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https://www.readbyqxmd.com/read/28469468/kynurenine-pathway-of-tryptophan-metabolism-regulatory-and-functional-aspects
#1
REVIEW
Abdulla A-B Badawy
Regulatory and functional aspects of the kynurenine (K) pathway (KP) of tryptophan (Trp) degradation are reviewed. The KP accounts for ~95% of dietary Trp degradation, of which 90% is attributed to the hepatic KP. During immune activation, the minor extrahepatic KP plays a more active role. The KP is rate-limited by its first enzyme, Trp 2,3-dioxygenase (TDO), in liver and indoleamine 2,3-dioxygenase (IDO) elsewhere. TDO is regulated by glucocorticoid induction, substrate activation and stabilization by Trp, cofactor activation by heme, and end-product inhibition by reduced nicotinamide adenine dinucleotide (phosphate)...
2017: International Journal of Tryptophan Research: IJTR
https://www.readbyqxmd.com/read/28465467/indoleamine-2-3-dioxygenase-1-deficiency-attenuates-ccl4-induced-fibrosis-through-th17-cells-down-regulation-and-tryptophan-2-3-dioxygenase-compensation
#2
Weichao Zhong, Lei Gao, Zhenting Zhou, Haiyan Lin, Chun Chen, Peng Huang, Weiliang Huang, Chuying Zhou, Shaohui Huang, Linghui Nie, Ye Liu, Youming Chen, Daqiao Zhou, Zhiping Lv
Indoleamine 2,3-dioxygenase 1 (IDO1) is an intracellular rate-limiting enzyme in the metabolism of tryptophan along the kynurenine pathway, subsequently mediating the immune response; however, the role of IDO1 in liver fibrosis and cirrhosis is still unclear. In this study, we investigated the role of IDO1 in the development of hepatic fibrosis and cirrhosis. Patients with hepatitis B virus-induced cirrhosis and healthy volunteers were enrolled. For animals, carbon tetrachloride (CCl4) was used to establish liver fibrosis in wild-type and IDO1 knockout mice...
April 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28459584/role-of-the-dark-2ag-state-in-donor-acceptor-copolymers-as-a-pathway-for-singlet-fission-a-dmrg-study
#3
Jiajun Ren, Qian Peng, Xu Zhang, Yuanping Yi, Zhigang Shuai
The mechanism of intramolecular singlet fission in donor-acceptor-type copolymers, especially the role of the dark 2Ag state, is not so clear. In this Letter, the electronic structure of the benzodithiophene (B)-thiophene-1,1-dioxide (TDO) copolymer is calculated by density matrix renormalization group theory with the Pariser-Parr-Pople model. We find that the dark 2Ag state is the lowest singlet excited state and is nearly degenerate with the 1Bu state. So, a fast internal conversion from 1Bu to 2Ag state is highly possible...
May 3, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28454699/altered-placental-tryptophan-metabolic-pathway-in-human-fetal-growth-restriction
#4
Padma Murthi, Euan M Wallace, David W Walker
INTRODUCTION: Tryptophan is a substrate for kynurenine pathway metabolism in the placenta. We investigated if kynurenine metabolites change over gestation, if they are different between pregnancies with normal and fetal growth restriction (FGR), and if the oxygen environment modulated kynurenine pathway activity in the human placenta. METHODS: Tryptophan, kynurenine, and downstream kynurenine metabolites were determined in maternal venous blood, umbilical cord blood, and placental samples obtained in 1st and 3rd trimester pregnancies including FGR, and in the media of placental explants incubated with 20% or 5-8% O2 for 24, 48 or 72 h...
April 2017: Placenta
https://www.readbyqxmd.com/read/28410886/the-autogenous-graft-versus-transport-distraction-osteogenesis-for-reconstruction-of-the-ramus-condyle-unit-a-prospective-comparative-study
#5
S Kohli, S Mohanty, S Singh, Sandeep, J Dabas, R Patel
This study aimed to compare the joint function and morphology achieved following condylar reconstruction using sternoclavicular grafts (SCG) versus transport distraction osteogenesis (TDO) in temporomandibular joint (TMJ) ankylosis patients. Twenty-two patients with TMJ ankylosis underwent TMJ reconstruction with SCG or TDO (n=11 each). Radiographic and clinical evaluations were performed at 1 week and at 1, 3, and 6 months post-surgery. Clinical criteria examined included the duration of surgery, mean postoperative mouth opening, excursive jaw movements, and pain scores...
April 11, 2017: International Journal of Oral and Maxillofacial Surgery
https://www.readbyqxmd.com/read/28405495/biological-and-clinical-significance-of-tryptophan-catabolizing-enzymes-in-cutaneous-t-cell-lymphomas
#6
Pilvi Maliniemi, Kirsi Laukkanen, Liisa Väkevä, Katja Dettmer, Tuomas Lipsanen, Leila Jeskanen, Alban Bessede, Peter J Oefner, Marshall E Kadin, Annamari Ranki
Indoleamine 2,3-deoxygenase 1 (IDO1) induces immune tolerance in the tumor microenvironment (TME) and is recognized as a potential therapeutic target. We studied the expression of both IDO1 and the related tryptophan 2,3-dioxygenase (TDO) in several different subtypes of cutaneous T-cell lymphoma (CTCL), and evaluated the kynurenine (KYN) pathway in the local TME and in patient sera. Specimens from the total of 90 CTCL patients, including mycosis fungoides (MF, n = 37), lymphomatoid papulosis (LyP, n = 36), primary cutaneous anaplastic large cell lymphoma (pcALCL, n = 4), subcutaneous panniculitis-like T-cell lymphoma (SPTCL n = 13), and 10 patients with inflammatory lichen ruber planus (LRP), were analyzed by immunohistochemistry (IHC), immunofluorescence (IF), quantitative PCR, and/or liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28357780/targeting-tdo-in-cancer-immunotherapy
#7
REVIEW
Cheng-Peng Yu, Yun-Lei Song, Zheng-Ming Zhu, Bo Huang, Ying-Qun Xiao, Da-Ya Luo
Tryptophan-2,3-dioxygenase (TDO) is a homotetrameric heme-containing protein catalyzing the initial step in the kynurenine pathway, which oxidates the 2,3-double bond of the indole ring in L-tryptophan and catalyzes it into kynurenine (KYN). The upregulation of TDO results in a decrease in tryptophan and the accumulation of KYN and its metabolites. These metabolites can affect the proliferation of T cells. Increasing evidence demonstrates that TDO is a promising therapeutic target in the anti-tumor process...
May 2017: Medical Oncology
https://www.readbyqxmd.com/read/28338317/kinetics-and-mechanism-of-the-oxidation-of-thiourea-dioxide-by-iodine-in-a-slightly-acidic-medium
#8
Li Xu, László Valkai, Alena A Kuznetsova, Sergei V Makarov, Attila K Horváth
The thiourea dioxide (TDO)-iodine reaction was investigated spectrophotometrically monitoring the consumption of total amount of iodine at 468 nm, at T = 25.0 ± 0.1 °C, and at 0.5 M ionic strength in buffered slightly acidic medium. The nitrogen- and carbon-containing products were found to be ammonium ion and dissolved carbon dioxide, respectively, while from sulfur part sulfate ion was exclusively detected, when fresh TDO solution was used. The stoichiometry of the reaction was established as 2I2 + TDO + 4H2O → SO4(2-) + 2NH4(+) + 4I(-) + CO2 + 4H(+) indicating a strict 2:1 stoichiometric ratio...
March 24, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28314892/abnormal-kynurenine-pathway-of-tryptophan-catabolism-in-cardiovascular-diseases
#9
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/28298997/tricho-dento-osseous-syndrome-and-precocious-eruption
#10
Parul Jain, Rahul Kaul, Subrata Saha, Subir Sarkar
Tricho-dento-osseous syndrome (TDO), an uncommon form of ectodermal dysplasia is an autosomal dominant genetic disorder which is characterized by inherited defects in tissues arising from epithelial-mesenchymal interaction. Genetic studies have revealed that it is caused by mutation in the DLX3 gene. TDO presents with a great phenotypic heterogeneity and studies have suggested that this heterogeneity is the result of environmental factors or other genetic modifiers. In this article, we report a case of TDO in which the child had typical clinical features of hair, teeth and bone defects, as seen in TDO...
March 2017: Journal of Clinical and Experimental Dentistry
https://www.readbyqxmd.com/read/28214871/restraint-stress-during-pregnancy-rapidly-raises-kynurenic-acid-levels-in-mouse-placenta-and-fetal-brain
#11
Francesca M Notarangelo, Robert Schwarcz
Stressful events during pregnancy adversely affect brain development and may increase the risk of psychiatric disorders later in life. Early changes in the kynurenine (KYN) pathway (KP) of tryptophan (TRP) degradation, which contains several neuroactive metabolites, including kynurenic acid (KYNA), 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN), may constitute a molecular link between prenatal stress and delayed pathological consequences. To begin testing this hypothesis experimentally, we examined the effects of a 2-h restraint stress on KP metabolism in pregnant FVB/N mice on gestational day 17...
February 18, 2017: Developmental Neuroscience
https://www.readbyqxmd.com/read/28135572/dlx3-mutation-negatively-regulates-odontogenic-differentiation-of-human-dental-pulp-cells
#12
Li Zeng, Na Zhao, Dong Han, Haochen Liu, Yang Liu, Yixiang Wang, Hailan Feng
OBJECTIVES: The purpose of this study was to investigate the role of a novel mutant DLX3 on the odontogenic differentiation of human dental pulp cells (hDPCs) in tricho-dento-osseous (TDO) syndrome. DESIGN: hDPCs were obtained from the healthy premolars, stably-expressing wild-type DLX3 (WT), novel mutant DLX3 (Mu) and control vector (NC) cells were generated using recombinant lentiviruses. The proliferation rates of WT-hDPCs and Mu-hDPCs were measured by CCK8 assay...
May 2017: Archives of Oral Biology
https://www.readbyqxmd.com/read/28130499/amino-acid-catabolism-in-multiple-sclerosis-affects-immune-homeostasis
#13
Laura Negrotto, Jorge Correale
Amino acid catabolism has been implicated in immunoregulatory mechanisms present in several diseases, including autoimmune disorders. Our aims were to assess expression and activity of enzymes involved in Trp and Arg catabolism, as well as to investigate amino acid catabolism effects on the immune system of multiple sclerosis (MS) patients. To this end, 40 MS patients, 30 healthy control subjects, and 30 patients with other inflammatory neurological diseases were studied. Expression and activity of enzymes involved in Trp and Arg catabolism (IDO1, IDO2, Trp 2,3-dioxygenase [TDO], arginase [ARG] 1, ARG2, inducible NO synthetase) were evaluated in PBMCs...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28117398/tryptophan-2-3-dioxygenase-tdo-deficiency-is-associated-with-subclinical-neuroprotection-in-a-mouse-model-of-multiple-sclerosis
#14
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/28105265/targeting-the-inhibition-of-tryptophan-2-3-dioxygenase-tdo-2-for-cancer-treatment
#15
EDITORIAL
Ahmed F Abdel-Magid
No abstract text is available yet for this article.
January 12, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27995966/identification-of-an-evolutionary-conserved-structural-loop-that-is-required-for-the-enzymatic-and-biological-function-of-tryptophan-2-3-dioxygenase
#16
Helen Michels, Renée I Seinstra, Joost C M Uitdehaag, Mandy Koopman, Martijn van Faassen, Céline N Martineau, Ido P Kema, Rogier Buijsman, Ellen A A Nollen
The enzyme TDO (tryptophan 2,3-dioxygenase; TDO-2 in Caenorhabditis elegans) is a potential therapeutic target to cancer but is also thought to regulate proteotoxic events seen in the progression of neurodegenerative diseases. To better understand its function and develop specific compounds that target TDO we need to understand the structure of this molecule. In C. elegans we compared multiple different CRISPR/Cas9-induced tdo-2 deletion mutants and identified a motif of three amino acids (PLD) that is required for the enzymatic conversion of tryptophan to N-formylkynurenine...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27994758/fused-heterocyclic-compounds-as-potent-indoleamine-2-3-dioxygenase-1-inhibitors
#17
Subhankar Panda, Ashalata Roy, Suman Jyoti Deka, Vishal Trivedi, Debasis Manna
Uncontrolled metabolism of l-tryptophan (l-Trp) in the immune system has been recognized as a critical cellular process in immune tolerance. Indoleamine 2,3-dioxygenase 1 (IDO1) enzyme plays an important role in the metabolism of a local l-Trp through the kynurenine pathway in the immune systems. In this regard, IDO1 has emerged as a therapeutic target for the treatment of diseases that are associated with immune suppression like chronic infections, cancer, and others. In this study, we synthesized a series of pyridopyrimidine, pyrazolopyranopyrimidine, and dipyrazolopyran derivatives...
December 8, 2016: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27990653/population-pharmacokinetic-and-pharmacodynamic-modeling-of-epacadostat-in-patients-with-advanced-solid-malignancies
#18
Jack G Shi, Kevin J Bowman, Xuejun Chen, Janet Maleski, Lance Leopold, Swamy Yeleswaram
Epacadostat (EPA, INCB024360) is a selective inhibitor of the enzyme indoleamine 2,3-dioxygenase 1 (IDO1) and is being developed as an orally active immunotherapy to treat advanced malignancies. In the first clinical study investigating the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of EPA in oncology patients, increasing doses of EPA ranging from 50 mg once daily to 700 mg twice daily were administered as a monotherapy to 52 subjects with advanced solid tumors. The EPA plasma concentration-time profiles were adequately described by a population PK model comprised of the first-order kinetics of oral absorption with 2-compartment distribution and constant clearance from the central compartment...
December 19, 2016: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/27951658/analysis-of-reaction-intermediates-in-tryptophan-2-3-dioxygenase-a-comparison-with-indoleamine-2-3-dioxygenase
#19
COMPARATIVE STUDY
Jaswir Basran, Elizabeth S Booth, Michael Lee, Sandeep Handa, Emma L Raven
Indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are heme-containing enzymes that catalyze the O2-dependent oxidation of l-tryptophan (l-Trp) in biological systems. Although many decades have passed since their discovery, the mechanism of tryptophan oxidation has not been established. It has been widely assumed that IDO and TDO react using the same mechanism, although there is no evidence that they do. For IDO, a Compound II (ferryl) species accumulates in the steady state and is implicated in the mechanism; in TDO, no such species has ever been observed...
December 13, 2016: Biochemistry
https://www.readbyqxmd.com/read/27924851/senescence-novel-insight-into-dlx3-mutations-leading-to-enhanced-bone-formation-in-tricho-dento-osseous-syndrome
#20
Na Zhao, Dong Han, Haochen Liu, Yue Li, Sing-Wai Wong, Zhengyi Cao, Jian Xu, Xiaowei Zhang, Tao Cai, Yixiang Wang, Hailan Feng
The homeodomain transcription factor distal-less homeobox 3 gene (DLX3) is required for hair, tooth and skeletal development. DLX3 mutations have been found to be responsible for Tricho-Dento-Osseous (TDO) syndrome, characterized by kinky hair, thin-pitted enamel and increased bone density. Here we show that the DLX3 mutation (c.533 A>G; Q178R) attenuates osteogenic potential and senescence of bone mesenchymal stem cells (BMSCs) isolated from a TDO patient, providing a molecular explanation for abnormal increased bone density...
December 7, 2016: Scientific Reports
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