochondrial membrane, which uses NADPH as the reductant. The activity of kynurenine hydroxylase in the liver of riboflavin-deficient rats is only 30% to 50% of that in control animals, and deficient rats excrete abnormally large amounts of kynurenic and anthranilic acids after the administration of a loading dose of tryptophan, and, correspondingly lower amounts of quinolinate and niacin metabolites. Riboflavin deficiency may thus be a contributory factor in the etiology of pellagra when intakes of tryptophan and niacin are marginal (Section 8.5.1). 

Measurement of liver and other tissue concentrations of NAD(P) gives a precise estimate of niacin nutritional status and seems to be the most sensitive indicator in experimental animals. Measurement of the whole blood concentration of NAD (P) may serve the same purpose there is a good correlation between blood and liver concentrations of nicotinamide nucleotides in experimental animals. The sensitivity of the method is such that reproducible determinations can be carried out on finger-prick samples of 200 /xL of blood (Bender etal., 1982). 

Animals and yeasts can synthesize nicotinamide from tryptophan via hydroxyanthranilic acid (52) and quinolinic acid (53, Fig. 6A) (31), but the biosynthetic capacity of humans is limited. On a diet that is low in tryptophan, the combined contributions of endogenous synthesis and nutritional supply of precursors, such as nicotinic acid, nicotinamide, and nicotinamide riboside, may be insufficient, which results in cutaneous manifestation of niacin deficiency under the clinical picture of pellagra. Exogenous supply of nicotinamide riboside was shown to promote NAD+-dependent Sir2-function and to extend life-span in yeast without calorie restriction (32). 

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