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Tryptophan catabolism

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https://www.readbyqxmd.com/read/27891058/ido2-a-pathogenic-mediator-of-inflammatory-autoimmunity
#1
REVIEW
Lauren M F Merlo, Laura Mandik-Nayak
Indoleamine 2,3-dioxygenase 2 (IDO2), a homolog of the better-studied tryptophan-catabolizing enzyme IDO1, is an immunomodulatory molecule with potential effects on various diseases including cancer and autoimmunity. Here, we review what is known about the direct connections between IDO2 and immune function, particularly in relationship to autoimmune inflammatory disorders such as rheumatoid arthritis and lupus. Accumulating evidence indicates that IDO2 acts as a pro-inflammatory mediator of autoimmunity, with a functional phenotype distinct from IDO1...
2016: Clinical Medicine Insights. Pathology
https://www.readbyqxmd.com/read/27886064/probiotic-supplements-beneficially-affect-tryptophan-kynurenine-metabolism-and-reduce-the-incidence-of-upper-respiratory-tract-infections-in-trained-athletes-a-randomized-double-blinded-placebo-controlled-trial
#2
Barbara Strasser, Daniela Geiger, Markus Schauer, Johanna M Gostner, Hannes Gatterer, Martin Burtscher, Dietmar Fuchs
BACKGROUND: Prolonged intense exercise has been associated with transient suppression of immune function and an increased risk of infections. In this context, the catabolism of amino acid tryptophan via kynurenine may play an important role. The present study examined the effect of a probiotic supplement on the incidence of upper respiratory tract infections (URTI) and the metabolism of aromatic amino acids after exhaustive aerobic exercise in trained athletes during three months of winter training...
November 23, 2016: Nutrients
https://www.readbyqxmd.com/read/27871872/biotechnological-production-of-aromatic-compounds-of-the-extended-shikimate-pathway-from-renewable-biomass
#3
Jin-Ho Lee, Volker F Wendisch
Aromatic chemicals that contain an unsaturated ring with alternating double and single bonds find numerous applications in a wide range of industries, e.g. paper and dye manufacture, as fuel additives, electrical insulation, resins, pharmaceuticals, agrochemicals, in food, feed and cosmetics. Their chemical production is based on petroleum (BTX; benzene, toluene, and xylene), but they can also be obtained from plants by extraction. Due to petroleum depletion, health compliance, or environmental issues such as global warming, the biotechnological production of aromatics from renewable biomass came more and more into focus...
November 18, 2016: Journal of Biotechnology
https://www.readbyqxmd.com/read/27870896/m30-antagonizes-indoleamine-2-3-dioxygenase-activation-and-neurodegeneration-induced-by-corticosterone-in-the-hippocampus
#4
Chun-Sing Lam, George Lim Tipoe, Johnny Kong-Ching Wong, Moussa B H Youdim, Man-Lung Fung
Monoamine oxidases (MAO), downstream targets of glucocorticoid, maintain the turnover and homeostasis of monoamine neurotransmitters; yet, its pathophysiological role in monoamine deficiency, oxidative stress and neuroinflammation remains controversial. Protective effects of M30, a brain selective MAO inhibitor with iron-chelating antioxidant properties, have been shown in models of neurodegenerative diseases. This study aims to examine the neuroprotective mechanism of M30 against depressive-like behavior induced by corticosterone (CORT)...
2016: PloS One
https://www.readbyqxmd.com/read/27866207/post-stroke-fatigue-may-be-associated-with-the-promoter-region-of-a-monoamine-oxidase-a-gene-polymorphism
#5
Smi Choi-Kwon, Mihye Ko, Sang-Eun Jun, Juhan Kim, Kyung-Hee Cho, Hyun-Wook Nah, Hasup Song, Jong S Kim
BACKGROUND: Post-stroke fatigue (PSF) is a common sequela of stroke. Despite reports of serotonergic involvement in the etiology of PSF, the potential contribution of serotonergic genes in the development of PSF needs to be investigated. METHODS: A total of 373 patients, who experienced ischemic stroke for PSF, were evaluated 3 months after the stroke. PSF was assessed using the Fatigue Severity Scale. The genomic DNA collected and stored in a -70°C freezer was genotyped for 6 polymorphisms in genes associated with serotonin synthesis (tryptophan hydroxylase 1 (TPH1) A218C, TPH2 rs10879355, and TPH2 rs4641528), transport (the promoter region of the serotonin transporter protein), and catabolism (the 30-bp functional variable number tandem repeat) polymorphism in the promoter region of monoamine oxidase A (MAO-A)...
November 19, 2016: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/27861556/antioxidant-properties-of-kynurenines-density-functional-theory-calculations
#6
Aleksandr V Zhuravlev, Gennady A Zakharov, Boris F Shchegolev, Elena V Savvateeva-Popova
Kynurenines, the main products of tryptophan catabolism, possess both prooxidant and anioxidant effects. Having multiple neuroactive properties, kynurenines are implicated in the development of neurological and cognitive disorders, such as Alzheimer's, Parkinson's, and Huntington's diseases. Autoxidation of 3-hydroxykynurenine (3HOK) and its derivatives, 3-hydroxyanthranilic acid (3HAA) and xanthommatin (XAN), leads to the hyperproduction of reactive oxygen species (ROS) which damage cell structures. At the same time, 3HOK and 3HAA have been shown to be powerful ROS scavengers...
November 2016: PLoS Computational Biology
https://www.readbyqxmd.com/read/27853989/proposed-recommendations-for-diagnosing-and-managing-individuals-with-glutaric-aciduria-type-i-second-revision
#7
REVIEW
Nikolas Boy, Chris Mühlhausen, Esther M Maier, Jana Heringer, Birgit Assmann, Peter Burgard, Marjorie Dixon, Sandra Fleissner, Cheryl R Greenberg, Inga Harting, Georg F Hoffmann, Daniela Karall, David M Koeller, Michael B Krawinkel, Jürgen G Okun, Thomas Opladen, Roland Posset, Katja Sahm, Johannes Zschocke, Stefan Kölker
Glutaric aciduria type I (GA-I; synonym, glutaric acidemia type I) is a rare inherited metabolic disease caused by deficiency of glutaryl-CoA dehydrogenase located in the catabolic pathways of L-lysine, L-hydroxylysine, and L-tryptophan. The enzymatic defect results in elevated concentrations of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutaryl carnitine in body tissues, which can be reliably detected by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines)...
November 16, 2016: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/27819068/the-kynurenine-tryptophan-ratio-and-glioblastoma-patients-treated-with-hsppc-96-vaccine
#8
Alicia Lenzen, Lijie Zhai, Kristen L Lauing, Galina Gritsina, Erik Ladomersky, Matthew Genet, C David James, Orin Bloch, Derek A Wainwright
The discovery that immunotherapy is a clinically-relevant approach for the treatment of malignant tumors is revolutionizing patient care. In adults diagnosed with glioblastoma (GBM), an aggressive and incurable primary brain tumor, autologous HSPPC-96 vaccination provides a significant increase in overall survival. However, all GBM patients eventually succumb to their disease, providing rationale for discovering new methods that proactively identify individuals that will respond, optimally. Of the immunosuppressive mediators that contribute to the inhibition of productive tumor immunity, indoleamine 2,3 dioxygenase 1 (IDO1), a rate-limiting enzyme that catabolizes tryptophan (Trp) into kynurenine (Kyn), has been demonstrated to be expressed at elevated levels in patients with malignant glioma...
September 2016: Immunotherapy (Los Angeles, Calif.)
https://www.readbyqxmd.com/read/27810899/a-pitcher-and-catcher-mechanism-drives-endogenous-substrate-isomerization-by-a-dehydrogenase-in-kynurenine-metabolism
#9
Yu Yang, Ian Davis, Uyen Ha, Yifan Wang, Inchul Shin, Aimin Liu
Aldehyde dehydrogenase typically perform oxidation of aldehydes to their corresponding carboxylic acid while reducing NAD(P)+ to NAD(P)H via covalent catalysis mediated by an active-site cysteine residue. One member of this superfamily, the enzyme 2-aminomuconate-6-semialdehyde dehydrogenase (AMSDH), is a component of the kynurenine pathway which catabolizes tryptophan in mammals and certain bacteria. AMSDH catalyzes the NAD+-dependent oxidation of 2-aminomuconate semialdehyde to 2-aminomuconate. We recently determined the first crystal structure of AMSDH and several catalytic cycle intermediates...
November 3, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27773992/the-kynurenine-pathway-is-a-double-edged-sword-in-immune-privileged-sites-and-in-cancer-implications-for-immunotherapy
#10
Jean-Pierre Routy, Bertrand Routy, Gina M Graziani, Vikram Mehraj
The term "immune privilege" was originally coined to describe the suppression of inflammatory responses within organs protected by anatomic barriers, ie, the eyes, brain, placenta, and testes. However, cellular and metabolic processes, which orchestrate immune responses, also control inflammation within these sites. Our current understanding of tolerogenic mechanisms has extended the definition of immune privilege to include hair follicles, the colon, and cancer. By catabolizing tryptophan, cells expressing the enzyme indoleamine-2,3-dioxygenase produce kynurenine metabolites, which orchestrate local and systemic responses to control inflammation, thus maintaining immune privilege...
2016: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/27771694/activation-of-tryptophan-and-phenylalanine-catabolism-in-the-remission-phase-of-allergic-contact-dermatitis-a-pilot-study
#11
Auksė Zinkevičienė, Denis Kainov, Irutė Girkontaitė, Eglė Lastauskienė, Violeta Kvedarienė, Yu Fu, Simon Anders, Vidya Velagapudi
BACKGROUND: Allergic contact dermatitis (ACD) is an inflammatory skin disease caused by repeated skin exposure to contact allergens. The severity and duration of this disease are associated with many different factors. Some of these factors may represent markers for monitoring disease activity and the individual response to an intervention. METHODS: We used a targeted metabolomics approach to find such factors in the serum of individuals with ACD. Metabolomics profiles were examined and compared in the acute phase of the disease and also in the absence of disease activity...
October 22, 2016: International Archives of Allergy and Immunology
https://www.readbyqxmd.com/read/27729784/tryptophan-catabolism-in-acute-exacerbations-of-chronic-obstructive-pulmonary-disease
#12
Makedonka Gulcev, Cavan Reilly, Timothy J Griffin, Corey D Broeckling, Brian J Sandri, Bruce A Witthuhn, Shane W Hodgson, Prescott G Woodruff, Chris H Wendt
INTRODUCTION: Exacerbations are a leading cause of morbidity in COPD. The objective of this study was to identify metabolomic biomarkers of acute exacerbations of COPD (AECOPD). METHODS: We measured metabolites via mass spectrometry (MS) in plasma drawn within 24 hours of admission to the hospital for 33 patients with an AECOPD (day 0) and 30 days later and for 65 matched controls. Individual metabolites were measured via selective reaction monitoring with mass spectrometry...
2016: International Journal of Chronic Obstructive Pulmonary Disease
https://www.readbyqxmd.com/read/27705910/indoleamine-2-3-dioxygenase-regulates-anti-tumor-immunity-in-lung-cancer-by-metabolic-reprogramming-of-immune-cells-in-the-tumor-microenvironment
#13
Cara C Schafer, Yong Wang, Kenneth P Hough, Anandi Sawant, Stefan C Grant, Victor J Thannickal, Jaroslaw Zmijewski, Selvarangan Ponnazhagan, Jessy S Deshane
Indoleamine 2,3-dioxygenase (IDO) has been implicated in immune evasion by tumors. Upregulation of this tryptophan (Trp)-catabolizing enzyme, in tumor cells and myeloid-derived suppressor cells (MDSCs) within the tumor microenvironment (TME), leads to Trp depletion that impairs cytotoxic T cell responses and survival; however, exact mechanisms remain incompletely understood. We previously reported that a combination therapy of gemcitabine and a superoxide dismutase mimetic promotes anti-tumor immunity in a mouse model of lung cancer by inhibiting MDSCs, enhancing polyfunctional response of CD8+ memory T cells, and extending survival...
September 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27695641/cell-intrinsic-factors-modulate-the-effects-of-ifn%C3%AE-on-the-development-of-chlamydia-trachomatis
#14
Shardulendra Sherchand, Joyce A Ibana, Alison J Quayle, Ashok Aiyar
Chlamydia trachomatis is an obligate intracellular bacterial pathogen that cannot synthesize several amino acids, including tryptophan. Rather, C. trachomatis acquires these essential metabolites from its human host cell. Chlamydial dependence on host-provided tryptophan underlies a major host defense mechanism against the bacterium; namely, the induction of the host tryptophan-catabolizing enzyme, indoleamine 2,3- dioxygenase (IDO1) by interferon gamma (IFNγ), which leads to eradication of C. trachomatis by tryptophan starvation...
August 2016: Journal of Bacteriology & Parasitology
https://www.readbyqxmd.com/read/27695127/respiratory-syncytial-virus-infected-mesenchymal-stem-cells-regulate-immunity-via-interferon-beta-and-indoleamine-2-3-dioxygenase
#15
Michael B Cheung, Viviana Sampayo-Escobar, Ryan Green, Martin L Moore, Subhra Mohapatra, Shyam S Mohapatra
Respiratory syncytial virus (RSV) has been reported to infect human mesenchymal stem cells (MSCs) but the consequences are poorly understood. MSCs are present in nearly every organ including the nasal mucosa and the lung and play a role in regulating immune responses and mediating tissue repair. We sought to determine whether RSV infection of MSCs enhances their immune regulatory functions and contributes to RSV-associated lung disease. RSV was shown to replicate in human MSCs by fluorescence microscopy, plaque assay, and expression of RSV transcripts...
2016: PloS One
https://www.readbyqxmd.com/read/27689750/prolongation-of-kidney-allograft-survival-regulated-by-indoleamine-2-3-dioxygenase-in-immature-dendritic-cells-generated-from-recipient-type-bone-marrow-progenitors
#16
Ning Na, Yun Luo, Daqiang Zhao, Shicong Yang, Liangqing Hong, Heng Li, Bin Miao, Jiang Qiu
Immature dendritic cells (iDCs) are bone marrow-derived professional antigen-presenting cells, exhibit very low levels of the co-stimulatory molecules CD80 (B7-1), CD86 (B7-2), and CD40 and major histocompatibility complex (MHC) class II and play a critical role in triggering antigen-specific immunotolerance. The enzyme indoleamine 2, 3-dioxygenase (IDO) is a cytosolic tryptophan catabolism rate-limiting step enzyme. IDO secreted by DCs shows an association with the suppression of T-cell responses and promotion of tolerance...
September 27, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27677162/immune-tolerance-properties-of-the-testicular-tissue-as-a-viral-sanctuary-site-in-art-treated-hiv-infected-adults
#17
Mohammad-Ali Jenabian, Cecilia T Costiniuk, Vikram Mehraj, Feras M Ghazawi, Rémi Fromentin, Joëlle Brousseau, Pierre Brassard, Maud Bélanger, Petronela Ancuta, Reina Bendayan, Nicolas Chomont, Jean-Pierre Routy
OBJECTIVE: HIV persistence in long-lived infected cells and in anatomical sanctuary sites are major hurdles to HIV eradication. Testicular tissue may represent a significant viral sanctuary site as it constitutes an immunologically-privileged compartment. We assessed immuno-tolerance properties of the testicular tissue in individuals receiving suppressive ART. DESIGN AND METHODS: Testicular tissue and matched blood samples were collected from 6 virally suppressed adults and 10 HIV-uninfected controls prior to gender reassignment surgery...
September 24, 2016: AIDS
https://www.readbyqxmd.com/read/27568378/astrocytic-and-neuronal-localization-of-kynurenine-aminotransferase-2-in-the-adult-mouse-brain
#18
Judit Herédi, Anikó Magyariné Berkó, Ferenc Jankovics, Tokuko Iwamori, Naoki Iwamori, Etsuro Ono, Szatmár Horváth, Zsolt Kis, József Toldi, László Vécsei, Levente Gellért
During catabolism of tryptophan through the kynurenine (KYN) pathway, several endogenous metabolites with neuromodulatory properties are produced, of which kynurenic acid (KYNA) is one of the highest significance. The causal role of altered KYNA production has been described in several neurodegenerative and neuropsychiatric disorders (e.g., Parkinson's disease, Huntington's disease, schizophrenia) and therefore kynurenergic manipulation with the aim of therapy has recently been proposed. Conventionally, KYNA is produced from its precursor L-KYN with the aid of the astrocytic kynurenine aminotransferase-2 (KAT-2) in the murine brain...
August 27, 2016: Brain Structure & Function
https://www.readbyqxmd.com/read/27565863/influence-of-core-body-temperature-on-tryptophan-metabolism-kynurenines-and-estimated-ido-activity-in-critically-ill-patients-receiving-target-temperature-management-following-cardiac-arrest
#19
Joerg C Schefold, Nora Fritschi, Gerhard Fusch, Aldin Bahonjic, Wolfram Doehner, Stephan von Haehling, Rene Pschowski, Christian Storm, Tim Schroeder
BACKGROUND/AIMS: Temperature control improves neurological prognosis in comatose cardiac arrest (CA) survivors. Previous reports demonstrate that most affected patients show signs of significant systemic inflammation. In an effort to better characterize potential temperature-related effects on key inflammatory pathways, we investigate the course of Tryptophan (Trp) levels, Tryptophan catabolites (including kynurenines) and indoleamine-2,3-dioxygenase (IDO)-activity in post CA patients...
October 2016: Resuscitation
https://www.readbyqxmd.com/read/27513176/synthesis-of-the-reported-pyranonaphthoquinone-structure-of-the-indoleamine-2-3-dioxygenase-inhibitor-annulin-b-by-regioselective-diels-alder-reaction
#20
Martyn Inman, Catarina Carvalho, William Lewis, Christopher J Moody
Annulin B, isolated from the marine hydroid isolated from Garveia annulata, is a potent inhibitor of the tryptophan catabolizing enzyme indoleamine-2,3-dioxygenase (IDO). A synthesis of the reported pyranonaphthoquinone structure is described, in which the key step is a regioselective Diels-Alder reaction between a pyranobenzoquinone dienophile and a silyl ketene acetal diene.
September 2, 2016: Journal of Organic Chemistry
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