Similarity Between the Action of Pteridines and Tryptophan Metabolites on Lipid Metabolism

Abstract Incorporation of fatty acids into phospholipids has been investigated using samples of rat liver tissue homogenate, Krebs-Ringer-phosphate buffer (pH=7.4) containing 0.3% albumin, fatty acid mixture and glycerol. The addition of anthranilic acid (2.2 and 4 nmol/g wet weight), kynurenic acid (4 and 40 nmol/ g wet weight), xanthurenic acid (4 and 40 nmol/g wet weight), picolinic acid (0.2 and 2 nmol/g wet weight) induced an increase of saturated and a decrease of polyunsaturated fatty acids incorporation into phospholipids as well as an eleyation of choksterol concentration in samples used for phospholipid biosynthesis in vitro. These changes were similar to those observed after addition of kynurenine and neopterin to the same test system, An inverse relationship has been observed after addition of nicotinic acid to samples used for phospholipid biosynthesis in vitro. Nicrotinic acid induced .1 decrease of saturated and an increase of unsaturated fatty acids incorporation into phospholipids as well as decrease of cholesterol concentration in samples, These changes were similar to those observed after addition of 3-hydroxykynurenine, 3-hydroxyanthranilic acid, quinolinic, acid, 5,6],8-tetrahydrobiopterin and its precursors to the same test system used rex phospholipid biosynthesis in vitro. In parallel anthranilic acid, kynurenic acid, xanthurenic acid and picolinic acid decrease while nicotinic acid increases membrane fluidity in the studied concentrations.

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Clinical relevance of depressed kynurenine pathway in episodic migraine patients: potential prognostic markers in the peripheral plasma during the interictal period

The Journal of Headache and Pain ◽

10.1186/s10194-021-01239-1 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Bernadett Tuka ◽

Aliz Nyári ◽

Edina Katalin Cseh ◽

Tamás Körtési ◽

Dániel Veréb ◽

...

Keyword(s):

Anthranilic Acid ◽

Clinical Relevance ◽

Kynurenic Acid ◽

Picolinic Acid ◽

Plasma Concentrations ◽

Episodic Migraine ◽

Kynurenine Pathway ◽

Xanthurenic Acid ◽

Control Subjects ◽

Healthy Control

Abstract Background Altered glutamatergic neurotransmission and neuropeptide levels play a central role in migraine pathomechanism. Previously, we confirmed that kynurenic acid, an endogenous glutamatergic antagonist, was able to decrease the expression of pituitary adenylate cyclase-activating polypeptide 1–38, a neuropeptide with known migraine-inducing properties. Hence, our aim was to reveal the role of the peripheral kynurenine pathway (KP) in episodic migraineurs. We focused on the complete tryptophan (Trp) catabolism, which comprises the serotonin and melatonin routes in addition to kynurenine metabolites. We investigated the relationship between metabolic alterations and clinical characteristics of migraine patients. Methods Female migraine patients aged between 25 and 50 years (n = 50) and healthy control subjects (n = 34) participated in this study. Blood samples were collected from the cubital veins of subjects (during both the interictal/ictal periods in migraineurs, n = 47/12, respectively). 12 metabolites of Trp pathway were determined by neurochemical measurements (UHPLC-MS/MS). Results Plasma concentrations of the most Trp metabolites were remarkably decreased in the interictal period of migraineurs compared to healthy control subjects, especially in the migraine without aura (MWoA) subgroup: Trp (p < 0.025), L-kynurenine (p < 0.001), kynurenic acid (p < 0.016), anthranilic acid (p < 0.007), picolinic acid (p < 0.03), 5-hydroxy-indoleaceticacid (p < 0.025) and melatonin (p < 0.023). Several metabolites showed a tendency to elevate during the ictal phase, but this was significant only in the cases of anthranilic acid, 5-hydroxy-indoleaceticacid and melatonin in MWoA patients. In the same subgroup, higher interictal kynurenic acid levels were identified in patients whose headache was severe and not related to their menstruation cycle. Negative linear correlation was detected between the interictal levels of xanthurenic acid/melatonin and attack frequency. Positive associations were found between the ictal 3-hydroxykynurenine levels and the beginning of attacks, just as between ictal picolinic acid levels and last attack before ictal sampling. Conclusions Our results suggest that there is a widespread metabolic imbalance in migraineurs, which manifests in a completely depressed peripheral Trp catabolism during the interictal period. It might act as trigger for the migraine attack, contributing to glutamate excess induced neurotoxicity and generalised hyperexcitability. This data can draw attention to the clinical relevance of KP in migraine.

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Effect of Sepiapterin, 7,8-Dihydrobiopterin, 5,6,7,8-Tetrahydrobiopterin and Xanthopterin on Cholesterol and Phospholipid Content and Phospholipid Biosynthesis in vitro

Pteridines ◽

10.1515/pteridines.1995.6.2.69 ◽

1995 ◽

Vol 6 (2) ◽

pp. 69-73

Author(s):

Vera Rudzite ◽

Edite Jurika ◽

Gabriele Baier-Bitterlich ◽

Helmut Wachter ◽

Dietmar Fuchs

Keyword(s):

Fatty Acids ◽

Incubation Medium ◽

Cholesterol Content ◽

Tissue Homogenate ◽

Phospholipid Content ◽

Acid Mixture ◽

Phospholipid Biosynthesis ◽

Wet Weight ◽

Fatty Acid Incorporation

Summary Incorporation of fatty acids into phospholipids has been investigated using samples of rat live tissue homogenate, Krebs-Ringer-phosphate buffer (pH = 7A) containing 0.3% albumin, farry acid mixture and glycerol. The addition of sepiapterin, 7,8-dihydrobiopterin and 5.6.7.8-tetrahydrobiopterin (5 and 30 pmol g wet weight) to incubation medium induced a decrease of saturated (stearic acid) and an increase of polyunsaturated (arachidonic acid) fatty acids incorporation into phospholipids. Cholesterol content decreased, but phospholiplid content did not change in samples containing sepiapterin, 7,8-dihydrobiopterin and 5,6,7,8-tetrahydrobiopterin. No changes of fatty acid incorporation into phospholipids as well as of the content of cholesterol and phospholipids were observed in samples after the addition of xanthopterin (4 and 20 nmol/g wet weight) to incubation medium for phospholipid biosynthesis in vitro. The observations made by incubation with 7,8-dihydrobiopterin, 5,6,7,8-tetrahydrobiopterin and sepiapterin where in opposite to those made earlier employing neopterin and using the same incubation procedure.

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Relationship between Serum Tryptophan and Tryptophan Metabolite Levels after Tryptophan Ingestion in Normal Subjects and Age-Related Cataract Patients

Clinical Science ◽

10.1042/cs0890591 ◽

1995 ◽

Vol 89 (6) ◽

pp. 591-599 ◽

Cited By ~ 17

Author(s):

Roger J. W. Truscott ◽

Anthony J. Elderfield

Keyword(s):

Anthranilic Acid ◽

Kynurenic Acid ◽

Normal Subjects ◽

Serum Levels ◽

Xanthurenic Acid ◽

Control Subjects ◽

Age Related ◽

Hydroxyanthranilic Acid ◽

And Control ◽

Cataract Patients

1. Cataract is the single major cause of blindness worldwide; however, the reasons for the development of this condition remain unknown. It has been suggested that the essential amino acid tryptophan may be implicated in the aetiology but definitive evidence has been lacking. 2. The serum levels of tryptophan and seven of its metabolites have been measured in both cataract patients and control subjects, after administration of tryptophan, in order to determine the typical response profile and to discover whether differences could be found in tryptophan metabolism in the two groups. 3. Tryptophan, kynurenine, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, 5-hydroxyanthranilic acid, 5-hydroxytryptophan and anthranilic acid were measured by HPLC with dual electrochemical and programmable wavelength fluorescence detection. Fasting cataract patients (n = 42) and control subjects (n = 37) were given an oral dose of l-tryptophan and sera were sampled at 0, 1, 2, 4 and 6 h. 4. Statistically significant differences in the distribution of data between the two groups were observed. The responses of kynurenine and 5-hydroxyanthranilic acid were higher in cataract patients, but those of kynurenic acid and total tryptophan were lower than in control subjects. No statistically significant differences in free tryptophan, anthranilic acid, 3-hydroxyanthranilic acid, xanthurenic acid or 5-hydroxytryptophan levels were noted. 5. We conclude that there is a major subgroup of age-related cataract patients with a dysfunction in the metabolism of tryptophan. This may be related to the onset of cataract. The mechanism remains to be established but may operate via the action of tryptophan metabolites, such as 5-hydroxyanthranilic acid, which become reactive towards protein upon oxidation.

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Influence of Kynurenine, Neopterin, Noradrenaline and Pyridoxal-5-Phosphate on Cholesterol and Phospholipid Content and Phospholipid Biosynthesis in vitro

Pteridines ◽

10.1515/pteridines.1993.4.3.126 ◽

1993 ◽

Vol 4 (3) ◽

pp. 126-130 ◽

Cited By ~ 3

Author(s):

Vera Rudzite ◽

Edite Jurika ◽

Gilbert Reibnegger ◽

Günter Weiss ◽

Helmut Wachter ◽

...

Keyword(s):

Fatty Acids ◽

Arachidonic Acid ◽

Fatty Acid ◽

Incubation Medium ◽

Tissue Homogenate ◽

Phospholipid Content ◽

Phospholipid Biosynthesis ◽

Acid Incorporation ◽

Wet Weight ◽

Fatty Acid Incorporation

Summary Incorporation of fatty acids into phospholipids has been investigated using samples of rat liver tissue homogenate, Krebs-Ringer-phosphate buffer (pH = 7.4) containing 0.3% albumin, fatty acid mixture and glyceroL The addition of L-kynurenine (4 nmol/g wet weight), D-eryhro-neopterin (5 and 30 pmol/g wet weight) and noradrenaline (4 nmol/g wet weight) to incubation medium induced an increase of saturated (palmitic acid) and decrease of poly-unsaturated (linoleic and arachidonic acid) fatty acids incorporation into phospholipids. The increase of saturated fatty acids incorporation into phospholipids was more pronounced after addition of neopterin and noradrenaline to the incubation medium while the decrease of linoleic and arachidonic acid synthesis was stimulated most with kynurenine. Moreover, kynurenine stimulated whereas neopterin depressed the oleic acid incorporation into phospholipids. These changes of fatty acid incorporation into phospholipids were followed by increase of cholesterol content in samples containing kynurenine, neopterin or noradrenalin. In contrast, phospholipid content decreased in samples containing kynurenine or noradrenalin, hut was not altered by supplementation of neopterin. Since the addition of kynurenine and neopterin to incubation medium for isolated fog heart resulted in an increased noradrenaline and decreased pyridoxal-5-phosphate content in the tissue, we also added pyridoxal-5-phosphate (4 nmol/g wet weight) to incubation medium for phospholipid biosynthesis. No change of the fatty acid incorporation into phospholipids as welI as the content of phospholipids and cholesterol in samples was observed.

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Quantitative Determination of Tryptophan Metabolites (via Kynurenine) in Biologic Fluids

Clinical Chemistry ◽

10.1093/clinchem/5.5.391 ◽

1959 ◽

Vol 5 (5) ◽

pp. 391-401 ◽

Cited By ~ 41

Author(s):

D Coppini ◽

C A Benassi ◽

M Montorsi

Keyword(s):

Quantitative Determination ◽

Rapid Method ◽

Methyl Ether ◽

Anthranilic Acid ◽

Kynurenic Acid ◽

Large Range ◽

Xanthurenic Acid ◽

Two Dimensional ◽

Tryptophan Metabolites

Abstract A simple and rapid method for the quantitative determination of eight tryptophan (via kynurenine) metabolites is described. The following compounds can be determined even when present in the same sample of urine, blood or spinal fluid: kynurenine, 3-hydroxykynurenine, Nα-acetylkynurenine, anthranilic and 3-hydroxyanthranilic acids, kynurenic and xanthurenic acids, 8-methyl ether of the xanthurenic acid. The compounds are separated by means of two-dimensional chromatography. Spots of kynurenic acid, Nα-acetylkynurenine and xanthurenic acid 8-methyl ether are eluted with ethanol and the absorbancies are read in the ultraviolet. An acetic solution of p-dimethylaminobenzaldehyde serves as eluent and chromogenic reagent for the spots of kynurenine and anthranilic acid. Spots corresponding to 3-hydroxykynurenine, xanthurenic and 3-hydroxyanthranilic acids are eluted with water and determined by means of the color developed with a diazo reagent. Kynurenic and xanthurenic acids can also be determined conveniently by means of a spectrophotofluorometric procedure. The reproducibility of the results is satisfactory over a large range, and very good for amounts of 1 to 5 µg.

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Difference and Similarity of Serotonin and Pteridines to Act on Lipid Metabolism

Pteridines ◽

10.1515/pteridines.1998.9.4.201 ◽

1998 ◽

Vol 9 (4) ◽

pp. 201-206

Author(s):

Vera Rudzite ◽

Edite Jurika ◽

Janis Jirgensons ◽

Bernhard Widner ◽

Guenter Weiss ◽

...

Keyword(s):

Arachidonic Acid ◽

Liver Homogenate ◽

Cholesterol Content ◽

Acid Mixture ◽

Phospholipid Biosynthesis ◽

Acid Incorporation ◽

Elevated Cholesterol ◽

Hydroxyindoleacetic Acid ◽

Wet Weight

Summary Incorporation of fatty acids into phospholipids has been investigated using samples of rat liver homogenate, Krebs-Ringer phosphate buffer (pH=7.4) containing 0.3% albumin, fatty acid mixture and glycerol. The addition of neopterin, serotonin (0.2 and 2.0 nmoljg wet weight) without iproniasid and 5- hydroxyindoleacetic acid (20.0 nmoljg wet weight) induced an increase of saturated and a decrease of unsaturated, especially arachidonic acid, incorporation into phospholipids. These changes were accompanied with elevated cholesterol content in samples. The addition of 5,6,7,8-tetrahydrobiopterin (5 and 30 pmolj g wet weight) and serotonin (0.2 and 2.0 nmoljg wet weight) together with iproniasid (10 nmoljg wet weight) to incubation medium for phospholipid biosynthesis in vitro induced a decrease of saturated and an increase of unsaturated, especially arachidonic acid, incorporation into phospholipids. These changes were accompanied with decreased cholesterol content in samples. The influence of serotonin without iproniasid and 5-hydroxyindoleacetic acid was similar to that of neopterin, kynurenine and noradrenaline observed earlier, while the influence of serotonin together with iproniasid was similar to that of 5,6,7,8- tetrahydrobiopterin and its precursors found earlier. Our results allow to suggest that in the studied concentrations serotonin increases, while 5-hydroxyindoleacetic acid decreases membrane fluidity.

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Effect of acetoacetate on urinary excretion of xanthurenic acid and other tryptophan metabolites in rats

British Journal Of Nutrition ◽

10.1079/bjn19690018 ◽

1969 ◽

Vol 23 (1) ◽

pp. 153-155 ◽

Cited By ~ 1

Author(s):

M. C. Nath ◽

N. V. Shastri

Keyword(s):

Body Weight ◽

Urinary Excretion ◽

Nicotinic Acid ◽

Kynurenic Acid ◽

Urine Samples ◽

Albino Rats ◽

Xanthurenic Acid ◽

Deficient Diet ◽

Tryptophan Metabolites

1. An experiment was performed to study the effect of sodium acetoacetate on urinary excretion of santhurenic acid and other tryptophan metabolites in male albino rats.2. Animals were fed on a nicotinic acid-deficient diet for a period of 3 weeks. The animals were then divided into two groups and, after the basal urinary excretion of the tryptophan metabolites had been estimated, the rats of both the groups were force-fed with L-tryptophan (100 mg per rat), the rats of the second group being simultaneously injected intraperitoncally with acetoacetate (200 mg/kg body-weight), and the urine samples during the following 24 h were collected and analysed.3. Acetoacetate-treated rats given tryptophan were found to excrete significantly greater amounts of kynurenine, hydroxykynurenine and xanthurenic acid than the corresponding control rats. There was no ditference between the amounts of kynurenic acid excreted by the animals in the two groups.

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Studies with tryptophan metabolites in vitro. Kynurenine metabolism in kidneys of mice infested with Schistosoma mansoni

Biochemical Journal ◽

10.1042/bj1090613 ◽

1968 ◽

Vol 109 (4) ◽

pp. 613-615 ◽

Cited By ~ 7

Author(s):

M. Samir Amer ◽

M. H. Abdel-Daim ◽

G. A. Abdel-Tawab

Keyword(s):

Schistosoma Mansoni ◽

Anthranilic Acid ◽

Kynurenic Acid ◽

Normal Mouse ◽

Pyridoxal Phosphate ◽

Tryptophan Metabolites ◽

Kynurenine Metabolism ◽

Bladder Tumours

The conversion in vitro of kynurenine into kynurenic acid and anthranilic acid in both normal kidneys and those obtained from mice infested with Schistosoma mansoni was investigated. Normal mouse kidneys seem to possess an excess of functional pyridoxal phosphate over those obtained from infested mice. Kynureninase and kynurenine transaminase in the latter kidneys are more easily inhibited by deoxypyridoxal phosphate and tartar emetic, indicating low stores of active pyridoxal phosphate. The possible implication of these findings in relation to the role of the kidneys in producing abnormal patterns of tryptophan metabolism and possibly contributing to the production of bladder tumours in bilharzial patients is discussed.

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