Tryptophan intake

Plasma tryptophan concentration is a function of dietary tryptophan intake as well as the extent of removal of tryptophan from blood by tissues. The liver is the main organ influencing plasma tryptophan concentration since it actively metabolizes tryptophan while nonhepatic tissues have only relatively limited ability to act in this manner. Following a meal, in the liver, tryptophan stimulates hepatic tryptophan oxygenase activity, which affects tryptophan catabolism and determines how much tryptophan enters the general circulation. 

It seems probable that the wasting in AIDS patients is due at least in part to a chronic depletion of tryptophan. Although in AIDS patients blood tryptophan levels are low, other amino acids are not reduced to the same extent.28 This pattern is similar to that found in pellagra due to poor tryptophan intake.29 Nutrition and anthropometric studies on AIDS patients indicate that protein is lost but fat is little changed. Administration of excessive dietary tryptophan may relieve the tryptophan deficiency but may increase quinolinic acid levels, which would likely worsen the AIDS dementia. Conceivably, a better approach to improve tryptophan levels would be to utilize inhibitors of IDO, which would also decrease the levels of quinolinic acid. Such approaches with inhibitors of IDO in vitro have been investigated.30-33... 

The role that melatonin may play as a consequence of tryptophan intake in sleep merits consideration. Improvement in sleep latency, increasing sleep efficiency, and raising sleep quality scores in elderly, melatonin-deficient insomniacs occur with low doses of melatonin. 

Some studies have attempted to evaluate whether the levels of L-tryptophan intake would be of importance. Increasing dosage of implicated L-tryptophan did seem to influence the severity of EMS. 

Whether very high levels of L-tryptophan intake may be toxic to humans is not known. However, in animal studies, ingestion of high levels of nonim-plicated L-tryptophan can be lethal. The LDS0 level of L-tryptophan for rats is 1.62 g/kg.117 Similar levels are effective in mice and rabbits. Guidelines for the upper limits of L-tryptophan ingestion in humans need to be established. 

Although nicotinamide is a vitamin, it can also be synthesized from tryptophan. Therefore, the NAD levels of the organism depend on both nicotinamide and tryptophan intake. The pathway of NAD biosynthesis starting from tryptophan is discussed in detail later. NADP is much less abundant in the cell than NAD. The biosynthesis of NADP probably involves the reaction of NAD with ATP in the presence of a nucleotide pyrophosphorylase. 

From the role of tryptophan in the biosynthesis of nicotinic acid, it is obvious that the nutritional studies on nicotinic acid deficiency must take tryptophan intake into account. Indeed, 60 mg of tryptophan in the diet is as effective as 1 mg of nicotinic acid. Since 70 g of protein yields 720 mg of tryptophan, the intake of such an amount of protein corresponds to 12 mg of nicotinic acid in preventing niacin deficiency. Since the requirements for niacin, like those of thiamine, depend essentially on the caloric intake, it is useful to express the requirements in niacin equivalents per 1000 calories. The optimum requirement is 4.4 mg niacin per 1000 calories. 

The requirement for preformed niacin tends to be lower with higher tryptophan intakes, while the requirement for preformed niacin is increased by factors that reduce the conversion of tryptophan to niacin. These factors include low tryptophan intake and inadequate iron, riboflavin or vitamin Bg status, which participate in the conversion of tryptophan to niacin (Food and Nutrition Board 1998). Other cases of reduced conversion of tryptophan to niacin are... 

The daily requirement (cf. Table 6.3) is covered to an extent of 60-70% by tryptophan intake. Hence, milk and eggs, though they contain little niacin, are good foods for prevention of pellagra because they contain tryptophan. It substitutes for niacin in the body, with 60 mg L-tryptophan equalling I mg nicotinamide. Indicators of sufficient supply of niacin in the diet are the levels of metabolites II (cf. Formula 6.13) in urine or III and IV in blood plasma. 

The RDA for niacin is based on the concept that niacin coen2ymes participate in respiratory en2yme function and 6.6 niacin equivalents (NE) are needed per intake of 239 kj (1000 kcal). One NE is equivalent to 1 mg of niacin. Signs of niacin deficiency have been observed when less than 4.9 NE/239 kj or less than 8.8 NE per day were consumed. Dietary tryptophan is a rich source of niacin and the average diet in the United States contains 500—1000 mg of tryptophan. In addition, the average diet contains approximately 8—17 mg of niacin. In total, these two quantities total 16—34 NE daily. Table 5 Hsts the RDA and U.S. RDA for niacin (69). 

All 20 of the amino acids present in proteins are essential for health. While comparatively rare in the Western world, amino acid deficiency states are endemic in certain regions of West Africa where the diet relies heavily on grains that are poor sources of amino acids such as tryptophan and lysine. These disorders include kwashiorkor, which results when a child is weaned onto a starchy diet poor in protein and marasmus, in which both caloric intake and specific amino acids are deficient. 

Not all proteins are nutritionally equivalent. Mote of some than of others is needed to maintain nittogen balance because different proteins contain different amounts of the various amino acids. The body s requirement is for specific amino acids in the correct proportions to replace the body proteins. The amino acids can be divided into two groups essential and nonessential. There are nine essential or indispensable amino acids, which cannot be synthesized in the body histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine. If one of these is lacking or inadequate, then—regardless of the total intake of protein—it will not be possible to maintain nitrogen balance since there will not be enough of that amino acid for protein synthesis. 

Pellagra Can Occur as a Result of Disease Despite an Adequate Intake of Tryptophan Niacin... 

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. 

Heger J, Van Phung T and Krizova L (2002), Efficiency of amino acid utilization in the growing pig at suboptimal levels of intake lysine, threonine, sulphur amino acids and tryptophan , J Anim Physiol An N, 86, 153-165. 

The amino acid L-tryptophan is the precursor for the synthesis of 5-HT. The synthesis and primary metabolic pathways of 5-HT are shown in Figure 13-5. The initial step in the synthesis of serotonin is the facilitated transport of the amino acid L-tryptophan from blood into brain. The primary source of tryptophan is dietary protein. Other neutral amino acids, such as phenylalanine, leucine and methionine, are transported by the same carrier into the brain. Therefore, the entry of tryptophan into brain is not only related to its concentration in blood but is also a function of its concentration in relation to the concentrations of other neutral amino acids. Consequently, lowering the dietary intake of tryptophan while raising the intake of the amino acids with which it competes for transport into brain lowers the content of 5-HT in brain and changes certain behaviors associated with 5-HT function. This strategy for lowering the brain content of 5-HT has been used clinically to evaluate the importance of brain 5-HT in the mechanism of action of psychotherapeutic drugs. 

Serotonergic neurons contain the enzyme L-tryptophan-5-monooxygenase (EC 1.14.16.4), more commonly termed tryptophan hydroxylase, which converts tryptophan to 5-hydroxytryptophan (5-HTP) (Fig. 13-5). Tryptophan hydroxylase contains 444 amino acids, corresponding to a molecular weight of about 51 Da. This enzyme is synthesized in serotonergic cell bodies of the raphe nuclei and is found only in cells that synthesize 5-HT. Therefore its distribution in brain is similar to that of 5-HT itself. The Km of tryptophan hydroxylase for tryptophan is approximately 30-60 pmol/1, a concentration comparable to that of tryptophan in brain. If the concentration of tryptophan in serotonergic neurons is assumed to be comparable to that in whole brain, the enzyme would not be saturated with substrate, and the formation of 5-HT in brain would be expected to rise as the brain concentration of tryptophan increases. This has been found to occur in response to raising the dietary intake of tryptophan specifically. 

Because AADC is not saturated with 5-HTP under physiological conditions, (i.e. the concentration of 5-HTP is much less than the enzyme s Km of 10pmol/l), it is possible to raise the content of 5-HT in brain not only by increasing the dietary intake of tryptophan but also by raising the intake of 5-HTP. This procedure, though,... 

Treatment of aminoacidurias with a low-protein diet may influence brain chemistry. It should be emphasized that the treatment of the patient with an aminoaciduria may affect brain chemistry, perhaps in an adverse manner. Nearly all patients receive a low-protein diet. Indeed, undiagnosed patients sometimes avoid consumption of protein, which they feel intuitively can cause lethargy, headache, nausea and mental confusion. As dietary protein declines, the intake of carbohydrate frequently increases. The concomitant rise of endogenous insulin secretion favors an increase in the ratio of the concentration of blood tryptophan to that of other amino acids, thereby promoting the entry of tryptophan to the brain. The latter amino acid is precursor to brain serotonin, which tends to increase. This physiology is known to be operative in patients with urea cycle defects. 

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. 

The amount of vitamin B6 required by humans is not well established,73 and only recently has evidence been obtained that the needs are variable. Hansen and Bessey74 have found that in some babies 3 or 4 times as much vitamin B6 is needed to prevent the excretion of xanthurenic acid after a test dose of tryptophane than in others. It is these particular babies who develop clinical vitamin B6 deficiency when the intake is low. These findings seem to indicate strongly that some babies have vitamin B6 requirements 3 or 4 times as high as others. 

L-tryptophane is the precursor of serotonin and other biological substances like tryptamine, kynure-nine and quinolinic acid. Furthermore, it is an essential substrate in the protein synthesis. The dietary intake of L-tryptophane might increase the production of serotonin. For this reason the aminoacid is used for the therapy of light sleeping disorders. 

The RDA for niacin is expressed in terms of energy intake 6.6 mg niacin equivalent (NE, 1 mg niacin or 60 mg tryptophan) per 1000 kcal (4186 kJ) per day is recommended (13NEday-1 minimum). This is approximately equivalent to 19 and 15 mg NE day -1 for men and women, respectively. The UK RNI value for niacin is 6.6 mg NE per 1000 kcal (4186 kJ) per day for adults. The richest dietary sources of niacin are meat, poultry, fish and whole-grain cereals. 

This value includes niacin equivalents from preformed niacin and from tryptophan. A dietary intake of 60 mg tryptophan is considered equivalent to 1 mg niacin. One niacin equivalent is equal to either to those amounts. 

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