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Results for “Tryptophan Metabolism Alterations”

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At least 19 recordsLinked to original sources
PubMed2003

Experimental evaluation of an altered tryptophan metabolism in fibromyalgia.

Fibromyalgia (FM) is a prevalent syndrome with chronic pain and a hypothesised underlying disturbance of the tryptophan (TRP) metabolism. We performed a tryptophan depletion (TD) test in 17 FM patients and 17 controls. TRP, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and Interleukin-6 (IL-6) were measured. Additionally pain perception was monitored in the FM patients. FM patients and controls exhibited a decrease of TRP and KYN during TD. 5-HIAA levels also decreased in all controls and in 11 FM patients, but showed a marked increase in 6 FM patients. IL-6 significantly increased during TD in the patients, but not in the controls. Pain perception was not affected in the FM patients. These data demonstrate an altered TRP metabolism in a subgroup of FM patients, where the TD seems to activate 5-HT metabolism and IL-6 production. Our findings may have diagnostic as well as therapeutic implications in the field of fibromyalgia.

Adult↗
PubMed2002

Evidence for an altered tryptophan metabolism in fibromyalgia.

Fibromyalgia (FM) is a prevalent syndrome with chronic pain and a hypothesized underlying disturbance of the tryptophan (TRP) metabolism. We performed a tryptophan depletion (TD) test in 17 FM patients and 17 controls. TRP, 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), and interleukin-6 (IL-6) were measured. Additionally pain perception was monitored in the FM patients. FM patients and controls exhibited a decrease of TRP and KYN during TD. 5-HIAA levels also decreased in all controls and in 11 FM patients, but showed a marked increase in 6 FM patients. IL-6 significantly increased during TD in the patients, but not in the controls. Pain perception was not affected in the FM patients. These data demonstrate an altered TRP metabolism in a subgroup of FM patients, where the TD seems to activate 5-HT metabolism. Our findings may have diagnostic as well as therapeutic implications in the field of fibromyalgia.

Adult↗
PubMed1996

Molecular basis of alpha-methyltryptophan resistance in amt-1, a mutant of Arabidopsis thaliana with altered tryptophan metabolism.

A mutant of Arabidopsis thaliana, amt-1, was previously selected for resistance to growth inhibition by the tryptophan analog alpha-methyltryptophan. This mutant had elevated tryptophan levels and exhibited higher anthranilate synthase (AS) activity that showed increased resistance to feedback inhibition by tryptophan. In this study, extracts of the mutant callus exhibited higher AS activity than wild-type callus when assayed with either glutamine or ammonium sulfate as amino donor, thus suggesting that elevated AS activity in the mutant was due to an alteration in the alpha subunit of the enzyme. The mutant also showed cross-resistance to 5-methylanthranilate and 6-methylanthranilate and mapped to chromosome V at or close to ASA1 (a gene encoding the AS alpha subunit). ASA1 mRNA and protein levels were similar in mutant and wild-type leaf extracts. Levels of ASA1 mRNA and protein were also similar in callus cultures of mutant and wild type, although the levels in callus were higher than in leaf tissue. Sequencing of the ASA1 gene from amt-1 revealed a G to A transition relative to the wild-type gene that would result in the substitution of an asparagine residue in place of aspartic acid at position 341 in the predicted amino acid sequence of the ASA1 protein. The mutant allele in strain amt-1 has been renamed trp5-1.

Amino Acid Sequence↗
PubMed1998

Altered tryptophan metabolism in mice with herpes simplex virus encephalitis: increases in spinal cord quinolinic acid.

Mice infected with the herpes simplex virus, type-1, developed a paralysis which was associated with increased levels of the neurotoxin quinolinic acid (QUIN). The largest increases in QUIN were observed in the spinal cord with much smaller changes in the rostral forebrain or serum. The time course for the paralysis coincided with the increase in spinal cord QUIN, a maximal 40-fold elevation, at 7-10 days post infection. The time course suggested that the increases in QUIN were due to its local synthesis. Consistent with this possibility, herpes virus-infected mice had increased activities of indoleamine 2,3-dioxygenase and kynurenine hydroxylase (two key enzymes in QUIN formation), when compared to non-infected controls. Since QUIN is formed by activated macrophages, these new data are consistent with QUIN formation as part of the host response to a pathogen whose importance is discussed.

Animals↗
PubMed2006

Altered tryptophan metabolism in the brain of cystatin B-deficient mice: a model system for progressive myoclonus epilepsy.

PURPOSE: Progressive myoclonus epilepsy of the Unverricht-Lundborg type (EPM1) is a rare neurologic disorder, associated with mutations in the Cystatin B (Cstb) gene. Mice lacking Cstb, a cysteine protease inhibitor of the cathepsine family of proteases, provide a mammalian model for EPM1 by displaying similarly progressive ataxia, myoclonic seizures, and neurodegeneration. However, the linkage of Cstb deficit on the molecular level to pathologic features like myoclonic jerks or tonic-clonic seizures has remained unclear. We examined the tryptophan (TRP) metabolism, along the serotonin (5HT) and kynurenine (KYN) pathway in the brain of Cstb-deficient mice, in relation to their possible involvement in the seizure phenotype. METHODS: TRP and its metabolites, along the 5HT and KYN pathways, were assayed in brain tissue by high-pressure liquid chromatography (HPLC) with electrochemical detection. The inverted wire grid and mild handling tests were used for evaluation of ataxia and myoclonic activity. RESULTS: The Cstb-deficient mice had constitutively increased TRP, 5HT, and 5-hydroxyindole acetic acid (5HIAA) levels in the cerebral cortex and cerebellum and increased levels of KYN in the cerebellum. These neurochemical changes were accompanied with ataxia and an apparent myoclonic phenotype among the Cstb-deficient mice. CONCLUSIONS: Our findings suggest that secondary processes (i.e., overstimulation of serotoninergic transmission) on the cellular level, initiated by Cstb deficiency in specific brain regions, may be responsible for the myoclonic/seizure phenotype in EPM1.

Animals↗
PubMed1992

Alterations in tryptophan metabolism in the toxic oil syndrome and in the eosinophilia-myalgia syndrome.

The eosinophilia-myalgia syndrome (EMS) was associated with ingestion of L-tryptophan containing products and was accompanied by altered metabolism of L-tryptophan during the active phase. Many patients with EMS exhibited clinical and histopathological features similar to another epidemic, the toxic oil syndrome (TOS), associated with ingestion of adulterated rapeseed oil. We hypothesized that patients with TOS, like patients with EMS, may have had altered metabolism of L-tryptophan during the acute phase of the illness. Therefore, we quantitated the tryptophan metabolites, L-kynurenine and quinolinic acid, and we measured neopterin, a marker of interferon-gamma (IFN-gamma), in blood obtained during the acute phase of each syndrome. Patients with TOS or EMS had significantly higher L-kynurenine and quinolinic acid than healthy control subjects or rheumatic disease control subjects. Neopterin was also elevated in patients with untreated TOS and EMS, and correlated strongly with L-kynurenine and quinolinic acid. Our data suggest that indoleamine-2,3-dioxygenase (IDO), the rate limiting enzyme of the kynurenine pathway of L-tryptophan metabolism, was activated in both syndromes by cytokines including IFN-gamma, and that perhaps products of tryptophan metabolism played a role in the pathogenesis of EMS and TOS.

Arthritis, Rheumatoid↗
PubMed1987

Alteration of tryptophan metabolism in the synovial fluid of patients with rheumatoid arthritis and osteoarthritis.

Tryptophan, its metabolites and related enzyme activity in synovial fluid, blood and urine in patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were measured. The levels of tryptophan, kynurenine and anthranilic acid in the synovial fluid higher in RA were than in OA, whereas the xanthurenic acid level was equal in RA and OA. Indoleamine 2, 3-dioxygenase activity in the synovial membrane was higher in RA than in OA. 5-Hydroxytryptamine (5-HT) levels in the synovial fluid and the blood and the 5-hydroxyindole acetic acid (5-HIAA) level in the synovial fluid were essentially the same for both diseases. However, the 5-HIAA level in the serum of RA patients was higher than in those with OA, and the 5-HIAA level in the urine of RA patients was lower than in those with OA. In addition, monoamine oxidase-A and B activity in the synovial fluid of RA patients was decreased than in those with OA. These findings suggest that metabolism of tryptophan is altered in patients with RA.

Arthritis, Rheumatoid↗
PubMed1975

Vitamin B6 requirements of women using oral contraceptives.

Fifteen women who used combined estrogen-progestogen oral contraceptives and nine control women were given a vitamin B6-deficient diet for 4 weeks and the same diet supplemented with 0.8, 2.0, or 20.0 mg of pyridoxine hydrochloride for an additional 4 weeks. At weekly intervals a variety of indices of vitamin B6 nutrition were measured to determine rates of depletion and repletion. The tryptophan load test (2.0 g) was significantly different in the contraceptive users. However, other indices, including urinary cystathionine (3.0 g L-methionine load), urinary 4-pyridoxic acid, plasma phosphate, and erythrocyte alanine and aspartate aminotransferases, were not significantly different. Since altered tryptophan metabolism persisted in contraceptive users even when other indices of vitamin B6 nutrition were normal, we suggest that the use of oral contraceptives specifically affects tryptophan metabolism by some means other than through a vitamin B6 deficiency.

Adult↗
PubMed1978

Effects of portocaval anastomosis on behaviour and brain tryptophan metabolism.

The rat with portocaval anastomosis represents a convenient took for the investigation of (a) factors determining the availability of tryptophan to the brain and (b) the role, if any, that altered tryptophan metabolism may have in the development of hepatic encephalopathy. It was found that increases in brain tryptophan following anastomosis paralleled plasma free tryptophan rather than plasma total tryptophan regardless of whether or not correction for inhibition from amino acids competing with tryptophan for uptake into brain was applied. Nevertheless, while plasma free tryptophan exerts a major influence on brain tryptophan in both sham-operated and anastomosed rats, in the latter group brain tryptophan is raised further by some other mechanism. The anastomosed rat was also found to be behaviourally abnormal in a number of test situations. Thus, they were hypoactive during chronic exposure to an open-field and were less responsive to electric shock. Following the administration of tryptophan, sham-operated rats were also less active in an open-field and less responsive to electric shock when compared with saline-treated rats. Thus, anastomosed rats have behavioural abnormalities for which altered tryptophan metabolism might, to some extent, be responsible.

Animals↗
PubMed1994

Dose response and time course of alterations in tryptophan metabolism by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the most TCDD-susceptible and the most TCDD-resistant rat strain: relationship with TCDD lethality.

It has previously been shown that an increase in plasma free tryptophan and a consequent increase in brain serotonin (5-HT) metabolism may be associated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) lethality. In the present study we have studied the dose-response and time course relationships of these phenomena in the most TCDD-susceptible Long-Evans (Turku AB [L-E]; LD50 ca. 10 micrograms/kg) and the most TCDD-resistant Han/Wistar (Kuopio [H/W], LD50 > 7200 micrograms/kg) rat strains. Six days after exposure, there was a dose-related increase in brain 5-HT turnover and plasma free tryptophan in both male and female L-E rats. Pair-fed control rats did not exhibit changes in these parameters. The increases emerged in the dose range known to elicit lethality in L-E rats. Furthermore, the increases in plasma free tryptophan correlated well with the changes in body weight caused by TCDD. In contrast, in H/W rats no such increases in brain 5-HT metabolism or plasma free tryptophan were discernible. Similarly, body weight changes were minor in H/W rats despite almost 1000-fold greater doses of TCDD. Large neutral amino acids other than tryptophan were not markedly changed in the plasma of either rat strain. In attempts to identify the mechanism by which TCDD might affect tryptophan binding to albumin, some other physiological factors known to be carried by albumin were determined. Nonesterified fatty acids (NEFA) in the plasma were dose dependently elevated in male and female L-E rats and there was a moderate or good correlation (r = 0.654 for male and r = 0.731 for female rats) between this parameter and plasma free tryptophan. A moderate increase in plasma NEFA was also seen in pair-fed control rats. Bilirubin was dose dependently increased in the plasma of female L-E rats and there was a good correlation between plasma free tryptophan and total (r = 0.779) or conjugated (r = 0.825) bilirubin. The concentration of albumin tended to be suppressed in female L-E rats. The main tryptophan metabolizing enzyme, hepatic tryptophan pyrrolase, was inhibited in female L-E rats but not in male L-E rats or H/W rats of either gender. Moreover, in female L-E rats the time course for changes in plasma free tryptophan and in body weight was remarkably similar, with both effects emerging early (1 or 2 days) after TCDD exposure and showing progressive development thereafter until the last time point of 10 days.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids, Branched-Chain↗
PubMed1982

Alterations of tryptophan metabolism in a rat strain (Osborne-Mendel) predisposed to obesity.

1. Osborne-Mendel (O-M) rats displayed differences in brain and systemic tryptophan metabolism. O-M rats had decreased brainstem tryptophan-5-hydroxylase activity and decreased serotonin (5-HT) levels as compared to Sprague-Dawley rats. However, brain tryptophan levels were actually increased in O-M rats. Norepinephrine, dopamine and 5-hydroxyindole-3-acetic acid levels were not different between strains. 2. Pineal serotonin levels were increased in O-M rats. 3. Liver tryptophan 2,3-dioxygenase activity was increased in O-M rats while tyrosine aminotransferase activity was not different between strains. 4. Total blood cholesterol was decreased in O-M rats while triglycerides, free fatty acids and albumin was not different between strains. Total serum tryptophan was not different between strains while O-M rats had an increased level of free (unbound) tryptophan.

Animals↗
PubMed2003

Possible alteration of tryptophan metabolism following repeated administration of sertraline in the rat brain.

The levels of tryptophan and the serotonin (5-HT) turnover were examined in various brain regions of rats after single or repeated treatment with the selective 5-HT uptake inhibitor, sertraline. A single administration of sertraline (10mg/kg, i.p.) increased tryptophan and 5-HT levels in all the brain regions investigated. The levels of 5-hydroxyindolacetic acid (5-HIAA) decreased in various brain regions. The 5-HIAA/5-HT ratio as turnover index was significantly decreased by a single administration of sertraline in all the brain regions investigated. Daily treatment with sertraline (10mg/kg) for 21 days did not affect tryptophan and 5-HT levels in various brain regions 1h after last injection. The 5-HT turnover was not changed in any of the brain regions investigated by a repeated administration of sertraline. In conclusion, the data show that the increase in tryptophan levels and the decrease in 5-HT turnover in rat brain are attenuated by repeated treatment of sertraline.

Animals↗