Tryptophan excretion

A decrease in circulating tryptophan levels may be of importance in some models of hypertension. The DS rat is an example of this. The reduction in plasma tryptophan was clearly associated with the excess intake of NaCl and concomitant elevation in blood pressure. Mechanisms that could account for the reduction in plasma tryptophan could include a decrease in gastrointestinal absorption of tryptophan, an increase in urinary tryptophan excretion, increased oxidation of tryptophan by tryptophan oxygenase, and aberrant regulation (hormonal, nutrient, plasma protein) of tryptophan... 

In the metabolism of the aromatic amino acid tryptophan in mammals, two pathways for the formation of pyridine nucleotide coenzyme and in-doleamines are initiated by two well-known oxygenases, tryptophan 2,3-dioxygenase and tryptophan-5-hydroxylase (monooxygenase) (Fig. 2). Kotake and Ito (5) found in 1937 that rabbits fed D-tryptophan excreted D-kynurenine in the urine. Although the tryptophan-cleaving activity in... 

Many microorganisms can synthesise amino acids from inorganic nitrogen compounds. The rate and amount of some amino acids may exceed the cells need for protein synthesis, where the excess amino acids are excreted into the media. Some microorganisms are capable of producing certain amino acids such as lysine, glutamic acid and tryptophan. 

Various minor hematological effects have been noted in animals. Rats exposed to 50-800 ppm of trichloroethylene continuously for 48 or 240 hours showed time- and dose-related depression of delta-aminolevulinate dehydratase activity in liver, bone marrow, and erythrocytes (Fujita et al. 1984 Koizumi et al. 1984). Related effects included increased delta-aminolevulinic acid (ALA) synthetase activity, reduced heme saturation of tryptophan pyrrolase and reduced cytochrome P-450 levels in the liver and increased urinary excretion of... 

Phenoxazines — The microbial phenoxazines like actinomycins are well-known antibiotics. Actinomycin D produced by Streptomyces anibioticus is an effective antineoplastic agent that inhibits nucleic acid synthesis. The main function of ommochromes is to act as screening pigments in the eyes of insects and other arthropods, as pattern pigments in the integument, and as excretion products of excess tryptophan. ... 

Cl. Gassmann, B., Knapp, A., and Gartner, L. L., Vitamin Be deficiency and urinary excretion of xanthurenic acid and other tryptophan metabolites in disease. Klin. Wochschr. 37, 189-195 (1959). 

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. 

Patients show signs of tryptophan deficiency despite a healthy diet as well as elevated urinary and fecal excretion of the neutral amino acids. 

Returning to the major tryptophan catabolic pathway, marked by green arrows in Fig. 25-11, formate is removed hydrolytically (step c) from the product of tryptophan dioxygenase action to form kynurenine, a compound that is acted upon by a number of enzymes. Kynureninase (Eq. 14-35) cleaves the compound to anthranilate and alanine (step d), while transamination leads to the cyclic kynurenic acid (step e). Hie latter is dehydroxylated in an unusual reaction to quinaldic acid, a prominent urinary excretion product. 

A certain bacteria that was a tryptophan auxotroph was observed to grow well when it was supplied with tryptophan, but as soon as the tryptophan in the environment was exhausted it started to excrete a metabolite on the tryptophan biosynthetic pathway. Why didn t it excrete the metabolite before it exhausted the environmental tryptophan ... 

The same logic was used to identify the groups of mutants who allowed the growth of other mutants, or who were able to grow on the compounds excreted by other groups of mutants. In the case of tryptophan, five such complementation groups existed. 

Nutritional Effects Due to the Presence of the Maillard Products. Many physiological or antinutritional effects have been attributed to the Maillard products. Specific effects have been attributed to the Amadori products deoxyfructosylphenylalanine (a model substance not likely to be present in large quantities in foods) appears to depress the rate of protein synthesis in chicks (32) and to partially inhibit in vitro and in vivo the absorption of tryptophan in rats (33). The compound e-deoxyfructosyllysine inhibits the intestinal absorption of threonine, proline, and glycine and induces cytomegaly of the tubular cells of the rat kidneys (34) as does lysinoalanine. In parenteral nutrition the infusion of the various Amadori compounds formed during sterilization of the amino acid mixture with glucose is associated with milk dehydration in infants and excessive excretion of zinc and other trace metals in both infants and adults (35,36,37). 

Metabolic Transit. Free Amadori Compounds. It is well known that the synthetic Amadori compounds of the free amino acids are absorbed by the intestine and excreted unchanged in the urine (9,28,30). The transport is not active as observed with deoxyfructosyltryptophan (30) and c-deoxyfructosyllysine (40), and the level of absorption depends on the nature of the amino acid and on the conditions of ingestion. Nutritional assays and metabolic transit studies performed with radioactive Amadori compounds of tryptophan (12,30), leucine (12), and lysine (9,28,41) given orally or intravenously on normal or anti-biotics-treated animals have shown that the intestinal microflora can regenerate part of the amino acid. This can be absorbed subsequently at a very low level by the caecum or the large intestine and incorporated into the tissue proteins or utilized by the intestinal microflora. Barbiroli (13) showed also that some intestinal enzymes were able to liberate some amino acids from their Amadori compounds but to a very small... 

Tryptophan catabolism is also associated with several dead-end pathways, for example the formation of kynurenic and xanthurenic acids. Normal urine contains small amounts of hydroxykynurenine, kynurenine, kynurenic acid, and xanthurenic add. When large amounts of tryptophan are fed to animals, the excretion of these compounds increases. Xanthurenic acid is excreted in massive quantities in vitamin B6 deficiency. 

As shown in Figure 8.2, NAD(P) can be synthesized from the tryptophan metaboUte quinolinic acid. The oxidative pathway of tryptophan metabolism is shown in Figure 8.4. Under normal conditions, almost aU of the dietary intake of tryptophan, apart from the small amount that is used for net new protein synthesis, is metabolized by this pathway, and hence is potentially available for NAD synthesis. About 1% of tryptophan metabolism is by way of 5-hydroxylation and decarboxylation to 5-hydroxytryptarnine (serotonin), which is excreted mainly as 5-hydroxyindoleacetic acid. 

A number of studies have investigated the equivalence of dietary tryptophan and preformed niacin as precursors of the nicotinamide nucleotides, generally by determining the excretion of -methyl nicotinamide and methyl pyridone carboxamide in response to test doses of the precursors, in subjects maintained on deficient diets. 

Tryptophan dioxygenase (Section 8.3.2) is only found in the liver other tissues have an indoleamine dioxygenase, with lower specificity, that catalyzes the same reaction. However, the pathway for onward metabolism of kynure-nine is found only in liver and mononuclear phagocytes, and induction of indoleamine dioxygenase by cytokines, such as interferon-y, leads to increased circulating concentrations and urinary excretion of kynurenine, with litde or... 

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). 

The depletion/repletion studies of Horwitt et al. (1956) and others have suggested, on the basis of restoration of urinary excretion of -methyl nicotinamide, that the average niacin requirement is 5.5 mg per 1,000 kcal (1.3 mg per MJ). Allowing for individual variation, reference intakes (see Table 8.2) are set at 6.6 mg niacin equivalents (preformed niacin - -1 /60 of the dietary tryptophan) per 1,000 kcal (1.6 mgper MJ). Even when energy intakes are very low, it must be assumed that energy expenditure will not fall below 2,000 kcal, and this is the basis for the calculation of reference intakes for subjects with low energy intakes. 

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