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 Tryptophan metabolism in vitamin B6-deficient mice

1990 ◽  
Vol 63 (1) ◽  
pp. 27-36 ◽  
Author(s):  
David A. Bender ◽  
Eliud N. M. Njagi ◽  
Paul S. Danielian
Keyword(s):  
Urinary Excretion ◽  
Intraperitoneal Injection ◽  
Vitamin B6 ◽  
Isolated Hepatocytes ◽  
Tryptophan Metabolism ◽  
Xanthurenic Acid ◽  
Vitamin B ◽  
Tryptophan Metabolites ◽  
Deficient Mice

Vitamin B6 deficiency was induced in mice by maintenance for 4 weeks on a vitamin B6-free diet. Tryptophan metabolism was assessed by determining the urinary excretion of tryptophan metabolites, the metabolism of [14C]tryptophan in vivo and the formation of tryptophan and niacin metabolites by isolated hepatocytes. The vitamin B6-deficient animals excreted more xanthurenic acid and 3-hydroxykynurenine, and less of the niacin metabolites N1-methyl nicotinamide and methyl-2-pyridone-4-carboxamide, than did control animals maintained on the same diet supplemented with 5 mg vitamin B6/kg. After intraperitoneal injection of [14C]tryptophan, vitamin B6-deficient mice showed lower liberation of14CO2 from [methylene-14C]tryptophan and [U-14C]tryptophan than did controls, indicating impairment of kynureninase (EC 3.7.1.3) activity. There was no difference between the two groups of animals in the metabolism of [ring-2-14C]tryptophan. Hepatocytes isolated from the vitamin B6-deficient animals formed more 3-hydroxykynurenine and xanthurenic acid than did cells from control animals, but also formed more NADP and free niacin.

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.

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.

scholarly journals The vitamin B6 status of pigs given a diet containing linseed meal

1977 ◽  
Vol 37 (3) ◽  
pp. 321-331 ◽  
Author(s):  
H. N. Bishara ◽  
H. F. Walker
Keyword(s):  
Cell Volume ◽  
Packed Cell Volume ◽  
Vitamin B6 ◽  
Nitrogen Retention ◽  
Basal Diet ◽  
Xanthurenic Acid ◽  
Vitamin B ◽  
Linseed Meal ◽  
Load Tests

1. Pigs consuming a diet containing 300 g linseed meal/kg and a pyridoxine supplement showed greater growth, nitrogen retention, blood packed cell volume and haemoglobin than those receiving only the basal diet.2. Tryptophan-load tests on unsupplemented pigs revealed an increased excretion of kynurenine, Nα-acetylkynurenine and xanthurenic acid compared to those receiving additional pyridoxine.3. The results suggest that the unsupplemented pigs were marginally deficient in vitamin B6.4. When the same diet was fed to rats there was no evidence of vitamin B6 deficiency.

scholarly journals Tryptophan catabolites as metabolic markers of vitamin B-6 status evaluated in cohorts of healthy adults and cardiovascular patients

2019 ◽  
Vol 111 (1) ◽  
pp. 178-186 ◽  
Author(s):  
Arve Ulvik ◽  
Øivind Midttun ◽  
Adrian McCann ◽  
Klaus Meyer ◽  
Grethe Tell ◽  
...  
Keyword(s):  
Health Study ◽  
Xanthurenic Acid ◽  
Vitamin B ◽  
Cross Sectional ◽  
Metabolic Markers ◽  
Simple Index ◽  
Low Concentrations ◽  
Cardiovascular Patients ◽  
Standardized Regression Coefficients ◽  
Hydroxyanthranilic Acid

ABSTRACT Background Vitamin B-6 status is routinely measured as pyridoxal 5′-phosphate (PLP) in plasma. Low concentrations of PLP are associated with rheumatic, cardiovascular, and neoplastic diseases. We have previously shown that vitamin B-6 status affects the kynurenine (Kyn) pathway of tryptophan (Trp) catabolism. Objective This study aimed to comprehensively evaluate the use of Kyns as potential markers of functional vitamin B-6 status across 2 large cohorts. Methods We measured circulating concentrations of the first 6 metabolites in the Trp catabolic pathway by LC–MS-MS in the community-based Hordaland Health Study (HUSK; n = 7017) and cardiovascular patient–based Western Norway Coronary Angiography Cohort (WECAC; n = 4161). Cross-sectional and longitudinal associations of plasma PLP with Kyns were estimated using linear and nonlinear regression–based methods. Results 3′-Hydroxykynurenine (HK), a substrate, and all 4 products formed directly by the PLP-dependent enzymes kynurenine transaminase and kynureninase contributed to the explanation of circulating PLP in multivariable-adjusted regression models. The construct HK:(kynurenic acid + xanthurenic acid + 3′-hydroxyanthranilic acid + anthranilic acid), termed HK ratio (HKr), was related to plasma PLP with standardized regression coefficients (95% CIs) of −0.47 (−0.49, −0.45) and −0.46 (−0.49, −0.43) in HUSK and WECAC, respectively. Across strata of cohort and sex, HKr was 1.3- to 2.7-fold more sensitive, but also 1.7- to 2.9-fold more specific to changes in PLP than a previously proposed marker, HK:xanthurenic acid. Notably, the association was strongest at PLP concentrations < ∼20 nmol/L, a recognized threshold for vitamin B-6 deficiency. Finally, PLP and HKr demonstrated highly sex-specific and corroborating associations with age. Conclusions The results demonstrate that by combining 5 metabolites in the Kyn pathway into a simple index, HKr, a sensitive and specific indicator of intracellular vitamin B-6 status is obtained. The data also underscore the merit of evaluating alterations in Kyn metabolism when investigating vitamin B-6 and health.

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.

scholarly journals Chronic Unpredictable Stress Alters Brain Tryptophan Metabolism and Impairs Working Memory in Mice without Causing Depression-Like Behaviour

2021 ◽  
pp. 1-10
Author(s):  
Jason C. O’Connor ◽  
Grace A. Porter ◽  
Jason C. O’Connor
Keyword(s):  
Working Memory ◽  
Picolinic Acid ◽  
Kynurenine Pathway ◽  
Tryptophan Metabolism ◽  
Xanthurenic Acid ◽  
Chronic Unpredictable Stress ◽  
Nesting Behaviour ◽  
Tryptophan Metabolites ◽  
Hydroxyindoleacetic Acid ◽  
The Brain

Chronic stress is a well-known risk factor in major depressive disorder and disrupts the kynurenine and serotonin pathways of tryptophan metabolism. Here, we characterize the temporal central and peripheral changes in tryptophan metabolism and concomitant depressive-like behavioural phenotype induced during the progression of chronic unpredictable stress (CUS). Mice were exposed to 0, 10, 20, or 30 days of CUS followed by a panel of behavioural assays to determine depressive-like phenotypes. Immediately after behavioural testing, plasma and brain tissue were collected for metabolic analysis. While anhedonia-like and anxiety-like behaviours were unaffected by stress, nesting behaviour and cognitive deficits became apparent in response to CUS exposure. While CUS caused a transient reduction in circulating quinolinic acid, no other tryptophan metabolites significantly changed in response to CUS. In the brain, tryptophan, kynurenine, picolinic acid, and 5-hydroxyindoleacetic acid concentrations were significantly elevated in CUS-exposed mice compared with non-stress control animals, while kynurenic acid, xanthurenic acid, and serotonin decreased in CUS-exposed mice. Metabolic turnover of serotonin to the major metabolite 5-hydroxyindoleacetic acid was markedly increased in response to CUS. These results suggest that CUS impairs hippocampal-dependent working memory and enhances nascent nesting behaviour in C57BL/6J male mice, and these behaviours are associated with increased brain kynurenine pathway metabolism leading to accumulation of picolinic acid and a significant reduction in serotonin levels.

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.

scholarly journals Effects of Various Kynurenine Metabolites on Respiratory Parameters of Rat Brain, Liver and Heart Mitochondria

2016 ◽  
Vol 9 ◽  
pp. IJTR.S37973 ◽  
Author(s):  
Halina Baran* ◽  
Katrin Staniek ◽  
Melanie Bertignol-Spörr ◽  
Martin Attam ◽  
Carina Kronsteiner ◽  
...  
Keyword(s):  
Complex I ◽  
Clinical Symptoms ◽  
Liver Mitochondria ◽  
Brain Mitochondria ◽  
Heart Mitochondria ◽  
Xanthurenic Acid ◽  
Respiratory Parameters ◽  
Tryptophan Metabolites ◽  
Hydroxyanthranilic Acid ◽  
Oxygen Ratio

Previously, we demonstrated that the endogenous glutamate receptor antagonist kynurenic acid dose-dependently and significantly affected rat heart mitochondria. Now we have investigated the effects of L-tryptophan, L-kynurenine, 3-hydroxykynurenine and kynurenic, anthranilic, 3-hydroxyanthranilic, xanthurenic and quinolinic acids on respiratory parameters (ie, state 2, state 3), respiratory control index (RC) and ADP/oxygen ratio in brain, liver and heart mitochondria of adult rats. Mitochondria were incubated with glutamate/malate (5 mM) or succinate (10 mM) and in the presence of L-tryptophan metabolites (1 mM) or in the absence, as control. Kynurenic and anthranilic acids significantly reduced RC values of heart mitochondria in the presence of glutamate/malate. Xanthurenic acid significantly reduced RC values of brain mitochondria in the presence of glutamate/malate. Furthermore, 3-hydroxykynurenine and 3-hydroxyanthranilic acid decreased RC values of brain, liver and heart mitochondria using glutamate/malate. In the presence of succinate, 3-hydroxykynurenine and 3-hydroxyanthranilic acid affected RC values of brain mitochondria, whereas in liver and heart mitochondria only 3-hydroxykynurenine lowered RC values significantly. Furthermore, lowered ADP/oxygen ratios were observed in brain mitochondria in the presence of succinate with 3-hydroxykynurenine and 3-hydroxyanthranilic acid, and to a lesser extent with glutamate/malate. In addition, 3-hydroxyanthranilic acid significantly lowered the ADP/oxygen ratio in heart mitochondria exposed to glutamate/malate, while in the liver mitochondria only a mild reduction was found. Tests of the influence of L-tryptophan and its metabolites on complex I in liver mitochondria showed that only 3-hydroxykynurenine, 3-hydroxyanthranilic acid and L-kynurenine led to a significant acceleration of NADH-driven complex I activities. The data indicate that L-tryptophan metabolites had different effects on brain, liver and heart mitochondria. Alterations of L-tryptophan metabolism might have an impact on the bioenergetic activities of brain, liver and/or heart mitochondria and might be involved in the development of clinical symptoms such as cardiomyopathy, hepatopathy and dementia.

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