Xanthurenate

Kynurenine Pyrophosphate 3- and 5-Hydroxy -1- kynurenic and xanthurenic acid 119... 

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.

Dagley S, PA Johnson (1963) Microbial oxidation of kynurenic, xanthurenic and picolinic acids. Biochim Biophys Acta 78 577-587. 

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. 

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). 

Xanthommatin (58) is detected in blowflies of the genera Calliphora and Protophormia beside xanthurenic acid (52) and kynurenic acid (53) in the latter... 

A predominant toxin (51) from water beetles of the genus llybius (Table V) shows a UV absorption corresponding to hydroxyquinoline or hydroxyiso-quinoline. The H-NMR spectrum exhibits, beside signals of methyl ester and phenol, signals of five aromatic protons as both ABC and AB systems, the latter indicating two protons at C-3 and C-4 in quinoline. Since electron pyrolysis of 51 gives radioactive 8-hydroxyquinoline, its structure is identified as methyl 8-hydroxyquinoline-2-carboxylate (51) and confirmed by synthesis from xanthurenic acid (52) (Scheme 48) (101). The precursor of this alkaloid was shown to be tryptophan (444). 

Taurine conjugation with bile acids, phenylacetic acid, and indolylacetic acid seems to be a minor process in most species, but in the pigeon and ferret, it occurs extensively. Other infrequently reported conjugations include serine conjugation of xanthurenic acid in rats excretion of quinaldic acid as quinaldylglycyltaurine and quinaldylglycylglycine in the urine of the cat, but not of the rat or rabbit and conversion of furfural to furylacrylie acid in the dog and rabbit, but not in the rat, hen, or human. The dog and... 

Urine Hyperalbuminuria Healthy subjects 21 patients 29 1H NMR LC-MS/MS Lysine, glycine, alanine, valine, n-butyrate, 3-hydroxybutyrate, betaine, dimethylglycine, kynurenic acid, and xanthurenic acid (45)... 

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. 

Figure 8.4. Pathways of tryptophan metaholism. Tryptophan dioxygenase, EC 1.13.11.11 formylkynurenine formamidase, EC 3.5.1.9 kynurenine hydroxylase, EC 1.14.13.9 kynureninase, EC 3.7.1.3 3-hydroxyanthranilate oxidase, EC 1.10.3.5 picolinate carboxylase, EC 4.1.1.45 kynurenine oxoglutarate aminotransferase, EC 2.6.1.7 kynurenine glyoxylate aminotransferase, 2.6.1.63 tryptophan hydroxylase, EC 1.14.16.4 and 5-hydroxytryptophan decarboxylase, EC 4.1.1.26. Relative molecular masses (Mr) tryptophan, 204.2 serotonin, 176.2 kynurenine, 208.2 3-hydroxykynurenine, 223.2 kynurenic acid, 189.2 xanthurenic acid, 205.2 and quinolinic acid 167.1. CoA, coenzyme A.

A number of inborn errors of metabolism of the tryptophan oxidative pathway (see Figure 8.4) have been reported, aU of which result in the development of pellagra that responds to high doses of niacin. These conditions include vitamin Be-responsive xanthurenic aciduria, caused by a defect of kynureni-nase (Section 9.4.3) hydroxykynureninuria, apparentiy caused by a defect of kynureninase tryptophanuria, apparentiy caused by tryptophan dioxygenase deficiency a hereditary pellagra-like condition, apparentiy caused by an increase in activity of picoUnate carboxylase and Hartnup disease. 

As shown in Table 9.4, vitamin Be dependency has been reported in cases of type I primary hyperoxaluria, xanthurenic aciduria, homocystinuria, hypochromic sideroblastic anemia, gyrate atrophy with ornithinemia, and vitamin Be responsive infantile convulsions. In this last condition, the underlying defect has not been identified, but is almost certainly not impaired activity of glutamate decarboxylase. 

Urine xanthurenic acid after 2 g tryptophan load <65 xmol/24 h increase... 

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. 

Under normal conditions, the rate-limiting enzyme of the pathway is tryptophan dioxygenase (Section 8.3.2), and there is hide accumulation of intermediates. Kynurenine transaminase, the enzyme which catalyzes the transamination and ring closure of kynurenine to kynurenic acid, and of hydroxykynurenine to xanthurenic acid, has a high relative to the normal steady-state concentrations of its substrates in the liver. Kynureninase and kynurenine hydroxylase have lower values of K, so that there is normally litde accumuladon of kynurenine or hydroxykynurenine. 

Xanthurenic and kynurenic acids, and kynurenine and hydroxykynurenine, are easy to measure in urine, so the tryptophan load test, the ability to metabolize a test dose of 2 to 5 g (150 to 380 /xmol per kg of body weight) of tryptophan, was widely adopted as a convenient and sensitive index of vitamin Bg nutritional status. 

Induction of extrahepatic mdoleamine dioxygenase (which catalyzes the same reaction as tryptophan dioxygenase, albeit by a different mechanism) by bacterial lipopolysaccharides and mterferon-y may result in the production of relatively large amounts of kynurenine and hydroxykynurenine in tissues that lack the enzymes for onward metabolism. Kidney has kynurenine transaminase activity, and therefore extrahepatic metabolism of tryptophan may result in significant excretion of kynurenic and xanthurenic acids, even when vitamin Bg nutrition is adequate. 

As discussed in Section 8.3.3, estrogen metabolites inhibit kynureninase and reduce the activity of kynurenine hydroxylase to such an extent that, even without induction of tryptophan dioxygenase (Section 9.5.4.1), the activity of these enzymes is lower than is needed for the rate of flux through the pathway, thus leading to increased formation of xanthurenic and kynurenic acids. 

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