scholarly journals “Kynurenine switch” and obesity

2022 ◽  
Vol 20 (4) ◽  
pp. 103-111
Author(s):  
A. V. Shestopalov ◽  
O. P. Shatova ◽  
M. S. Karbyshev ◽  
A. M. Gaponov ◽  
N. E. Moskaleva ◽  
...  
Keyword(s):  
Blood Serum ◽  
Healthy Volunteers ◽  
Quinolinic Acid ◽  
High Performance ◽  
Kynurenic Acid ◽  
Serum Levels ◽  
Xanthurenic Acid ◽  
Obese Patients ◽  
Tryptophan Metabolites ◽  
Eukaryotic Origin

Aim. To assess the concentrations of bacterial and eukaryotic metabolites mainly involved in indole, kynurenine, and serotonin pathways of tryptophan metabolism in a cohort of patients with obesity. Materials and methods. Using high-performance liquid chromatography with mass spectrometric detection, the concentrations of several serum metabolites, such as kynurenine, kynurenic acid, anthranilic acid, xanthurenic acid, quinolinic acid, 5-hydroxyindole-3-acetate, tryptamine, serotonin, indole-3-lactate, indole-3-acetate, indole-3- butyrate, indole-3-carboxaldehyde, indole-3-acrylate, and indole-3-propionate, were analyzed in a cohort of obese patients compared with healthy volunteers.Results. It was found that serum levels of tryptophan metabolites of microbial and eukaryotic origin were significantly increased in obese patients. Therefore, the concentration of kynurenine in the blood serum in obese patients was 2,413 ± 855 nmol / l, while in healthy volunteers of the same age group, the level of kynurenine in the blood serum was 2,122 ± 863 nmol / l. In obese patients, two acids formed due to kynurenine metabolism; the concentrations of kynurenic and quinolinic acids were increased in the blood serum. The concentration of kynurenic acid in the blood serum in obese patients was 21.1 ± 9.26 nmol / l, and in healthy patients, it was 16.8 ± 8.37 nmol / l. At the same time, the level of quinolinic acid in the blood serum in obese patients was 73.1 ± 54.4 nmol / l and in healthy volunteers – 56.8 ± 34.1 nmol / l. Normally, the level of quinolinic acid is 3.4 times higher than the concentration of kynurenic acid, and in case of obesity, there is a comparable increase in these acids in the blood serum.From indole derivatives, mainly of microbial origin, the concentrations of indole-3-lactate, indole-3-butyrate, and indole-3-acetate were significantly increased in the blood serum of obese patients. In obese patients, the serum concentration of 5-hydroxyindole-3-acetate was elevated to 74.6 ± 75.8 nmol / l (in healthy volunteers – 59.4 ± 36.6 nmol / l); indole-3-lactate – to 523 ± 251 nmol / l (in healthy volunteers – 433 ± 208 nmol / l); indole-3-acetate – to 1,633 ± 1,166 nmol / l (in healthy volunteers – 1,186 ± 826 nmol / l); and indole-3-butyrate – to 4.61 ± 3.31 nmol / l (in healthy volunteers – 3.85 ± 2.51 nmol / l).Conclusion. In case of obesity, the utilization of tryptophan was intensified by both the microbiota population and the macroorganism. It was found that obese patients had higher concentrations of kynurenine, quinolinic and kynurenic acids, indole-3-acetate, indole-3-lactate, indole-3-butyrate, and 5-hydroxyindole-3-acetate. Apparently, against the background of increased production of proinflammatory cytokines by adipocytes in obese patients, the “kynurenine switch” was activated which contributed to subsequent overproduction of tryptophan metabolites involved in the immune function of the macroorganism. 

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

1995 ◽  
Vol 89 (6) ◽  
pp. 591-599 ◽  
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.

scholarly journals Organ Correlation with Tryptophan Metabolism Obtained by Analyses of TDO-KO and QPRT-KO Mice

2016 ◽  
Vol 9 ◽  
pp. IJTR.S37984 ◽  
Author(s):  
Katsumi Shibata ◽  
Tsutomu Fukuwatari
Keyword(s):  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Conversion Ratio ◽  
Tryptophan Metabolism ◽  
Limiting Factors ◽  
Xanthurenic Acid ◽  
Wild Type ◽  
Organ Specific ◽  
Hydroxyanthranilic Acid ◽  
Rate Limiting

The aim of this article is to report the organ-specific correlation with tryptophan (Trp) metabolism obtained by analyses of tryptophan 2,3-dioxygenase knockout (TDO-KO) and quinolinic acid phosphoribosyltransferase knockout (QPRT-KO) mice models. We found that TDO-KO mice could biosynthesize the necessary amount of nicotinamide (Nam) from Trp, resulting in the production of key intermediate, 3-hydroxyanthranilic acid. Upstream metabolites, such as kynurenic acid and xanthurenic acid, in the urine were originated from nonhepatic tissues, and not from the liver. In QPRT-KO mice, the Trp to quinolinic acid conversion ratio was 6%; this value was higher than expected. Furthermore, we found that QPRT activity in hetero mice was half of that in wild-type (WT) mice. Urine quinolinic acid levels remain unchanged in both hetero and WT mice, and the conversion ratio of Trp to Nam was also unaffected. Collectively, these findings show that QPRT was not the rate-limiting enzyme in the conversion. In conclusion, the limiting factors in the conversion of Trp to Nam are the substrate amounts of 3-hydroxyanthranilic acid and activity of 3-hydroxyanthranilic acid 3,4-dioxygenase in the liver.

scholarly journals Circulating Antibodies to IDO/THO Pathway Metabolites in Alzheimer's Disease

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
S. Duleu ◽  
A. Mangas ◽  
F. Sevin ◽  
B. Veyret ◽  
A. Bessede ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Chronic Diseases ◽  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Tryptophan Hydroxylase ◽  
Elisa Method ◽  
Tryptophan Metabolites ◽  
Circulating Antibodies ◽  
Tryptophan Derivatives

In Alzheimer's disease, indoleamine 2,3-dioxygenase and tryptophan hydroxylase are known to induce an overproduction of neurotoxic compounds, such as quinolinic acid and 3-hydroxykynurenine from the former, and 5-hydroxytryptophol and 5-methoxytryptophol from the latter. Other compounds, such as kynurenic acid, serotonin, and melatonin are produced via the same pathways. An improved ELISA method identified circulating antibodies directed against these compounds, linked to proteins, as previously described for other chronic diseases. This describes how only the A isotype of circulating immunoglobulins recognized a pattern of conjugated tryptophan metabolites in the sera of Alzheimer patients. These data indirectly confirmed the involvement of tryptophan derivatives in the pathogenic processes of Alzheimer's disease. Further studies are required to evaluate the relevance of these antibody patterns in monitoring this disease.

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

1959 ◽  
Vol 5 (5) ◽  
pp. 391-401 ◽  
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.

THE INFLUENCE OF ACUPUNCTURE ON BLOOD SERUM LEVELS OF TRYPTOPHAN IN HEALTHY VOLUNTEERS SUBJECTED TO KETAMINE ANESTHESIA

1982 ◽  
Vol 7 (2) ◽  
pp. 123-132 ◽  
Author(s):  
C. Costa ◽  
F. Ceccherelli ◽  
F. Ambrosio ◽  
P. Baron ◽  
A. De Antoni ◽  
...  
Keyword(s):  
Blood Serum ◽  
Healthy Volunteers ◽  
Serum Levels ◽  
Ketamine Anesthesia

URINARY EXCRETION OF TRYPTOPHAN METABOLITES IN THE HEALTHY INFANT

PEDIATRICS ◽  
1962 ◽  
Vol 30 (4) ◽  
pp. 585-591
Author(s):  
Franco Vassella ◽  
Bo Hellström ◽  
Bo Wengle
Keyword(s):  
Body Weight ◽  
Urinary Excretion ◽  
Paper Chromatography ◽  
Kynurenic Acid ◽  
Healthy Infant ◽  
Xanthurenic Acid ◽  
Two Dimensional ◽  
Healthy Infants ◽  
Tryptophan Metabolites ◽  
Hydroxyanthranilic Acid

Urinary excretion of tryptophan metabolites was studied qualitatively by two-dimensional paper chromatography in a group of 50 healthy infants with no tryptophan supplementation. Twenty-two infants of this group were given 100 mg of L-tryptophan per kilogram of body-weight, and the 24-hour urinary excretions of kynurenine, kynurenic acid, 3-hydroxykynurenine, 3-hydroxyanthranilic acid, and xanthurenic acid were estimated by quantitative paper chromatography. A high excretion of kynurenine was found to be a distinguishing feature. Various possibilities to explain this difference as compared to adults are discussed.

Decreased levels of kynurenic acid in prefrontal cortex in a genetic animal model of depression

2016 ◽  
Vol 29 (1) ◽  
pp. 54-58 ◽  
Author(s):  
Xi-Cong Liu ◽  
Sophie Erhardt ◽  
Michel Goiny ◽  
Göran Engberg ◽  
Aleksander A. Mathé
Keyword(s):  
Prefrontal Cortex ◽  
Rat Model ◽  
High Performance ◽  
Kynurenic Acid ◽  
Kynurenine Pathway ◽  
Genetic Animal Model ◽  
Animal Model Of Depression ◽  
Tryptophan Metabolites ◽  
Sensitive Line

ObjectiveThere is a growing interest in the role of kynurenine pathway and tryptophan metabolites in the pathophysiology of depression. In the present study, the metabolism of tryptophan along the kynurenine pathway was analysed in a rat model of depression.MethodsKynurenic acid (KYNA) and 3-hydroxykynurenine (3-HK) were measured by high-performance liquid chromatography (HPLC) in prefrontal cortex (PFC) and frontal cortex (FC) in a rat model of depression, the Flinders Sensitive Line (FSL) and their controls, the Flinders Resistant Line (FRL) rats. In addition, KYNA was also measured in hippocampus, striatum and cerebellum.ResultsKYNA levels were reduced in the PFC of FSL rats compared with FRL rats, but did not differ with regard to the FC, hippocampus, striatum or cerebellum. 3-HK levels in PFC and FC, representing the activity of the microglial branch of the kynurenine pathway, did not differ between the FSL and FRL strains.ConclusionOur results suggest an imbalanced metabolism of the kynurenine pathway in the PFC of FSL rats.

Eosinophil Cationic Protein in Nasal Secretions and Blood Serum in Grass-Pollen Allergic Rhinitis

1996 ◽  
Vol 10 (5) ◽  
pp. 319-322 ◽  
Author(s):  
L. Klimek ◽  
H. Riechelmann ◽  
R. Amedee
Keyword(s):  
Allergic Rhinitis ◽  
Blood Serum ◽  
Healthy Volunteers ◽  
Grass Pollen ◽  
Eosinophil Cationic Protein ◽  
Serum Levels ◽  
Eosinophilic Inflammation ◽  
Cationic Protein ◽  
Nasal Secretions ◽  
Pollen Exposure

Concentration of the Eosinophil Cationic Protein (ECP) measured in different body fluids has been demonstrated to be a good marker of eosinophilic inflammation. In allergic asthma, ECP levels in both broncho-alveolar-lavage (BAL) fluid and serum can be used to monitor disease activity. In allergic rhinitis, the value of ECP determinations in serum and nasal secretions was not directly compared, so far. In the present study, ECP levels in blood serum (Se) and nasal secretions (NS) of grass pollen allergic and healthy individuals under pollen exposure were analyzed. Forty-three grass-pollen allergic subjects and 19 healthy volunteers were included. Grass-pollen counts were measured using Burkhard traps and a symptom scoring performed. In the allergic subjects, the mean ECP concentration in nasal secretions was 789 ± 515 ng/mL compared with 12.1 ± 7.4 ng/mL in serum; in the healthy volunteers it was 29.6 ± 15.4 ng/mL in NS compared to 9.4 ± 6.9 ng/mL in Se. ECP concentration in NS was significantly higher in allergic than in healthy subjects (P < 0.001) and in both significantly higher than in Se (P < 0.01). ECP concentration in Se did not differ significantly in patients and healthy volunteers (P > 0.05). In the allergic subjects, ECP concentration in NS but not in Se was closely correlated to symptom score and pollen exposure. We conclude that ECP levels in NS are a better marker of eosinophilic inflammation in allergic rhinitis than ECP serum levels.

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

1969 ◽  
Vol 23 (1) ◽  
pp. 153-155 ◽  
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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