Disease relevance of Xanthuric acid

• The Pseudomonas siderophore quinolobactin is synthesized from xanthurenic acid, an intermediate of the kynurenine pathway [1].
• Only 1 of the 11 subjects was found to have elevated homocysteine concentrations even though all subjects exhibited high urinary xanthurenic acid concentrations after a tryptophan load, a measure indicative of vitamin B-6 deficiency [2].
• KAT catalyses the transamination of kynurenine and 3-hydroxykynurenine to kynurenic acid and xanthurenic acid respectively, and the enzyme activity can be easily detected in E. coli cells [3].
• Vitamin B-6 status was evaluated according to several biological criteria (weight gain, urinary excretion of xanthurenic acid after tryptophan loading, plasma pyridoxal 5'-phosphate, apparent pyridoxal 5'-phosphate-saturation of liver kynureninase, urinary excretion of 4-pyridoxic acid and fecal output of vitamin B-6) [4].
• Xanthurenic acid is the metabolite which showed the most increased levels in urine during dermatitis [5].

Psychiatry related information on Xanthuric acid

• The xanthurenic acid (XA) flow in 24-hour urine following L-tryptophan loading was determined in a control group and in depressive patients divided into two DSM-III categories: minor depression (dysthymic disorder, atypical depression, adaptation disorder with depressive mood), and major depression [6].

High impact information on Xanthuric acid

• Differentiation of specialized transmission stages, the gametocytes, into male and female gametes is induced by a small mosquito molecule, xanthurenic acid (XA) [7].
• We also show that low concentrations of xanthurenic acid can act together with pH to induce gametogenesis in vitro [8].
• The gametocyte-activating factor xanthurenic acid stimulates an increase in membrane-associated guanylyl cyclase activity in the human malaria parasite Plasmodium falciparum [9].
• Xanthurenic acid (XA) has been quantified in the serum of normal and vitamin B6-deficient rabbits using high performance liquid chromatography [10].
• Oral glucose tolerance, urinary xanthurenic acid excretion, and plasma pyridoxal phosphate concentrations were determined in nine women taking oral contraceptives and in four controls [11].

Chemical compound and disease context of Xanthuric acid

• Thirteen women with chemical diabetes diagnosed in late pregnancy were found to excrete excessive amounts of urinary xanthurenic acid after a tryptophan load, indicative of a relative pyridoxine (vitamin B6) deficiency [12].
• Only two patients then had sufficiently impaired glucose tolerance to justify the diagnosis of gestational diabetes; Our results substantiated our hypothesis that increased xanthurenic-acid synthesis during pregnancy may cause gestational diabetes [13].
• The xanthurenic acid excretion in the 24-hour urine correlated significantly (p = 0.04) with urine volume, but did not correlated with age, sex, height, body-weight, urine pH and urinary output of creatinine or 17-hydroxysteroids [14].

Biological context of Xanthuric acid

• An end point of the xanthurenic acid accumulation in the cell is the cell death [15].
• In conclusion xanthurenic acid accumulation in cells abolished the regulatory function of the proteins 14-3-3 in the cell physiology and caused misfolding of the proteins leading to cell pathology [16].
• CONCLUSION: The deamination of 3-hydroxykynurenine resulted in the formation of a fluorescent substance which was identified as oxidized xanthurenic acid [17].
• Aconitase, the most sensitive enzyme to oxidative stress was inactivated effectively by xanthurenic acid and to a lesser extent by 8-quinolinol in the presence of ferrous sulfate [18].
• CONCLUSION: Xanthurenic acid interacts directly with Bcl-2 family proteins, inducing mitochondrial pathways of apoptosis and impairing mitochondrial functions [19].

Anatomical context of Xanthuric acid

• Cofilin dephosphorylation in the presence of xanthurenic acid was associated with lack of the apoptotic actin cytoskeleton disintegration [16].
• Xanthurenic acid provokes formation of unfolded proteins in endoplasmic reticulum of the lens epithelial cells [15].
• This study shows that accumulation of xanthurenic acid in the lens epithelial cells leads to an overexpression of endoplasmic reticulum (ER) resident stress chaperones proteins, glucose-regulated protein (Grp94), and calreticulin [15].
• Here we report that xanthurenic acid targets signalling proteins 14-3-3 into lysosomes leading to interruption protein/protein interaction [16].
• Here we report for the first time that with the increasing concentration of exogenous xanthurenic acid, there is a gradual increase in the number of oocysts in the mid-gut of infected mosquitoes [20].

Associations of Xanthuric acid with other chemical compounds

• With both Plasmodium falciparum and Plasmodium berghei, the tryptophan metabolite xanthurenic acid induces the release of motile male gametes from red blood cells (exflagellation), a prerequisite for fertilization [9].
• In contrast, a xanthurenic acid precursor (3-hydroxykynurenine), which is not an inducer of exflagellation, does not induce this guanylyl cyclase activity [9].
• Plasma PLP, urinary 4-pyridoxic acid (4-PA), net increase in plasma total homocysteine after a methionine load (DeltatHcy) and net increase in urinary xanthurenic acid after a tryptophan load (DeltaXA) were log-transformed to reach normality for statistical analyses [21].
• Iontophoretic application of a structural analogue of KYN which has no EAA receptor antagonist properties, xanthurenic acid, had no effect on glutamate, CSN or vagus nerve evoked discharge [22].
• Fl-X-aglycon and authentic xanthurenic acid (MW = 205) not only eluted at exactly the same retention time on HPLC but also revealed their protonated ions at the same m/z of 206.1 by positive ion analysis on HPLC-ESI-MS [23].

Gene context of Xanthuric acid

• Analysis of the supernatant by capillary electrophoresis and UV absorbance profile showed that the salivary glands contained xanthurenic acid, which was previously identified as GAF in the head of A. stephensi [24].
• Xanthurenic acid (XA) is a metabolite of this pathway and has recently been identified as a gamete activating factor (GAF) of the malarial parasite [25].
• A significantly higher excretion of xanthurenic acid in 24-hour urine, after an oral tryptophan load, was observed for Groups TAM and MA [26].
• Kynurenine formamidase inhibition by organophosphorous acid triesters and methylcarbamates is the proposed primary event resulting in increase in xanthurenic acid urinary excretion and plasma L-kynurenine [27].
• Urinary xanthurenic acid excretion (XA), plasma vitamin A and the folate content of the sera and red blood cells were significantly increased by OC treatment, although this excessive XA excretion was adequately corrected with 18 mg of daily vitamin B-6 supplementation [28].

Analytical, diagnostic and therapeutic context of Xanthuric acid

• Quantitation of xanthurenic acid in rabbit serum using high performance liquid chromatography [10].
• Bilateral microinjections of xanthurenic acid (100 mM, 50 nl) into the CVLM had no effect on the decrease in total lung resistance that was evoked by sciatic nerve stimulation [29].
• In this study we used HPLC and mass spectrometry to examine whether xanthurenic acid is indeed present in human lenses and, if so, the effect of age on its lenticular concentration [30].
• Gametocytemic blood was collected from 98 P. vivax-infected patients reporting to malaria clinics in Maesod and Maekasa Districts, Tak Province, Thailand. Briefly, gametogenesis was induced using xanthurenic acid and parasites were separated by density gradient centrifugation and then cultured in RPMI-1640, pH 7.8-8 [31].

References