Tryptophan niacin synthesized from

NAD(H) from niacin (some may be synthesized from tryptophan)... 

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. 

Niacin and riboflavin are converted to their respective coenzymes, NAD+ and NADP+ on the one hand and flavin munonucleotide (FMN) and flavin adenine dinucleotide (FAD) on the other, as described in Chapter 10. Some NAD+ can be synthesized from tryptophan, as described in Chapter 20. Tryptophan, however, provides only a fraction of our daily NAD+ requirements. 

Niacin and niacinamide refer to nicotinic acid and its amide. Nicotinic acid is a pyridine derivative synthesized from tryptophan. 

Nicotinate (also called niacin or vitamin Bg) is derived from tryptophan. Human beings can synthesize the required amount of nicotinate if the supply of tryptophan in the diet is adequate. However, nicotinate must be obtained directly if the dietary intake of tryptophan is low. A dietary deficiency of tryptophan and nicotinate can lead to pellagra, a disease characterized by dermatitis, diarrhea, and dementia. An endocrine tumor that consumes large amounts of tryptophan in synthesizing the hormone and neurotransmitter serotonin (5-hydroxytryptamine) can lead to pellagralike symptoms. 

One of the substances commonly treated as a vitamin is niacin, which is synthesized from the essential amino acid tryptophan. The ratio is approximately 60 mg of tryptophan being required to produce 1 mg of niacin (1). This has led to niacin requirements being expressed as niacin equivalents (NE), based on the amount of tryptophan in the diet. It must be kept in mind that tryptophan is essential and is the precursor to the neurotransmitter serotonin in addition to being part of protein structure. Therefore, niacin can be thought of as tryptophan sparing. 

Nicotinic acid (niacin) is a precursor of nicotinamide adenine dinucleotide (NAD) which plays a central role in metabolism as a coenzyme. It can be synthesized from tryptophan. Tryptophan and nicotinate deficiency lead to pellagra, which is characterized by diarrhea, dermatitis, and dementia. Maize-rich diets... 

Vitamins, by definition, cannot be synthesized in the body, or are synthesized from a very specific dietary precursor in insufficient amounts. For example, we can synthesize the vitamin niacin from the essential amino acid tryptophan, but not in sufficient quantities to meet our needs. Niacin is therefore still classified as a vitamin. 

Our species has lost the ability to make vitamins. Thus, deficiency of niacin (nicotinamide), the N in NAD, leads to the disease pellagra, a collection of skin, intestinal, and neurological symptoms. (Niacin can be synthesized from the amino acid tryptophan, so pellagra results from a deficiency of both niacin and tryptophan in the diet.)... 

The definition of a vitamin has been extended by some (Spector, 1980) to Include those chemical compounds required by a specific tissue but not synthesized by that tissue. For example. In certain species, vitamin C can be synthesized from glucose In the liver but not In the Central Nervous System therefore, vitamin C Is not considered a vitamin for these animals. Vitamin C for the brain must be drawn from the blood, from the vitamin C that entered the blood from the diet, or was synthesized In the liver. Subsequently, vitamin C could be considered a vitamin for the brain since It must be obtained from outside the brain. Another example Is the vitamin niacin, which cannot be synthesized from tryptophane In mammalian brain however, the synthesis of niacin from tryptophane occurs In mammalian liver (Spector and Kelly, 197.9 Spector, 1979). 

As shown in Figure 11.13, the nicotinamide nucleotide coenzymes can be synthesized from either of the niacin vitamers, and from quinolinic acid, an intermediate in the metabolism of tryptophan. In the liver, the oxidation of tryptophan results in a considerably greater synthesis of NAD than is required, and this is catabolized to release nicotinic acid and nicotinamide, which are taken up and used by other tissues for synthesis of the coenzymes. 

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). 

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. 

A number of genetic diseases that result in defects of tryptophan metabolism are associated with the development of pellagra despite an apparently adequate intake of both tryptophan and niacin. Hartnup disease is a rare genetic condition in which there is a defect of the membrane transport mechanism for tryptophan, resulting in large losses due to intestinal malabsorption and failure of the renal resorption mechanism. In carcinoid syndrome there is metastasis of a primary liver tumor of enterochromaffin cells which synthesize 5-hydroxy-tryptamine. Overproduction of 5-hydroxytryptamine may account for as much as 60% of the body s tryptophan metabolism, causing pellagra because of the diversion away from NAD synthesis. 

In contrast to most of the vitamins encountered so far, here we have simple structures. Humans are able to synthesize these molecules from the amino acid tryptophan but not in quantities adequate to meet physiological needs. Consequently, we need to find adequate amounts in our diet. The UL for niacin is 35 mg/day for adult men and women. 

A deficiency of niacin in the diet results in the disease known as pellagra, characterized by the four D s diarrhea, dermatitis, dementia, and death. In the early years of the twentieth century in the United States, pellagra was common among poor tenant farmers and mill workers in the rural South. The diet there at that time was rich in com that contained little niacin and little available tryptophan from which to synthesize it. 

Niacin, a water-soluble vitamin vital for oxidation by living cells, functions in the body as a component of two important coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). NAD and NADP are involved in the release of energy from carbohydrate, fat, and protein, and in the synthesis of protein, fat, and pentoses for nucleic acid formation. Milk is a poor source of preformed niacin, containing about 0.08 mg per 100 g. However, milk s niacin value is considerably greater than indicated by its niacin content (Horwitt et al. 1981). Not only is the niacin in milk fully available, but the amino acid tryptophan in milk can be used by the body for the synthesis of niacin. For every 60 mg of tryptophan consumed, the body synthesizes 1 mg of niacin. Therefore, the niacin equivalents in 100 g milk equal 0.856 mg including that from pre-... 

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. 

It is not strictly correct to regard niacin as a vitamin. Its metabolic role is as the precursor of the nicotinamide moiety of the nicotinamide nucleotide coenzymes, nicotinamide adenine dinucleotide (NAD) and NADP, and this can also be synthesized in vivo from the essential amino acid tryptophan. At least in developed countries, average intakes of protein provide more than enough tryptophan to meet requirements for NAD synthesis without any need for preformed niacin. It is only when tryptophan metabolism is disturbed, or intake of the amino acid is inadequate, that niacin becomes a dietary essential. 

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). 

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). 

Niacin is not a true vitamin in the strictest definition since it can be derived from the amino acid tryptophan. However, the ability to utilize tryptophan for niacin synthesis is inefficient (60 mg of tryptophan are required to synthesize 1 mg of niacin). Also, synthesis of niacin from tryptophan requires vitamins Bi, B2 and Bg, which would be limiting in them on a marginal diet. 

Ethanol Oxidation Is Schematically Illustrated Below As noted above, nicotinic acid (also known as niacin to avoid confusion with nicotine) can be made available in nucleotide form from the amino acid tryptophan. It has been estimated that a dosage of 60 mg of tryptophan equals that of I mg of nicotinic acid. Consequently, humans and other mammals can synthesize the vitamin, provided there is appropriate dietary availability of tryptophan. (Thus, nicotinic... 

E. Although niacin is a vitamin, it may be synthesized to a limited extent from tryptophan. The other compounds are required in the diet. 

Certain vitamins can be synthesized by humans in limited quantities. Niacin can be formed from tryptophan (Chapter 17). This pathway is not active enough to satisfy all the body s needs however, in calculating the RDA for niacin, 60 mg of dietary tryptophan is considered equivalent to 1 mg of dietary niacin. In Hartnup s disease (see Table 38-1 and Chapter 17), a rare hereditary disorder in the transport of monoaminomonocarboxylic acids (e.g., tryptophan), a pellagra-like rash may appear, suggesting that over a long period of time dietary intake of niacin is insufficient for metabolic needs. This pattern also occurs in carcinoid syndrome in which much tryptophan is shunted into the synthesis of 5-hydroxytryptamine. 

Niacin (nicotinic acid pyridine-3-carboxylic acid) and nicotinamide are precursors of NAD+ and NADP+ (Figure 38-19). Niacin occurs in meat, eggs, yeast, and whole-grain cereals in conjunction with other members of the vitamin B group. Little is known about absorption, transport, and excretion of niacin and its coenzyme forms. A limited amount of niacin can be synthesized in the body from tryptophan, but it is not adequate to meet metabolic needs. 

Nicotinamide is derived from nicotinic acid that is synthesized by human cells from the essential amino acid tryptophan. Our diet is also a rich source of nicotinamide, so the body has adapted to synthesizing much less than the daily requirements. Many commercial breakfast cereals and spreads are supplemented with nicotinamide that is usually termed niacin or vitamin B3 on their Nutrition Fact labels. 

The status of niacin in relation to most other vitamins is different as it can be synthesized by humans to some extend from tryptophan. Body status determination has been based on the determination of urinary excretion of niacin metabolites, predominately N-methyl-2-pyridone-5-carboxylamide and N-methyl-nicotinamide. The ratio of these compounds has been used as indicator of niacin status. Recent studies suggest that the determination of the two niacin-derived coenzymes, NAD and NADP, in erythrocytes, and their ratio are more reliable indicators of niacin status. However, a broadly accepted and easy to use determination method does not seem to exist. 

In the organism that Is required In small amounts In food to sustain the normal metabolic functions of life. The key to this definition Is that this chemical compound must be supplied to the organism because the animal cannot synthesize vitamins. Lack of It produces a specific deficiency syndrome and supplying It cures that deficiency. An exception to this definition Is vitamin D, which can be made In the skin upon adequate exposure to sunlight. However, without adequate exposure, the animal Is dependent on a dietary source. Biotin, panthothenlc acid, and vitamin R are made by bacteria In the human Intestine, based on a symbiotic relation-ship and, thus, are not required by the human. Niacin can also be synthesized In humans from the amino acid tryptophane. 

Nicotinamide can be formed by animal cells from tryptophan but is usually present in the diet. Starting from ribose-l-phosphate and niacin (nicotinamide), DPN is probably synthesized as shown in Fig. 76. TPN results from the phosphorylation of DPN in the presence of a specific phosphokinase. TPN can be converted to DPN by a phosphatase. 

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