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

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.

scholarly journals Autobiographical Memory in Normal Ageing and Dementia

1991 ◽  
Vol 4 (4) ◽  
pp. 235-248 ◽  
Author(s):  
Harvey J. Sagar ◽  
Edith V. Sullivan ◽  
Suzanne Corkin
Keyword(s):  
Memory Function ◽  
Early Adulthood ◽  
Normal Subjects ◽  
Elderly Subjects ◽  
Retrieval Cues ◽  
Age Related ◽  
Normal Ageing ◽  
Severity Of Dementia ◽  
And Control ◽  
Cue Words

Autobiographical memories in young and elderly normal subjects are drawn mostly from the recent past but elderly subjects relate a second peak of memories from early adulthood. Memory for remote past public events is relatively preserved in dementia, possibly reflecting integrity of semantic relative to episodic memory. We examined recall of specific, consistent autobiographical episodes in Alzheimer's disease (AD) in response to cue words. Patients and control subjects drew most memories from the recent 20 years: episode age related to anterograde memory function but not subject age or dementia. Subjects also related a secondary peak of memories from early adulthood; episode age related to subject age and severity of dementia. The results suggest that preferential recall of memories from early adulthood is based on the salience of retrieval cues, altered by age and dementia, superimposed on a temporal gradient of semantic memory. Further, AD shows behavioural similarity to normal ageing.

Decreased α-Synuclein Serum Levels in Patients with Lewy Body Dementia Compared to Alzheimer’s Disease Patients and Control Subjects

2011 ◽  
Vol 31 (6) ◽  
pp. 413-416 ◽  
Author(s):  
Christoph Laske ◽  
Andreas J. Fallgatter ◽  
Elke Stransky ◽  
Katja Hagen ◽  
Daniela Berg ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Lewy Body ◽  
Lewy Body Dementia ◽  
Serum Levels ◽  
Control Subjects ◽  
And Control

Occlusal Force and Condylar Motion in Patients with Anterior Open Bite

2005 ◽  
Vol 84 (2) ◽  
pp. 133-137 ◽  
Author(s):  
S. Miyawaki ◽  
Y. Araki ◽  
Y. Tanimoto ◽  
A. Katayama ◽  
A. Fujii ◽  
...  
Keyword(s):  
Temporomandibular Disorders ◽  
Hypothesis Test ◽  
Test Group ◽  
Normal Subjects ◽  
Open Bite ◽  
Control Groups ◽  
Anterior Open Bite ◽  
Occlusal Force ◽  
Control Subjects ◽  
And Control

Patients with open bite often show a weak occlusal force and temporomandibular disorders (TMDs). If these are the main cause of open bite, it may be hypothesized that both pre-pubertal and adult open-bite patients would show a weak occlusal force and abnormal condylar motion. The purpose of this study was to test this hypothesis. Test group subjects consisted of 13 consecutive pre-pubertal and 13 adult patients with anterior open bite. They were compared with age-matched normal subjects. The adult open-bite group showed a weaker occlusal force and a shorter range of condylar motion compared with the control subjects. In the pre-pubertal subjects, however, there were no significant differences in the occlusal force and range of condylar motion between the open-bite and control groups. Therefore, these results suggest that a weak occlusal force or TMDs may not be the main cause of open bite.

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.

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

Pteridines ◽  
1999 ◽  
Vol 10 (3) ◽  
pp. 133-140 ◽  
Author(s):  
Vera Rudzite ◽  
Edite Jurika ◽  
Bernhard Widner ◽  
Dietmar Fuchs
Keyword(s):  
Fatty Acids ◽  
Nicotinic Acid ◽  
Anthranilic Acid ◽  
Kynurenic Acid ◽  
Picolinic Acid ◽  
Test System ◽  
Xanthurenic Acid ◽  
Phospholipid Biosynthesis ◽  
Wet Weight

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.

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.

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 Differential Effects of Three Verbal Punishers on the Disfluencies of Normal Speakers

1967 ◽  
Vol 10 (3) ◽  
pp. 496-505 ◽  
Author(s):  
Robert H. Brookshire ◽  
Richard R. Martin
Keyword(s):  
Normal Subjects ◽  
Read Aloud ◽  
Verbal Stimuli ◽  
Fourth Group ◽  
Differential Effects ◽  
The Third ◽  
Control Subjects ◽  
Random Schedule ◽  
And Control

One hundred normal subjects, divided into five groups, read aloud for 40 minutes. For the first 10 minutes (Baserate), subjects read without interruption. For the next 20 minutes (Conditioning), verbal stimuli contingent upon disfluency were delivered to three groups. One group received “wrong”; the second, “no”; and the third “huh-uh” for disfluency. A fourth group received “wrong” on a random schedule during Conditioning, while the fifth (control) received no verbal stimuli. During the last 10 minutes (Extinction), no verbal stimuli were delivered to any group. Random and Control subjects did not change disfluency rates, while subjects in all contingent conditions decreased disfluency in Conditioning. Contingent “wrong” produced the greatest decrement in disfluency, “no” the least, and “huh-uh” occupied a midpoint.

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.

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