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.

Effect of Nicotinamide Administration on the Tryptophan-Nicotinamide Pathway in Humans

2007 ◽  
Vol 77 (4) ◽  
pp. 255-262 ◽  
Author(s):  
Fukuwatari ◽  
Shibata
Keyword(s):  
Urinary Excretion ◽  
Young Women ◽  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
De Novo ◽  
Conversion Ratio ◽  
Xanthurenic Acid ◽  
Dependent Manner ◽  
Hydroxyanthranilic Acid ◽  
Dose Dependent

The vitamin nicotinamide is synthesized in the liver from tryptophan, and distributed to non-hepatic tissues. Although it is generally accepted that 60 mg tryptophan is equivalent to 1 mg nicotinamide in humans, the conversion ratio of tryptophan to nicotinamide is changeable. To determine if de novo nicotinamide synthesis from tryptophan is influenced by nicotinamide intake itself, six young women consumed controlled diets containing 30.4 or 24.8 mg niacin-equivalent nicotinamide supplements with 0, 89, 310, or 562 μmol/day (0, 10.9, 37.8, or 68.6 mg/day, respectively), and urinary excretion of intermediates and metabolites of the tryptophan-nicotinamide pathway were measured. Urinary excretion of nicotinamide metabolites increased linearly in a dose-dependent manner. None of the intermediates, including anthranilic acid, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, and quinolinic acid, changed at all, even when up to 562 μmol/day nicotinamide was given. That is, exogenous nicotinamide did not affect de novo nicotinamide synthesis. Therefore, when niacin equivalent is calculated, the intake of nicotinamide itself need not be considered as a factor that changes the tryptophan-nicotinamide conversion ratio.

scholarly journals Effects of Tranilast on the Urinary Excretion of Kynurenic and Quinolinic Acid under Conditions of L Tryptophan Loading

2013 ◽  
Vol 6 ◽  
pp. IJTR.S12797 ◽  
Author(s):  
Rowland R. Noakes
Keyword(s):  
Urinary Excretion ◽  
Quinolinic Acid ◽  
Kynurenic Acid ◽  
Competitive Inhibitor ◽  
Kynurenine Pathway ◽  
Tryptophan Metabolism ◽  
Autoimmune Response ◽  
Current Therapy ◽  
Indoleamine 2 ◽  
Hydroxyanthranilic Acid

The pathogenesis of morphea and other cutaneous sclerosing disorders remain poorly understood. Although they are considered to be autoimmune disorders, abnormal tryptophan metabolism may be involved. Current therapy is directed to supressing the autoimmune response. Demonstration of a therapeutic response to manipulation of the kynurenine pathway would both support a role for abnormal tryptophan metabolism and offer additional targets for therapy. Tranilast is a 3-hydroxyanthranilic acid derivative known to target the kynurenine pathway. The aim of this study was to see if tranilast lowered the urinary excretion of the kynurenine metabolites kynurenic and quinolinic acid under condition of L tryptophan loading in a volunteer. Mean baseline value for kynurenic acid and quinolinic acid were 1.1 and 2.1 mmol/mol creatinine, respectively. This rose to 5.6 and 3.8 mmol/mol creatinine respectively under conditions of L tryptophan loading 2 grams daily. Adding 1 g of tranilast daily lowered the values to 2.0 and 2.9 mmol/mol creatinine, respectively. These data suggest that tranilast acts as a competitive inhibitor of either indoleamine 2, 3-dioxygenase (IDO), tryptophan 2, 3 di-oxygenase (TDO) or both. As it involved only 1 subject, the results may not be representative of the larger population and must be considered preliminary.

scholarly journals Microbial tryptophan catabolism affects the vector competence of Anopheles

2021 ◽  
Author(s):  
Yuebiao Feng ◽  
Yeqing Peng ◽  
Han Wen ◽  
Xiumei Song ◽  
Yanpeng An ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Anopheles Stephensi ◽  
Vector Competence ◽  
Tryptophan Metabolism ◽  
Xanthurenic Acid ◽  
Peritrophic Matrix ◽  
Wild Type ◽  
Tryptophan Catabolism ◽  
Hydroxyanthranilic Acid ◽  
Wild Type Bacterium

AbstractThe influence of microbiota on mosquito physiology and vector competence is becoming increasingly clear but our understanding of interactions between microbiota and mosquitoes still remains incomplete. Here we show that gut microbiota of Anopheles stephensi, a competent malaria vector, participates mosquito tryptophan metabolism. Elimination of microbiota by antibiotics treatment leads to the accumulation of tryptophan (Trp) and its metabolites, kynurenine (Kyn), 3‐hydroxykynurenine (3‐HK) and xanthurenic acid (XA). Of these, 3‐HK impairs the structure of peritrophic matrix (PM), thereby promoting Plasmodium berghei infection. Among the major gut microbiota in An. stephensi, Pseudomonas alcaligenes plays a role in catabolizing 3‐HK as revealed by whole genome sequencing and LC‐MS metabolic analysis. The genome of P. alcaligenes encodes kynureninase (KynU) that is responsible for the conversion of 3‐HK to 3‐Hydroxyanthranilic acid (3‐HAA). Mutation of this gene abrogates the ability of P. alcaligenes to metabolize 3‐HK, which in turn abolishes its role on PM protection. Colonization of An. stephensi with KynU mutated P. alcaligenes fails to protect mosquitoes against parasite infection as effectively as those with wild type bacterium. In summary, we identify an unexpected function of gut microbiota in controlling mosquito tryptophan metabolism with the major consequences on vector competence.

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 An Investigation into the Temporal Reproducibility of Tryptophan Metabolite Networks Among Healthy Adolescents

2021 ◽  
Vol 14 ◽  
pp. 117864692110413
Author(s):  
Kolade Oluwagbemigun ◽  
Andrea Anesi ◽  
Gerard Clarke ◽  
Matthias Schmid ◽  
Fulvio Mattivi ◽  
...  
Keyword(s):  
Kynurenic Acid ◽  
Graphical Model ◽  
Bioactive Metabolites ◽  
Xanthurenic Acid ◽  
Dynamic Interactions ◽  
Healthy Adolescent ◽  
Time Points ◽  
Stable Pattern ◽  
Hydroxyanthranilic Acid ◽  
Network Approaches

Tryptophan and its bioactive metabolites are associated with health conditions such as systemic inflammation, cardiometabolic diseases, and neurodegenerative disorders. There are dynamic interactions among metabolites of tryptophan. The interactions between metabolites, particularly those that are strong and temporally reproducible could be of pathophysiological relevance. Using a targeted metabolomics approach, the concentration levels of tryptophan and 18 of its metabolites across multiple pathways was quantified in 24-hours urine samples at 2 time-points, age 17 years (baseline) and 18 years (follow-up) from 132 (52% female) apparently healthy adolescent participants of the DOrtmund Nutritional and Anthropometric Longitudinally Designed (DONALD) Study. In sex-specific analyses, we applied 2 network approaches, the Gaussian graphical model and Bayesian network to (1) explore the network structure for both time-points, (2) retrieve strongly related metabolites, and (3) determine whether the strongly related metabolites were temporally reproducible. Independent of selected covariates, the 2 network approaches revealed 5 associations that were strong and temporally reproducible. These were novel relationships, between kynurenic acid and indole-3-acetic acid in females and between kynurenic acid and xanthurenic acid in males, as well as known relationships between kynurenine and 3-hydroxykynurenine, and between 3-hydroxykynurenine and 3-hydroxyanthranilic acid in females and between tryptophan and kynurenine in males. Overall, this epidemiological study using network-based approaches shed new light into tryptophan metabolism, particularly the interaction of host and microbial metabolites. The 5 observed relationships suggested the existence of a temporally stable pattern of tryptophan and 6 metabolites in healthy adolescent, which could be further investigated in search of fingerprints of specific physiological states. The metabolites in these relationships may represent a multi-biomarker panel that could be informative for health outcomes.

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.

The Action of Pyridoxine in Primary Hyperoxaluria

1970 ◽  
Vol 38 (2) ◽  
pp. 277-286 ◽  
Author(s):  
Dorothy A. Gibbs ◽  
R. W. E. Watts
Keyword(s):  
Kynurenic Acid ◽  
Enzyme System ◽  
Primary Hyperoxaluria ◽  
Xanthurenic Acid ◽  
Normal Range ◽  
Before And After ◽  
Tryptophan Metabolite ◽  
Pre Treatment ◽  
Hydroxyanthranilic Acid ◽  
Urinary Oxalate Excretion

1. Evidence of deficiency of, antagonism to, or abnormal dependency upon pyridoxine has been sought in four patients with primary hyperoxaluria. The urinary excretion of kynurenine, 3-hydroxykyurenine, 3-hydroxyanthranilic acid, kynurenic acid and xanthurenic acid, before and after a loading dose of l-tryptophan was used to assess pyridoxine nutrition. 2. Three of the four patients studied had abnormal l-tryptophan metabolite excretion patterns, but these were not of the type which is associated with abnormalities of pyridoxine nutrition. 3. The changes which were observed are compatible with impaired conversion of kynurenine to 3-hydroxykynurenine by the NADH2 dependent kynurenine 3-hydroxylase (EC 1.99.1.5) enzyme system. 4. Large doses of pyridoxine hydrochloride reduced the urinary oxalate excretion by two of the patients to levels which were intermediate between the normal range and the pre-treatment values. This effect was maintained for 6 months, which was the longest period of observation. 5. It is concluded that this action of pyridoxine is mediated by a mechanism which does not involve the correction of an abnormality of pyridoxine metabolism.

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 Method for Evaluation of the Requirements of B-group Vitamins Using Tryptophan Metabolites in Human Urine

2015 ◽  
Vol 8 ◽  
pp. IJTR.S24412
Author(s):  
Katsumi Shibata ◽  
Junko Hirose ◽  
Tsutomu Fukuwatari
Keyword(s):  
Pantothenic Acid ◽  
Basal Diet ◽  
Tryptophan Metabolism ◽  
Xanthurenic Acid ◽  
Vitamin B ◽  
Japanese Adult ◽  
Beneficial Effects ◽  
Tryptophan Metabolites ◽  
Daily Urine ◽  
Hydroxyanthranilic Acid

Tryptophan metabolism is directly involved with B-group vitamins such as vitamin B2, niacin, and vitamin B6, and indirectly with vitamin B1 and pantothenic acid. We evaluated the validity of requirements of B-group vitamins set by the Dietary Reference Intakes for the Japanese (DRI-J). We investigated the fate of dietary tryptophan in 10 Japanese adult men who ate the same diet based on DRI-J during a 4-week study. Vitamin mixtures were administered based on the amounts in the basal diet during weeks 2, 3, and 4. Daily urine samples were collected eight times (days 1 and 5 in each week). Administration of vitamin mixtures had no effect on tryptophan metabolites such as anthranilic acid, kynurenic acid, xanthurenic acid, 3-hydroxyanthranilic acid, and quinolinic acid within individuals. Surplus administration of B-group vitamins against DRI-J requirements did not elicit beneficial effects on tryptophan metabolism. Our findings supported the requirements of B-group vitamins set by the DRI-J.

scholarly journals Establishment of an Early Diagnosis Model of Colon Cancerous Bowel Obstruction Based on 1HNMR

2021 ◽  
Author(s):  
Jie Zeng ◽  
Jin Peng ◽  
Hua Jiang ◽  
Pengchi Deng ◽  
Kexun Li ◽  
...  
Keyword(s):  
Early Diagnosis ◽  
Ferulic Acid ◽  
Bowel Obstruction ◽  
Tryptophan Metabolism ◽  
Control Group ◽  
Xanthurenic Acid ◽  
Gentisic Acid ◽  
The Future ◽  
Diagnosis Model ◽  
Hydroxyanthranilic Acid

Abstract Objective To prospectively establish an early diagnosis model of acute colon cancerous bowel obstruction by applying nuclear magnetic resonance hydrogen spectroscopy(1H-NMR) technology based metabolomics methods, combined with machine learning. Methods In this study, serum samples of 71 patients with acute bowel obstruction requiring emergency surgery who were admitted to the Emergency Department of Sichuan Provincial People's Hospital from December 2018 to November 2020 were collected within 2 hours after admission, and NMR spectroscopy data was taken after pretreatment. After postoperative pathological confirmation, they were divided into colon cancerous bowel obstruction (CBO) group and adhesive bowel obstruction (ABO) control group. Used MestReNova software to extract the two sets of spectra bins, and used the MetaboAnalyst5.0 website to perform partial least square discrimination (PLS-DA), combining the human metabolome database (HMDB) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) to find possible different Metabolites and related metabolic pathways. Results 22 patients were classified as CBO group and 30 were classified as ABO control group. Compared with ABO group, the level of Xanthurenic acid, 3-Hydroxyanthranilic acid, Gentisic acid, Salicyluric acid, Ferulic acid, Kynuric acid, CDP, Mandelic acid, NADPH, FAD, Phenylpyruvate, Allyl isothiocyanate, and Vanillylmandelic acid increased in the CBO group; while the lecel of L-Tryptophan and Bilirubin decreased (all P < 0.05). There were significant differences between two groups in the tryptophan metabolism, tyrosine metabolism, glutathione metabolism, phenylalanine metabolism and synthesis pathways of phenylalanine, tyrosine and tryptophan (all P < 0.05). Tryptophan metabolism pathway had the greatest impact (Impact = 0.19). The early diagnosis model of colon cancerous bowel was established based on the levels of six metabolites: Xanthurenic acid, 3-Hydroxyanthranilic acid, Gentisic acid, Salicylic acid, Ferulic acid and Kynuric acid (R2 = 0.995, Q2 = 0.931, RMSE = 0.239, AUC = 0.962). Conclusion This study firstly used serum to determine the difference in metabolome between patients with colon cancerous bowel obstruction and those with adhesive bowel obstruction. The study found that the metabolic information carried by the serum was sufficient to discriminate the two groups of patients and provided the theoretical supporting for the future using of the more convenient sample for the differential diagnosis of patients with colon cancerous bowel obstruction. Quantitative experiments on a large number of samples were still needed in the future.

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