Tryptophan Nicotinic acid

B19. Banerjee, S., and Agarival, P. S., Nicotinic acid-tryptophan metabolism in certain diseases. Proc. Soc. Exptl. Biol. Med. 97, 65-68 (1958). 

Entrapment of nicotinic acid, tryptophan, picol-inic acid, and 6-aminohexanoate into poly-[Ru(v-bpy)3l coatings on platinum microelectrodes Mercury [24]... 

There are isolated cases of apparent interactions between clozapine, and ampicillin, buspirone, caffeine, haloperidol, loperamide, modafinil, nefazodone, nicotinic acid, tryptophan, or vitamin C. Grapefruit juice, influenza vaccine mirtazapine, reboxetine, or venlafaxine do not appear to interact Cocaine levels may increase when taken with clozapine. 

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. 

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). 

The biosynthesis and metabolism of nicotinic acid in disease has received little attention metabolic studies deal mainly with normal animals and man (01, R5). After a tryptophan load dose, the main catabolites in the urine are nicotinuric acid, N1-methylnicotinamide, nicotinamide, quinolinic acid, kynurenine, 6-pyridone, anthranilic acid, and 3-hydroxyanthranilic acid. These excretory products were estimated... 

Vitamin Ba (pyridoxine, pyridoxal, pyridoxamine) like nicotinic acid is a pyridine derivative. Its phosphorylated form is the coenzyme in enzymes that decarboxylate amino acids, e.g., tyrosine, arginine, glycine, glutamic acid, and dihydroxyphenylalanine. Vitamin B participates as coenzyme in various transaminations. It also functions in the conversion of tryptophan to nicotinic acid and amide. It is generally concerned with protein metabolism, e.g., the vitamin B8 requirement is increased in rats during increased protein intake. Vitamin B6 is also involved in the formation of unsaturated fatty acids. 

Epileptiform fits associated with degenerative changes in the myelin sheath of peripheral nerves and spinal cord occur in B6-deficient animals. Lesions in the arteries, resembling those of human atherosclerosis, have been observed in Be-deficient monkeys. Recently, a state of Be deficiency in human infants, characterized by loss of ability to convert tryptophan to nicotinic acid, by impaired growth, convulsions, and hypochromic anemia, has been described, following omission of vitamin B6 from the diet. 

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. 

Alkaloids derived from nicotinic acid contain a pyridine nucleus. Nicotinic acid itself is synthesized from L-tryptophan via A-formylkynurenine, L-kynurenine, 3-hydroxykynurenine, 3-hydroxyanthranilic acid and quinolinic acid. 

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. 

Vitamins must be derived from the diet because either they cannot be synthesized de novo in human beings or their rate of synthesis, e.g. the production of nicotinic acid from tryptophan, is inadequate for the maintenance of health. Only vitamin D can be manufactured by the body at a sufficient rate. 

Drug-induced niacin deficiency has resulted from the use of isonicotinic acid hydrazide, which interferes with the conversion of niacin from tryptophan. Administration of ethanol or the antimetabolites 6-mercaptop-urine and 5-fluorouracil also may lead to niacin deficiency. The uricosuric effects of sulfinpyrazone and probenecid may be inhibited by nicotinic acid. 

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. 

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. 

Niacin is found in unrefined and enriched grains and cereal, milk, aid lean meats, especially liver. Limited quantities of niacin can also be obtained from the metabolism of tryptophan. [Note The pathway is inefficient in that only about 1 mg of nicotinic acid is formed from 60 mg of tryptophan. Further, tryptophan is metabolized to niacin orty when there is a relative abundance of the amino acid—that is, alter the needs for protein synthesis and energy production have been met]... 

The daily requirement for an adult is about 7.5 mg. The amount is decreased by the presence in the diet of tryptophan, which can be converted partially to nicotinic acid (Chapter 25).d e Tryptophan is about 1 /60 as active as nicotinic acid itself. The one-time prevalence of pellagra in the southern United States was a direct consequence of a diet high in maize whose proteins have an unusually low tryptophan content. 

Tryptophan is a metabolic precursor for many important biochemical compounds, such as nicotinic acid, kynurenic acid, serotonin, and melatonin (67). The tryptophan content of various food-... 

Humans can convert ingested tryptophan to niacin in vivo (19,93,96). Therefore, the niacin activity of food can be expressed in niacin equivalents, which is the sum of the niacin content (nicotinic acid vitamers + nicotinamide vitamers) plus 1/60 of the tryptophan content (in mg). This section will be restricted to analyses for the niacin vitamers. Tryptophan methodology will not be covered. 

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. 

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