A review of chromatographic methods for bioactive tryptophan metabolites, kynurenine, kynurenic acid, quinolinic acid, and others, in biological fluids.

2022 ◽  
Author(s):  
Takeshi Fukushima ◽  
Maho Umino ◽  
Tatsuya Sakamoto ◽  
Mayu Onozato
Keyword(s):  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Biological Fluids ◽  
Chromatographic Methods ◽  
Tryptophan Metabolites

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.

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. 

scholarly journals Association of Tryptophan Metabolites with Incident Type 2 Diabetes in the PREDIMED Trial: A Case–Cohort Study

2018 ◽  
Vol 64 (8) ◽  
pp. 1211-1220 ◽  
Author(s):  
Edward Yu ◽  
Christopher Papandreou ◽  
Miguel Ruiz-Canela ◽  
Marta Guasch-Ferre ◽  
Clary B Clish ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Hazard Ratio ◽  
Model Assessment ◽  
Incident Type ◽  
Incident Type 2 Diabetes ◽  
Tryptophan Metabolites ◽  
Incident Cases

Abstract BACKGROUND Metabolites of the tryptophan–kynurenine pathway (i.e., tryptophan, kynurenine, kynurenic acid, quinolinic acid, 3-hydroxyanthranilic) may be associated with diabetes development. Using a case–cohort design nested in the Prevención con Dieta Mediterránea (PREDIMED) study, we studied the associations of baseline and 1-year changes of these metabolites with incident type 2 diabetes (T2D). METHODS Plasma metabolite concentrations were quantified via LC-MS for n = 641 in a randomly selected subcohort and 251 incident cases diagnosed during 3.8 years of median follow-up. Weighted Cox models adjusted for age, sex, body mass index, and other T2D risk factors were used. RESULTS Baseline tryptophan was associated with higher risk of incident T2D (hazard ratio = 1.29; 95% CI, 1.04–1.61 per SD). Positive changes in quinolinic acid from baseline to 1 year were associated with a higher risk of T2D (hazard ratio = 1.39; 95% CI, 1.09–1.77 per SD). Baseline tryptophan and kynurenic acid were directly associated with changes in homeostatic model assessment for insulin resistance (HOMA-IR) from baseline to 1 year. Concurrent changes in kynurenine, quinolinic acid, 3-hydroxyanthranilic acid, and kynurenine/tryptophan ratio were associated with baseline-to-1-year changes in HOMA-IR. CONCLUSIONS Baseline tryptophan and 1-year increases in quinolinic acid were positively associated with incident T2D. Baseline and 1-year changes in tryptophan metabolites predicted changes in HOMA-IR. Tryptophan levels may initially increase and then deplete as diabetes progresses in severity.

Actions of kynurenic acid and quinolinic acid in the rat hippocampus in vivo

1985 ◽  
Vol 88 (3) ◽  
pp. 570-579 ◽  
Author(s):  
M.N. Perkins ◽  
T.W. Stone
Keyword(s):  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Rat Hippocampus

QUANTITATIVE CHROMATOGRAPHIC METHODS: PART 7. ISOLATION OF AMINO ACIDS FROM SERUM AND OTHER FLUIDS

1961 ◽  
Vol 39 (2) ◽  
pp. 439-451 ◽  
Author(s):  
C. K. Harris ◽  
E. Tigane ◽  
C. S. Hanes
Keyword(s):  
Amino Acids ◽  
Quantitative Analysis ◽  
Ion Exchange ◽  
Paper Chromatography ◽  
Biological Fluids ◽  
Inorganic Cations ◽  
Chromatographic Methods ◽  
Tissue Extracts

A method based on the use of miniature ion-exchange columns has been devised for isolating small amounts of amino acids from biological fluids and tissue extracts. The amino acids are isolated virtually free from proteins, sugars, and inorganic cations in a single treatment.Techniques are described for the preparation of solutions of the isolated amino acids for quantitative analysis by paper chromatography.

scholarly journals Effect of Tryptophan-Derived AhR Ligands, Kynurenine, Kynurenic Acid and FICZ, on Proliferation, Cell Cycle Regulation and Cell Death of Melanoma Cells—In Vitro Studies

2020 ◽  
Vol 21 (21) ◽  
pp. 7946
Author(s):  
Katarzyna Walczak ◽  
Ewa Langner ◽  
Anna Makuch-Kocka ◽  
Monika Szelest ◽  
Karolina Szalast ◽  
...  
Keyword(s):  
Cell Death ◽  
Protein Level ◽  
Kynurenic Acid ◽  
Melanoma Cells ◽  
Aryl Hydrocarbon ◽  
Tryptophan Metabolites ◽  
Rb Phosphorylation ◽  
Retinoblastoma Tumor ◽  
Barrier Tissues

Tryptophan metabolites: kynurenine (KYN), kynurenic acid (KYNA) and 6-formylindolo[3,2-b]carbazole (FICZ) are considered aryl hydrocarbon receptor (AhR) ligands. AhR is mainly expressed in barrier tissues, including skin, and is involved in various physiological and pathological processes in skin. We studied the effect of KYN, KYNA and FICZ on melanocyte and melanoma A375 and RPMI7951 cell toxicity, proliferation and cell death. KYN and FICZ inhibited DNA synthesis in both melanoma cell lines, but RPMI7951 cells were more resistant to pharmacological treatment. Tested compounds were toxic to melanoma cells but not to normal human adult melanocytes. Changes in the protein level of cyclin D1, CDK4 and retinoblastoma tumor suppressor protein (Rb) phosphorylation revealed different mechanisms of action of individual AhR ligands. Importantly, all tryptophan metabolites induced necrosis, but only KYNA and FICZ promoted apoptosis in melanoma A375 cells. This effect was not observed in RPMI7951 cells. KYN, KYNA and FICZ in higher concentrations inhibited the protein level of AhR but did not affect the gene expression. To conclude, despite belonging to the group of AhR ligands, KYN, KYNA and FICZ exerted different effects on proliferation, toxicity and induction of cell death in melanoma cells in vitro.

scholarly journals Nocturnal Gamma-Hydroxybutyrate Reduces Cortisol-Awakening Response and Morning Kynurenine Pathway Metabolites in Healthy Volunteers

2019 ◽  
Vol 22 (10) ◽  
pp. 631-639
Author(s):  
D A Dornbierer ◽  
M Boxler ◽  
C D Voegel ◽  
B Stucky ◽  
A E Steuer ◽  
...  
Keyword(s):  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Killer Cell ◽  
Affective State ◽  
Neuropsychiatric Disorders ◽  
Cortisol Awakening Response ◽  
Therapeutic Effects ◽  
Cell Counts ◽  
Acid Ratio ◽  
Gamma Hydroxybutyrate

Abstract Background Gamma-hydroxybutyrate (GHB; or sodium oxybate) is an endogenous GHB-/gamma-aminobutyric acid B receptor agonist. It is approved for application in narcolepsy and has been proposed for the potential treatment of Alzheimer’s disease, Parkinson’s disease, fibromyalgia, and depression, all of which involve neuro-immunological processes. Tryptophan catabolites (TRYCATs), the cortisol-awakening response (CAR), and brain-derived neurotrophic factor (BDNF) have been suggested as peripheral biomarkers of neuropsychiatric disorders. GHB has been shown to induce a delayed reduction of T helper and natural killer cell counts and alter basal cortisol levels, but GHB’s effects on TRYCATs, CAR, and BDNF are unknown. Methods Therefore, TRYCAT and BDNF serum levels, as well as CAR and the affective state (Positive and Negative Affect Schedule [PANAS]) were measured in the morning after a single nocturnal dose of GHB (50 mg/kg body weight) in 20 healthy male volunteers in a placebo-controlled, balanced, randomized, double-blind, cross-over design. Results In the morning after nocturnal GHB administration, the TRYCATs indolelactic acid, kynurenine, kynurenic acid, 3-hydroxykynurenine, and quinolinic acid; the 3-hydroxykynurenine to kynurenic acid ratio; and the CAR were significantly reduced (P < 0.05–0.001, Benjamini-Hochberg corrected). The quinolinic acid to kynurenic acid ratio was reduced by trend. Serotonin, tryptophan, and BDNF levels, as well as PANAS scores in the morning, remained unchanged after a nocturnal GHB challenge. Conclusions GHB has post-acute effects on peripheral biomarkers of neuropsychiatric disorders, which might be a model to explain some of its therapeutic effects in disorders involving neuro-immunological pathologies. This study was registered at ClinicalTrials.gov as NCT02342366.

Kynurenic acid-induced protection of neurochemical and behavioural deficits produced by quinolinic acid injections into the nucleus basalis of rats

1986 ◽  
Vol 68 (3) ◽  
pp. 317-321 ◽  
Author(s):  
Richard J. Beninger ◽  
Khem Jhamandas ◽  
Roland J. Boegman ◽  
Sherif R. El-Defrawy
Keyword(s):  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Nucleus Basalis ◽  
Behavioural Deficits

A review of chromatographic methods for the determination of water- and fat-soluble vitamins in biological fluids

2015 ◽  
Vol 39 (1) ◽  
pp. 132-148 ◽  
Author(s):  
Marta Karaźniewicz-Łada ◽  
Anna Główka
Keyword(s):  
Biological Fluids ◽  
Chromatographic Methods ◽  
Fat Soluble Vitamins
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