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Post-synthetic modification of tryptophan containing peptides via NIS mediation.

A new efficient method was developed to provide modified tryptophan peptides through NIS (N-iodosuccinimide) mediated N2-selective coupling of a Trp unit with 1,2,3-triazoles, of which, the preliminary spectral properties were also studied.

Tryptophan catabolism in acute exacerbations of chronic obstructive pulmonary disease.

INTRODUCTION: Exacerbations are a leading cause of morbidity in COPD. The objective of this study was to identify metabolomic biomarkers of … 31 analytes that differed in the AECOPD cases between day 0 and day 30 (false discovery rate: 5%). Tryptophan was decreased at day 0 of AECOPD compared to controls corresponding to an increase in indoleamine 2,3-dioxygenase activity. CONCLUSION: Patients with AECOPD have a unique metabolomic signature that includes a decrease in tryptophan levels consisten …

High-throughput fluorescence-based screening assays for tryptophan-catabolizing enzymes.

Indoleamine 2,3-dioxygenase (IDO1) and tryptophan 2,3-dioxygenase (TDO) are two structurally different enzymes that have a different tissue distribution and physiological roles, but both catalyze the conversion of tryptophan to N-formylkynurenine (NFK). IDO1 has been clinically validated as a small-molecule drug target for cancer, while preclinical studies indicate that TDO may be a target for cancer immunotherapy and neurodegenerative disease. We have developed a high-throughput screening assay for IDO1 and TDO based on a novel chemical probe, NFK Green, that reacts specifically with NFK to f…

Refractory idiopathic thrombocytopenic purpura treated with immunoadsorption using tryptophan column.

The treatment of refractory idiopathic thrombocytopenia in adult is a challenge. Here we report successful treatment of an adult ITP patient with immunoadsorption using tryptophan column who were refractory to steroids, splenectomy, eltrombopag and various immunosuppressive medications.

Blood chemistry, hematology and tryptophan level in cerebral malaria children.

BACKGROUND: Cerebral malaria is a deadly complication of P. falciparum infection, yet its pathogenesis remains incompletely understood. OBJECTIVE: The blood chemistry, hematology, protein and tryptophan levels in the cerebrospinal fluid (CSF) of cerebral malaria children were investigated. METHODS: Fifteen children (2.44 +/- 0.25 yr) diagnosed with cerebral malaria were used for this study. The control subjects consist of healthy and malaria-free children (2.50 +/- 0.16 yr). Two ml of blood were collected from each child between 0830 h and 0930 h. Blood chemistry and hematological parameters…

Defective tryptophan catabolism underlies inflammation in mouse chronic granulomatous disease.

Half a century ago, chronic granulomatous disease (CGD) was first described as a disease fatally affecting the ability of children to surviv … reasons for the exaggerated inflammatory response. Here we show that a superoxide-dependent step in tryptophan metabolism along the kynurenine pathway is blocked in CGD mice with lethal pulmonary aspergillosis, leading to unrestrained Vgamma1(+) gammadelta T-cell reactivity, dominant production of interleukin (IL)-17, defective regulatory T-cell activity and …

Tryptophan metabolism via serotonin in rats with hexachlorobenzene experimental porphyria.

One of the three pathways for the metabolisation of dietary tryptophan is the formation of serotonin. Tryptophan hydroxylase catalyses the formation of 5-hydroxytryptophan, the first and regulatory step of this biosynthesis. The aim of the present work is to study alterations in this tryptophan metabolism in rats with experimental Porphyria Cutanea Tarda induced by hexachlorobenzene. With this purpose, the content of tryptophan and its metabolites related to the serotonin pathway are determined by HPLC techniques, in tissues (brain, liver and gut) and in fluids (blood, plasma and urine) of con…

Activation of beta2- and beta3-adrenergic receptors increases brain tryptophan.

Brain tryptophan concentrations are increased by various stressful treatments, an effect that can be prevented by beta-adrenoceptor antagonists. This study aimed to determine the beta-adrenergic subtype responsible for the tryptophan response. Male CD-1 mice received intraperitoneal injections of nonselective and subtype-selective beta-adrenergic antagonists 20 min before subtype-selective beta-agonists. Selected brain regions were dissected for analysis of tryptophan content by high-performance liquid chromatography with electrochemical detection. The beta(2)-selective agonist clenbuterol (0.…

Association between tryptophan hydroxylase gene polymorphism (A218C) and schizophrenic disorders.

The human tryptophan hydroxylase (TPH) gene, the rate-limiting enzyme in serotonin biosynthesis, was localized on human chromosome 11p14-p15.3. Variation within intron 7 of the TPH gene was found to influence serotonin metabolism in the brain. To explore the possible role of TPH in the pathogenesis of schizophrenic disorders, we genotyped the TPH A218C polymorphism in 196 schizophrenic patients and 251 controls. The results demonstrated that genotype distribution was significantly different between schizophrenic patients and control subjects (P=0.002). No association was found between TPH geno…

Tryptophan levels, excessive exercise, and nutritional status in anorexia nervosa.

OBJECTIVE: It has been hypothesized that reduced dietary availability of tryptophan may be the cause of impaired serotonin activity in underweight anorexics. The study reported here evaluated the relationship between tryptophan availability in the blood and nutritional status in anorexia nervosa. METHODS: The total amount of tryptophan and the ratio between tryptophan and other large neutral amino acids (TRP/LNAA) were assessed in a sample of 16 starving anorexic patients. Body weight and composition and energy intake were evaluated in all patients. All subjects also completed self-reported q…

Influence of trait hostility on tryptophan depletion-induced laboratory aggression.

Previous research has indicated that laboratory aggression in men increases after temporarily reducing the synthesis and neurotransmission of serotonin (5-HT) in the brain using the plasma L-tryptophan (Trp) depletion technique. Further research indicates that male subjects selected for high trait hostility are particularly prone to increased aggression following plasma Trp depletion. In a recent study of laboratory aggression in male control subjects, we demonstrated that laboratory aggression increased following ingestion of a Trp-depleting beverage, but not after ingestion of a Trp-containi…

Measurement of tryptophan hydroxylase mRNA levels by competitive RT-PCR.

Tryptophan hydroxylase (TPH) is the rate limiting enzyme in serotonin biosynthesis [D.G. Grahame-Smith, Tryptophan hydroxylation in brain, Biochem. Biophys. Res. Commun. 16 (1964) 586-592 [19]]. As such, the TPH gene is a likely target for modulation of serotonergic function, which has been associated with several psychiatric disorders [E.C. Azmitia, P.M. Whitaker-Azmitia, Awakening the sleeping giant: anatomy and plasticity of the brain serotonergic system, J. Clin. Psychiatry 52 (12, Suppl.) (1991) 4-16 [1]; R.P. Hart, R. Yang, L.A. Riley., T.L. Green, Post-transcriptional control of tryptop…

Characterization of recombinant mouse tryptophan hydroxylase expressed in Escherichia coli.

Recombinant mouse tryptophan hydroxylase (TPH) was expressed in large quantities in Escherichia coli strain MC 1061, using a bacterial expression vector, pKS, containing the full coding region of mouse TPH. Specific polyclonal antiserum to the subunit of the recombinant mouse TPH was produced in rabbit by injecting the TPH band cut from SDS-polyacrylamide slab gels. The resultant antiserum recognized a single identical protein band (MW = 54,000) from rat dorsal raphe area, pineal gland, and brain stem by Western blot analysis. The specific activity of recombinant mouse TPH obtained was equival…

[L-tryptophan-associated chronic eosinophilia-myalgia syndrome treated with cyclosporin].

After 2 weeks of ingestion of 130 g L-Tryptophan a 52 year old female develops an Eosinophilia Myalgia Syndrome with acute onset of deep venous thrombosis of forearm and possible initial cardiac manifestation featuring intermittent sinustachykardia. This is followed by a severe chronic disease (follow-up 15 months) with diffuse scleroderma and sensomotoric polyneuropathia. The deep muscle biopsy-specimen shows mononuclear infiltration of fascia and interstitial myositis with rare eosinophils. A blood eosinophilia (900/ul) occurs only in the initial acute onset of the illness. Plasma level of K…

Hypercapnic respiratory failure due to L-tryptophan-induced eosinophilic polymyositis.

A 24-year-old man presenting with fever, rash, and myalgias subsequently developed hypercapnic respiratory failure and severe limb muscle weakness. Muscle biopsy revealed eosinophilic myositis, due to the ingestion of large quantities of L-tryptophan as a dietary supplement. Complete recovery occurred with corticosteroid administration. Significant involvement of the respiratory muscles can be a predominant feature of this newly described disease entity.

Targeting Tryptophan Metabolism for Tuberculosis Biomarkers and Host-Directed Therapy.

Greater understanding of the role of tryptophan metabolism in the immune response to tuberculosis (TB) has provided promising avenues to explore new diagnostic and therapeutic modalities. Animal and human studies have demonstrated that host indoleamine 2,3-dioxygenase 1 (IDO1) is upregulated in response to infection with Mycobacterium tuberculosis, resulting in increased tryptophan metabolism to kynurenine. In TB disease, this is evidenced by elevation of the plasma kynurenine to tryptophan ratio, which is reversed with effective TB treatment, thus showing utility as a potential diagnostic and…

Традиционное профилирование триптофана у пациентов с множественным склерозом, которые лечились острелизумабом.

ВВЕДЕНИЕ: метаболизм Л-Триптофана (трп) нарушается при различных хронических провокационных патологиях, включая множественный склероз (МС). Процесс обработки трпов опирается на три метаболических пути, а именно: Kynurenin, Serotonin и Indole. Принимающая микробиота оказывает значительное воздействие на метаболизм Trp, главным образом в силу того, что она отвечает за производство индоловых метаболитов, и, во-вторых, в результате формирования путей как кинурейнина, так и серотонина. Патологические условия и лекарственные препараты могут вызвать изменения в микробном популяции, что может привести

Совпадение в аннотации оригинала
INTRODUCTION: L-Tryptophan (Trp) metabolism is impaired across various chronic inflammatory pathologies, including Multiple Sclerosis (MS). Trp processing relies on three metabolic routes, namely Kynurenine, Serotonin and Indole pathways. The host microbiota significantly impacts Trp metabolism, primarily by being responsible for Indole metabolites productio…

Blocking Tryptophan Catabolism Reduces Triple-Negative Breast Cancer Invasive Capacity.

TDO2 is more highly expressed than the nonhomologous TRP-catabolizing enzyme IDO1 in TNBC. We find that TDO2 knockdown can lead to a compensatory increase in IDO1. Therefore, we tested a newly developed TDO2/IDO1 dual inhibitor and found that it decreases TRP catabolism, anchorage-independent survival, and invasive capacity.

Ultraviolet Superradiance from Mega-Networks of Tryptophan in Biological Architectures.

Networks of tryptophan (Trp)─an aromatic amino acid with strong fluorescence response─are ubiquitous in biological systems, forming diverse architectures in transmembrane proteins, cytoskeletal filaments, subneuronal elements, photoreceptor complexes, virion capsids, and other cellular structures. We analyze the cooperative effects induced by ultraviolet (UV) excitation of several biologically relevant Trp mega-networks, thus giving insights into novel mechanisms for cellular signaling and control. Our theoretical analysis in the single-excitation manifold predicts the formation of strongly su…