Tryptophan metabolites

Figure 30-16. Formation of xanthurenate in vitamin Bg deficienqr. Conversion of the tryptophan metabolite 3-hydroxykynurenine to 3-hydroxyanthranilate is impaired (see Figure 30-15). A large portion is therefore converted to xanthurenate.

Important tryptophan metabolites include serotonin, melanin, and melatonin. 

Griffiths, H.R, Lunec, J. and Blake, D.R. (1992). Oxygen radical-induced fluorescence in proteins identification of the fluorescent tryptophan metabolite N formyl kynurenine as a biological index of radical damage. Amino Acids 3, 183-194. 

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). 

Purines such as xanthine (91), hypoxanthine (92), guanine (93), and uric acid (95) are found in excreta of many insects (Table VI) 48). Uric acid (95) is known to be the main end product of nitrogen metabolism in almost all insects. Various purines are found in the wasp Vespa) and the sawfly Gilpinia) in common with other insects (Table VI). In addition, various pteridines occur in Vespa and in the honeybee (Table VI). The latter also contains xanthurenic acid (52) or kynurenic acid (53), xanthurenic acid 4,8-digiucoside (56), and a yellow pigment, xanthommatin (58), as tryptophan metabolites (Table V). 

The silkworm, Bombyx mori (Bombycidae), contains in various body parts simple alkylamines, tryptophan metabolites, and pteridines (Tables V, VI, and VIII). One of the pteridines, violapterin (78), is synthesized from isoxanthopterin (67) by isoxanthopterin deaminase, occurring in the larvae and adults, and is stored in situ in the larval and adult integument (80). In addition, sepiapterin deaminase in the integument of the lemon mutant silkworm catalyzes the deamination of sepiapterin (81) to 7,8-dihydro-6-lactyllumazine (79) (81). 

Some pteridines and uric acid (95) are detected in locusts of the genera Locust and Schistocerca (Table VI). Kynurine (54) is found in the genus Dociostaurus and xanthommatin (58) in the genus Locust, as tryptophan metabolites (Table V). 

Xanthommatin (58) and dihydroxanthommatin (59) are well-known representatives of the tryptophan metabolite, ommatine. Xanthommatin (58) shows a... 

The highly distorted octahedral complex [mer-V (pic) 3] (pic = picolinic acid, a tryptophan metabolite) oxidizes over time to the [VO(pic)2] complex in aqueous solution [39]. Conductivity measurements revealed that the species is a nonelectrolyte, and voltammetry indicated a reversible oxidation at 0.635 V and reduction at — 1.01 V versus Ag/AgCl, values which are more positive than usually observed for comparable complexes. This feature was attributed to delocalization of d electrons [39]. 

Catecholamines, nerve transmitters monitored in brain and heart patients, are separated on C18 using octane sulfonate ion pairing in 6% An/water (pH 3) with added EDTA and phosphate. Detection can be at UV, 270 nm, or by electrochemical detection at +0.72 V for maximum sensitivity. Other tyrosine and tryptophan metabolite neurotransmitters such as serotonin, VMA, and HMA can be analyzed with ion pairing and EC detection. 

Albro and Fishbein [93] compared 11 different silylating mixtures for the derivatiza-tion of tyrosine and tryptophan metabolites. BSTFA with the addition of TMCS is the most suitable reagent as far as quantitative reaction is concerned a mixture of BSTFA with TMSDEAand TMCS in pyridine (99 1 30 100, v/v) is recommended as a universal silylating agent. 

In P. semperviva it has been demonstrated that tryptophan is a precursor of psilocybin (93a). It was simultaneously suggested that a similar oxidation of tryptophan or a tryptophan metabolite at the 4-position constitutes an important intermediate stage in the biosynthesis of the ergot alkaloids from tryptophan. 

The tryptophan load test for vitamin Bg nutritional status (the ability to metabolize a test dose of tryptophan) is one of the oldest metabolic tests for functional vitamin nutritional status. It was developed as a result of observation of the excretion of an abnormal-colored compound, later identified as the tryptophan metabolite xanthurenic acid. 

Estimation of the vitamm Be requirements of infants presents a problem, and there is a clear need for further research. Human mUk, which must be assumed to be adequate for infant nutrition, provides only 2.5 to 3.5 //g of vitamin Be per g of protein-lower than the requirement for adults. Although their requirement for catabolism of amino acids may be lower than in adults (because they have net new protein synthesis), they must also increase their body content of the vitamin as they grow. Coburn (1994) noted that the requirement for growth in a number of animal species was less than that to maintain saturation of transaminases or rniriimum excretion of tryptophan metabolites after a test dose and was about 15 nmol per g of body weight gain across a range of species. 

As shown in Figure 8.2, NAD(P) can be synthesized from the tryptophan metabolite quinolinic acid. The oxidative pathway of tryptophan metabolism is shown in Figure 8.4. Under normed conditions, almost aU of the dietary intake of tryptophan, apart from the smedl 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 byway of 5-hydroxylation and decarboxylation to 5-hydroxytryptamine (serotonin), which is excreted mainly as 5-hydroxyindoleacetic acid. 

Studies on the Excretion of Tryptophan Metabolites after Test Load 88... 

It was furthermore reported (K20) that nicotinic acid-deficient animals would grow only if given tryptophan, thus suggesting the conversion of tryptophan to nicotinic acid. Not only is tryptophan converted to nicotinic acid but also kynurenine and 3-hydroxyanthranilic acid. The peculiar degradation of the latter to pyridine derivatives gave rise to many interesting investigations. 3-Hydroxyanthranilic acid is derived from 3-hydroxykynurenine, another important tryptophan metabolite, the his-... 

The first observation on the connection of human pathological conditions with abnormal excretion of tryptophan metabolites, through the kynurenine pathway, was made in 1931 (K13). 

In the same year paper chromatography was first attempted by Benassi (B4) for the simultaneous analysis of 8 tryptophan metabolites (kyn-urenine, 3-hydroxykynurenine, kynurenic acid, xanthurenic acid, anthra-nilic acid, 3-hydroxyanthranilic acid, 2-aminoacetophenone, and 2-amino-3-hydroxyacetophenone), separated by means of a mixtiue of methanol, n-butanol, benzene, and water and revealed through the fluorescence in ultraviolet light of 3655 A. Each compound elicits a different fluorescent color (cf. Table 1). 

Tompsett (T3) achieved a separate elution from cation or anion resin columns of several tryptophan metabolites which were then determined colorimetrically. Finally, Boyland and Williams (B18) quantitatively adsorbed on inactivated charcoal anthranilic acid, kynurenine, 3-hy-droxyanthranilic acid, 3-hydroxykynurenine, and the sulfuric acid ester derivatives of the two latter compounds from urine of normal controls and of patients with bladder cancer. After elution, the compounds were separated by gradient chromatography on Celite columns and determined colorimetrically or spectrophotometrically. 

Fic. 3. Chromatographic fractionation of a mixture of tryptophan metabolites on an ion-exchange column of Amberlite IR-120 ( 28 X 0.9 cm). The temperature was held at 37 °C and the flow rate was adjusted at 12 ml per hour with formic acid-pyridine buffers. The metabolite concentration is given as (ig/ml after fluorometric readings. Effluent was collected in 2-ml fractions. The following abbreviations are used KA, kynurenic acid XA, xanthurenic acid AHA, o-aminohippuric acid K, kynurenine 30HAA, 3-hydroxyanthranilic acid 30HK, 3-hydroxykynurenine. 

As previously mentioned, 3-hydroxyanthranilic acid was found chro-matographically by Musajo et al. (M18) in the urine of tuberculous patients. This was the starting point for an extensive investigation of tryptophan metabolites excreted spontaneously, i.e., by normal subjects or patients with different diseases all fed a normal diet without added tryptophan. 

According to all authors, normal subjects excrete only a few mg daily of the more important tryptophan metabolites. 

In conclusion, all human beings fed a free diet excrete daily only small quantities of tryptophan metabolites. However, in some diseases and in vitamin deficiency such a pattern can substantially change. 

The amounts of the two substances originally present in the urine were higher than those actually isolated. It must be emphasized, however, that tryptophan metabolites have rarely been extracted from urine when neither special diets nor supplementary tryptophan are used. Furthermore, urine of hemoblastotic patients can be considered, together with Calliphora erythrocephala pupae, as one of the rare natural sources of 3-hydroxykynurenine. 

Spontaneous Excretion of Tryptophan Metabolites in 28 Patients with Hodgkin s Disease... 

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