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Tryptophan catabolism

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https://www.readbyqxmd.com/read/28344890/suppression-of-indoleamine-2-3-dioxygenase-1-expression-by-promoter-hypermethylation-in-er-positive-breast-cancer
#1
Dyah L Dewi, Soumya R Mohapatra, Saioa Blanco Cabañes, Isabell Adam, Luis F Somarribas Patterson, Bianca Berdel, Masroor Kahloon, Loreen Thürmann, Stefanie Loth, Katharina Heilmann, Dieter Weichenhan, Oliver Mücke, Ines Heiland, Pauline Wimberger, Jan Dominik Kuhlmann, Karl-Heinz Kellner, Sarah Schott, Christoph Plass, Michael Platten, Clarissa Gerhäuser, Saskia Trump, Christiane A Opitz
Kynurenine formation by tryptophan-catabolic indoleamine-2,3-dioxygenase 1 (IDO1) plays a key role in tumor immune evasion and inhibition of IDO1 is efficacious in preclinical models of breast cancer. As the response of breast cancer to immune checkpoint inhibitors may be limited, a better understanding of the expression of additional targetable immunomodulatory pathways is of importance. We therefore investigated the regulation of IDO1 expression in different breast cancer subtypes. We identified estrogen receptor α (ER) as a negative regulator of IDO1 expression...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28314892/abnormal-kynurenine-pathway-of-tryptophan-catabolism-in-cardiovascular-diseases
#2
REVIEW
Ping Song, Tharmarajan Ramprasath, Huan Wang, Ming-Hui Zou
Kynurenine pathway (KP) is the primary path of tryptophan (Trp) catabolism in most mammalian cells. The KP generates several bioactive catabolites, such as kynurenine (Kyn), kynurenic acid (KA), 3-hydroxykynurenine (3-HK), xanthurenic acid (XA), and 3-hydroxyanthranilic acid (3-HAA). Increased catabolite concentrations in serum are associated with several cardiovascular diseases (CVD), including heart disease, atherosclerosis, and endothelial dysfunction, as well as their risk factors, including hypertension, diabetes, obesity, and aging...
March 17, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28264972/synovial-fibroblasts-selectively-suppress-th1-cell-responses-through-ido1-mediated-tryptophan-catabolism
#3
Lars-Oliver Tykocinski, Anna M Lauffer, Antonia Bohnen, Nathalie-Christin Kaul, Stefan Krienke, Theresa Tretter, Isabell Adam, Soumya R Mohapatra, Philippe Saikali, Max Löhning, Michel Neidhart, Steffen Gay, Iris Oezen, Michael Platten, Christiane A Opitz, Hanns-Martin Lorenz
The development of rheumatoid arthritis (RA) is linked to functional changes in synovial fibroblasts (SF) and local infiltration of T lymphocytes. Fibroblasts possess the capacity to suppress T cell responses, although the molecular mechanisms of this suppression remain incompletely understood. In this study, we aimed to define the mechanisms by which noninflammatory SF modulate Th cell responses and to determine the immunosuppressive efficacy of RASF. Hence, the influence of SF from osteoarthritis or RA patients on total Th cells or different Th cell subsets of healthy donors was analyzed in vitro...
March 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28250737/kynurenine-pathway-metabolism-and-neuroinflammatory-disease
#4
REVIEW
Nady Braidy, Ross Grant
Immune-mediated activation of tryptophan (TRYP) catabolism via the kynurenine pathway (KP) is a consistent finding in all inflammatory disorders. Several studies by our group and others have examined the neurotoxic potential of neuroreactive TRYP metabolites, including quinolinic acid (QUIN) in neuroinflammatory neurological disorders, including Alzheimer's disease (AD), multiple sclerosis, amylotropic lateral sclerosis (ALS), and AIDS related dementia complex (ADC). Our current work aims to determine whether there is any benefit to the affected individuals in enhancing the catabolism of TRYP via the KP during an immune response...
January 2017: Neural Regeneration Research
https://www.readbyqxmd.com/read/28238935/tryptophan-and-purine-metabolites-are-consistently-upregulated-in-the-urinary-metabolome-of-patients-diagnosed-with-gestational-diabetes-mellitus-throughout-pregnancy-a-longitudinal-metabolomics-study-of-chinese-pregnant-women-part-2
#5
Kai P Law, Ting-Li Han, Xun Mao, Hua Zhang
BACKGROUND: Gestational diabetes mellitus (GDM) is a pathological state of glucose intolerance associated with adverse pregnancy outcomes and an increased risk of developing maternal type 2 diabetes later in life. The mechanisms underlying GDM development are not fully understood. We examined the pathophysiology of GDM through comprehensive metabolic profiling of maternal urine, using participants from a longitudinal cohort of normal pregnancies and pregnancies complicated by GDM. METHODS: Based on ultra-performance liquid chromatography/hybrid quadrupole time-of-flight mass spectrometry, an untargeted metabolomics study was performed to explore the differences in the urinary metabolome of GDM cases and healthy controls over the course of pregnancy...
February 24, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28218981/the-genetic-architecture-of-amino-acids-dissection-by-association-and-linkage-analysis-in-maize
#6
Min Deng, Dongqin Li, Jingyun Luo, Yingjie Xiao, Haijun Liu, Qingchun Pan, Xuehai Zhang, Minliang Jin, Mingchao Zhao, Jianbing Yan
Amino acids are both constituents of proteins, providing the essential nutrition for humans and animals, and signaling molecules regulating the growth and development of plants. Most cultivars of maize are deficient in essential amino acids such as lysine and tryptophan. Here, we measured the levels of 17 different total amino acids, and created 48 derived traits in mature kernels from a maize diversity inbred collection and three recombinant inbred line (RIL) populations. By GWAS, 247 and 281 significant loci were identified in two different environments, 5...
February 20, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28196863/conformational-changes-in-the-activation-loop-of-mitochondrial-glutaminase-c-a-direct-fluorescence-read-out-that-distinguishes-the-binding-of-allosteric-inhibitors-from-activators
#7
Clint A Stalnecker, Jon W Erickson, Richard A Cerione
The first step in glutamine catabolism is catalyzed by the mitochondrial enzyme glutaminase, with a specific isoform, glutaminase C (GAC), being highly expressed in cancer cells. GAC activation requires the formation of homo-tetramers, promoted by anionic allosteric activators such as inorganic phosphate. This leads to the proper orientation of a flexible loop proximal to the dimer-dimer interface that is essential for catalysis (i.e. the activation loop). A major class of allosteric inhibitors of GAC, with the prototype being BPTES (bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide), and the related molecule CB-839, binds to the activation loop and induces the formation of an inactive tetramer (2 inhibitors bound per active tetramer)...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28159919/evaluation-of-radiofluorinated-carboximidamides-as-potential-ido-targeted-pet-tracers-for-cancer-imaging
#8
Xuan Huang, Zhongjie Pan, Michael L Doligalski, Xia Xiao, Epifanio Ruiz, Mikalai M Budzevich, Haibin Tian
IDO1 is an enzyme catalyzing the initial and rate-limiting step in the catabolism of tryptophan along the kynurenine pathway. IDO1 expression could suppress immune responses by blocking T-lymphocyte proliferation locally, suggesting a role of IDO in the regulation of immune responses. The goal of this study was to evaluate the potential of radiofluorinated carboximidamides as selective PET radioligands for IDO1. Specific binding correlated with IDO1 expression as measured through in vitro, microPET experiments...
January 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28117398/tryptophan-2-3-dioxygenase-tdo-deficiency-is-associated-with-subclinical-neuroprotection-in-a-mouse-model-of-multiple-sclerosis
#9
Tobias V Lanz, Sarah K Williams, Aleksandar Stojic, Simeon Iwantscheff, Jana K Sonner, Carl Grabitz, Simon Becker, Laura-Inés Böhler, Soumya R Mohapatra, Felix Sahm, Günter Küblbeck, Toshikazu Nakamura, Hiroshi Funakoshi, Christiane A Opitz, Wolfgang Wick, Ricarda Diem, Michael Platten
The catabolism of tryptophan to immunosuppressive and neuroactive kynurenines is a key metabolic pathway regulating immune responses and neurotoxicity. The rate-limiting step is controlled by indoleamine-2,3-dioxygenase (IDO) and tryptophan-2,3-dioxygenase (TDO). IDO is expressed in antigen presenting cells during immune reactions, hepatic TDO regulates blood homeostasis of tryptophan and neuronal TDO influences neurogenesis. While the role of IDO has been described in multiple immunological settings, little is known about TDO's effects on the immune system...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077028/ferulic-acid-suppresses-expression-of-tryptophan-metabolic-key-enzyme-indoleamine-2-3-dioxygenase-via-nf%C3%AE%C2%BAb-and-p38-mapk-in-lipopolysaccharide-stimulated-microglial-cells
#10
Manami Koshiguchi, Hitoshi Komazaki, Shizuka Hirai, Yukari Egashira
Ferulic acid (FA) is a phenol compound found in plants that has anti-inflammatory properties. Indoleamine 2, 3-dioxygenase (IDO) is a tryptophan catabolic enzyme induced in immune cells, including glial cells, during inflammation. Enhanced IDO expression leads to reduced tryptophan levels and increased levels of toxic metabolites, including quinolinic acid. Therefore, inhibition of IDO expression may be effective in suppressing progression of neurodegenerative diseases. In this study, we examined the effect of FA in microglial cells on IDO expression levels and related inflammatory signal molecules...
January 12, 2017: Bioscience, Biotechnology, and Biochemistry
https://www.readbyqxmd.com/read/28041837/the-fate-of-technical-grade-chlordane-in-mice-fed-a-high-fat-diet-and-its-roles-as-a-candidate-obesogen
#11
Dezhen Wang, Xinru Wang, Ping Zhang, Yao Wang, Renke Zhang, Jin Yan, Zhiqiang Zhou, Wentao Zhu
Epidemiological studies indicate that exposure to persistent organic pollutants is positively associated with the prevalence of obesity. To delineate the potential role of technical-grade chlordane in obesity development, chlordane metabolism and chlordane-induced metabolic changes were investigated in mice fed high-fat diet (HFD) over a 6-week period. Gas chromatography-electron capture detector analysis showed that HFD induced more accumulation of technical chlordane in the liver, muscle and adipose tissue...
March 2017: Environmental Pollution
https://www.readbyqxmd.com/read/27914477/in-vitro-rescue-of-genital-strains-of-chlamydia-trachomatis-from-interferon-%C3%AE-and-tryptophan-depletion-with-indole-positive-but-not-indole-negative-prevotella-spp
#12
Noa Ziklo, Wilhelmina M Huston, Kuong Taing, Mohammad Katouli, Peter Timms
BACKGROUND: The natural course of sexually transmitted infections caused by Chlamydia trachomatis varies between individuals. In addition to parasite and host effects, the vaginal microbiota might play a key role in the outcome of C. trachomatis infections. Interferon-gamma (IFN-γ), known for its anti-chlamydial properties, activates the expression of indoleamine 2,3-dioxygenase (IDO1) in epithelial cells, an enzyme that catabolizes the amino acid L- tryptophan into N-formylkynurenine, depleting the host cell's pool of tryptophan...
December 3, 2016: BMC Microbiology
https://www.readbyqxmd.com/read/27891058/ido2-a-pathogenic-mediator-of-inflammatory-autoimmunity
#13
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
#14
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
#15
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
#16
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
#17
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)...
2017: Cerebrovascular Diseases
https://www.readbyqxmd.com/read/27861556/antioxidant-properties-of-kynurenines-density-functional-theory-calculations
#18
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
#19
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)...
January 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/27819068/the-kynurenine-tryptophan-ratio-and-glioblastoma-patients-treated-with-hsppc-96-vaccine
#20
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.)
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