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Fumarate

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https://www.readbyqxmd.com/read/28219702/genetic-alterations-in-krebs-cycle-and-its-impact-on-cancer-pathogenesis
#1
REVIEW
Karishma Sajnani, Farhadul Islam, Robert Anthony Smith, Vinod Gopalan, Alfred King-Yin Lam
Cancer cells exhibit alterations in many cellular processes, including oxygen sensing and energy metabolism. Glycolysis in non-oxygen condition is the main energy production process in cancer rather than mitochondrial respiration as in benign cells. Genetic and epigenetic alterations of Krebs cycle enzymes favour the shift of cancer cells from oxidative phosphorylation to anaerobic glycolysis. Mutations in genes encoding aconitase, isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase, and citrate synthase are noted in many cancers...
February 17, 2017: Biochimie
https://www.readbyqxmd.com/read/28219662/fumarase-deficiency-causes-protein-and-metabolite-succination-and-intoxicates-mycobacterium-tuberculosis
#2
Nadine Ruecker, Robert Jansen, Carolina Trujillo, Susan Puckett, Pradeepa Jayachandran, Gerardo G Piroli, Norma Frizzell, Henrik Molina, Kyu Y Rhee, Sabine Ehrt
Enzymes of central carbon metabolism are essential mediators of Mycobacterium tuberculosis (Mtb) physiology and pathogenicity, but are often perceived to lack sufficient species selectivity to be pursued as potential drug targets. Fumarase (Fum) is an enzyme of the canonical tricarboxylic acid cycle and is dispensable in many organisms. Transposon mutagenesis studies in Mtb, however, indicate that Fum is required for optimal growth. Here, we report the generation and characterization of a genetically engineered Mtb strain in which Fum expression is conditionally regulated...
February 9, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28218056/regulation-of-the-escherichia-coli-ydhy-t-operon-in-the-presence-of-alternative-electron-acceptors
#3
Naji Al Ibrahim, Jeffrey Green
The Escherichia coli K-12 ydhY-T operon, coding for a predicted oxidoreductase complex, is activated under anaerobic conditions and repressed in the presence of nitrate or nitrite. Anaerobic activation is mediated by the transcription factor FNR and nitrate/nitrite repression is mediated by NarXL and NarQP. In vitro transcription reactions revealed that the DNA upstream of ydhY-T contains sufficient information for RNA polymerase alone to initiate transcription from five locations. FNR severely inhibited synthesis of two of these transcripts (located upstream of, and within, the FNR binding site) and activated the FNR-dependent promoter previously identified in vivo...
February 3, 2017: Microbiology
https://www.readbyqxmd.com/read/28217362/crystal-structure-of-dimethyl-2-2z-5z-5-2-meth-oxy-2-oxo-ethyl-idene-2-e-2-methyl-5-prop-1-en-2-yl-cyclo-hex-2-enyl-idene-hydrazinyl-idene-4-oxo-thia-zolidin-3-yl-fumarate
#4
Abdellah N'ait Ousidi, My Youssef Ait Itto, Aziz Auhmani, Abdelkhalek Riahi, Abdelwahed Auhmani, Jean-Claude Daran
The crystal structure and the conformation of the title compound, C22H27N3O7S, were determined from the synthetic pathway and by X-ray analysis. This compound is a new 4-thia-zolidinone derivative prepared and isolated as pure product from thio-semicarbazone carvone. The mol-ecule is built up from an oxo-thia-zolidine ring tetra-substituted by a meth-oxy-oxo-ethyl-idene, a maleate, an oxygen and a cyclo-hexyl-idene-hydrazone. The cyclo-hexyl-idene ring is statistically disordered over two positions, resulting in an inversion of configuration for the substituted carbon...
February 1, 2017: Acta Crystallographica. Section E, Crystallographic Communications
https://www.readbyqxmd.com/read/28216384/novel-homozygous-pck1-mutation-causing-cytosolic-phosphoenolpyruvate-carboxykinase-deficiency-presenting-as-childhood-hypoglycemia-an-abnormal-pattern-of-urine-metabolites-and-liver-dysfunction
#5
Päivi Vieira, Jessie Cameron, Elisa Rahikkala, Riikka Keski-Filppula, Lin-Hua Zhang, Saikat Santra, Allison Matthews, Päivi Myllynen, Matti Nuutinen, Jukka S Moilanen, Richard J Rodenburg, Arndt Rolfs, Johanna Uusimaa, Clara D M van Karnebeek
Clinical and laboratory data were collected from three Finnish patients including a sibling pair and another unrelated child with unexplained childhood hypoglycemia. Transient elevation of alanine transaminase, lactate and tricarboxylic acid cycle intermediates, especially fumarate, were noticed in urine organic acid analysis. Exome sequencing was performed for the patients and their parents. A novel homozygous PCK1 c.925G>A (p.G309R) mutation was detected in all affected individuals. COS-1 cells transfected with mutant PCK1 transcripts were used to study the pathogenic nature of the detected variant...
February 6, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28215615/factors-associated-with-persistent-increase-in-level-of-alanine-aminotransferase-in-patients-with-chronic-hepatitis-b-receiving-oral-antiviral-therapy
#6
Ira M Jacobson, Mary K Washington, Maria Buti, Alexander Thompson, Nezam Afdhal, Robert Flisiak, Ulus Salih Akarca, Konstantin G Tchernev, John F Flaherty, Raul Aguilar Schall, Robert P Myers, G Mani Subramanian, John G McHutchison, Zobair Younossi, Patrick Marcellin, Keyur Patel
BACKGROUND & AIM: Despite complete suppression of viral DNA with antiviral agents, in some patients with chronic hepatitis B (CHB), serum levels of alanine aminotransferase (ALT) do not normalize. We investigated factors associated with persistent increases in level of ALT in patients with CHB given long-term tenofovir disoproxil fumarate. METHODS: We analyzed data from 471 hepatitis B e antigen (HBeAg)-positive and HBeAg-negative patients with CHB participating in 2 phase 3 trials...
February 12, 2017: Clinical Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28214969/attached-and-suspended-denitrifier-communities-in-pristine-limestone-aquifers-harbor-high-fractions-of-potential-autotrophs-oxidizing-reduced-iron-and-sulfur-compounds
#7
M Herrmann, S Opitz, R Harzer, K U Totsche, K Küsel
Oxygen and nitrate availability as well as the presence of suitable organic or inorganic electron donors are strong drivers of denitrification; however, the factors influencing denitrifier abundance and community composition in pristine aquifers are not well understood. We explored the denitrifier community structure of suspended and attached groundwater microorganisms in two superimposed limestone aquifer assemblages with contrasting oxygen regime in the Hainich Critical Zone Exploratory (Germany). Attached communities were retrieved from freshly crushed parent rock material which had been exposed for colonization in two groundwater wells (12...
February 18, 2017: Microbial Ecology
https://www.readbyqxmd.com/read/28214312/update-treatment-of-necrobiosis-lipoidica
#8
REVIEW
Melanie Peckruhn, Jörg Tittelbach, Peter Elsner
Necrobiosis lipoidica (NL) is a rare granulomatous disease of hitherto unclear etiology frequently seen in patients with diabetes. Characterized by its potential for ulcerations, it often presents a serious burden for those affected. There are currently neither German nor European guidelines for the treatment of NL. At the same time, standard treatment with topical or intralesional corticosteroids does not always show satisfactory results. We therefore set out to evaluate whether the various treatment regimens published since 2000 have actually expanded the therapeutic armamentarium in a relevant manner...
February 2017: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/28214304/efficacy-and-safety-of-fumaric-acid-esters-in-combination-with-phototherapy-in-patients-with-moderate-to-severe-plaque-psoriasis-fast
#9
Peter Weisenseel, Kristian Reich, Wiebke Griemberg, Katharina Merten, Christine Gröschel, Natalie Nunez Gomez, Kirsi Taipale, Beate Bräu, Ina Zschocke
BACKGROUND: While treatment of patients with moderate-to-severe psoriasis using a combination of fumaric acid esters (FAE, Fumaderm(®) ) and phototherapy (UV) is common practice, there have been hardly any studies investigating this regimen. Available information is limited to data from a small pilot study. The objective of the present study was to evaluate FAE/UV combination therapy in a larger patient cohort with moderate-to-severe psoriasis. PATIENTS AND METHODS: In this prospective noninterventional multicenter study, data from patients treated with FAE/UV combination therapy was assessed with regard to efficacy (PGA' PASI, DLQI, EQ-5D), safety, and dosage over a twelve-month period...
February 2017: Journal der Deutschen Dermatologischen Gesellschaft, Journal of the German Society of Dermatology: JDDG
https://www.readbyqxmd.com/read/28213313/structural-investigation-of-the-cocrystal-formed-between-5-fluorocytosine-and-fumaric-acid-based-on-vibrational-spectroscopic-technique
#10
Yong Du, Qiang Cai, Jiadan Xue, Qi Zhang, Dan Qin
The vibrational spectra of 5-fluorocytosine, fumaric acid and their cocrystal were measured using terahertz time-domain spectroscopy (THz-TDS) and Raman spectroscopy at room temperature. Experimental THz results show that the cocrystal has distinct fingerprint spectra in terahertz region. The absorption peaks observed in the terahertz spectra of the cocrystal were at 0.61 and 0.91THz. These are quite different from corresponding raw starting materials. Raman spectra also show similar results about differences between the cocrystal and corresponding raw starting materials...
February 7, 2017: Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy
https://www.readbyqxmd.com/read/28212755/stimulating-central-carbon-metabolism-to-re-sensitize-pseudomonas-aeruginosa-to-aminoglycosides
#11
Dorival Martins, Dao Nguyen
In this issue of Cell Chemical Biology, Meylan et al. (2017) examine how stimulation of central carbon metabolism of Pseudomonas aeruginosa modulates aminoglycoside lethality in tolerant bacteria. They identify fumarate as a tobramycin potentiator that stimulates proton motive force-dependent drug uptake and increases respiration-dependent killing.
February 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28211024/comparative-effectiveness-research-of-disease-modifying-therapies-for-the-management-of-multiple-sclerosis-analysis-of-a-large-health-insurance-claims-database
#12
Aaron Boster, Jacqueline Nicholas, Ning Wu, Wei-Shi Yeh, Monica Fay, Michael Edwards, Ming-Yi Huang, Andrew Lee
INTRODUCTION: Limited data are available on the real-world effectiveness of newer oral disease-modifying therapies (DMTs) in multiple sclerosis. The purpose of this study was to retrospectively compare the real-world effectiveness of dimethyl fumarate (DMF), fingolimod, teriflunomide, and injectable DMTs in routine clinical practice based on US claims data. METHODS: Patients newly-initiating DMF, interferon beta (IFNβ), glatiramer acetate (GA), teriflunomide, or fingolimod in 2013 were identified in the Truven MarketScan Commercial Claims Databases (N = 6372)...
February 16, 2017: Neurology and Therapy
https://www.readbyqxmd.com/read/28209921/dimethyl-fumarate-for-ischemic-stroke
#13
EDITORIAL
Reiner Kunze
No abstract text is available yet for this article.
February 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28209373/cost-utility-of-first-line-disease-modifying-treatments-for-relapsing-remitting-multiple-sclerosis
#14
Erkki Soini, Jaana Joutseno, Marja-Liisa Sumelahti
PURPOSE: This study evaluated the cost-effectiveness of first-line treatments of relapsing-remitting multiple sclerosis (RRMS) (dimethyl fumarate [DMF] 240 mg PO BID, teriflunomide 14 mg once daily, glatiramer acetate 20 mg SC once daily, interferon [IFN]-β1a 44 µg TIW, IFN-β1b 250 µg EOD, and IFN-β1a 30 µg IM QW) and best supportive care (BSC) in the health care payer setting in Finland. METHODS: The primary outcome was the modeled incremental cost-effectiveness ratio (ICER; €/quality-adjusted life-year [QALY] gained, 3%/y discounting)...
February 13, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28208702/the-glutamate-dehydrogenase-pathway-and-its-roles-in-cell-and-tissue-biology-in-health-and-disease
#15
REVIEW
Andreas Plaitakis, Ester Kalef-Ezra, Dimitra Kotzamani, Ioannis Zaganas, Cleanthe Spanaki
Glutamate dehydrogenase (GDH) is a hexameric enzyme that catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonia while reducing NAD(P)⁺ to NAD(P)H. It is found in all living organisms serving both catabolic and anabolic reactions. In mammalian tissues, oxidative deamination of glutamate via GDH generates α-ketoglutarate, which is metabolized by the Krebs cycle, leading to the synthesis of ATP. In addition, the GDH pathway is linked to diverse cellular processes, including ammonia metabolism, acid-base equilibrium, redox homeostasis (via formation of fumarate), lipid biosynthesis (via oxidative generation of citrate), and lactate production...
February 8, 2017: Biology
https://www.readbyqxmd.com/read/28208119/hiv-prevention-opportunities-and-challenges
#16
Jeanne M Marrazzo
Preexposure prophylaxis (PrEP) with tenofovir disoproxil fumarate (TDF)-based regimens has been shown to be effective in preventing acquisition of HIV infection, with protective efficacy being dependent on adherence to treatment. Data from the PROUD (Preexposure Option for Reducing HIV in the UK) and IPERGAY (Action to Prevent Risk Exposure By and For Gay Men) studies, the later of which employed event-driven PrEP, showed a high rate of protective efficacy of PrEP with TDF and emtricitabine among men who have sex with men...
December 2017: Topics in Antiviral Medicine
https://www.readbyqxmd.com/read/28202494/fumarate-hydratase-is-a-critical-metabolic-regulator-of-hematopoietic-stem-cell-functions
#17
Amelie V Guitart, Theano I Panagopoulou, Arnaud Villacreces, Milica Vukovic, Catarina Sepulveda, Lewis Allen, Roderick N Carter, Louie N van de Lagemaat, Marcos Morgan, Peter Giles, Zuzanna Sas, Marta Vila Gonzalez, Hannah Lawson, Jasmin Paris, Joy Edwards-Hicks, Katrin Schaak, Chithra Subramani, Deniz Gezer, Alejandro Armesilla-Diaz, Jimi Wills, Aaron Easterbrook, David Coman, Chi Wai Eric So, Donal O'Carroll, Douglas Vernimmen, Neil P Rodrigues, Patrick J Pollard, Nicholas M Morton, Andrew Finch, Kamil R Kranc
Strict regulation of stem cell metabolism is essential for tissue functions and tumor suppression. In this study, we investigated the role of fumarate hydratase (Fh1), a key component of the mitochondrial tricarboxylic acid (TCA) cycle and cytosolic fumarate metabolism, in normal and leukemic hematopoiesis. Hematopoiesis-specific Fh1 deletion (resulting in endogenous fumarate accumulation and a genetic TCA cycle block reflected by decreased maximal mitochondrial respiration) caused lethal fetal liver hematopoietic defects and hematopoietic stem cell (HSC) failure...
February 15, 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28195560/impact-of-tenofovir-dose-adjustment-on-both-estimated-glomerular-filtration-rate-and-tenofovir-trough-concentration
#18
Sylvie Bregigeon, Caroline Solas, Olivia Faucher, Véronique Obry-Roguet, Catherine Tamalet, Isabelle Poizot-Martin
BACKGROUND: Tenofovir disoproxil fumarate (TDF)-based regimen is a treatment option for HIV-infected patients. TDF dose adjustment is recommended in patients with impaired renal function. We assessed the impact of TDF dose adjustment on renal function and tenofovir trough concentration. METHODS: Fourteen HIV patients for whom TDF dose was adjusted (1 tablet/48h) because of estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73m(2), and/or due to a tenofovir trough concentration > 90 ng/mL between 2006 and 2013 were selected...
February 14, 2017: Antiviral Therapy
https://www.readbyqxmd.com/read/28195105/hereditary-leiomyomatosis-and-renal-cell-cancer-syndrome-associated-renal-cell-carcinoma
#19
Shraddha Adamane, Sangeeta Desai, Santosh Menon
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is a recently described entity with unknown exact prevalence. The affected individuals are predisposed to have multiple leiomyomas and renal cancer due to germline mutation in fumarate hydratase gene on chromosome 1. The knowledge of this rare tumour is essential for early recognition and institution of appropriate therapy, since they have a grave prognosis. Herein, we present the first case from India of HLRCC in a 42 year old lady who presented with a renal mass and metastasis with consequent fulminant course of disease...
January 2017: Indian Journal of Pathology & Microbiology
https://www.readbyqxmd.com/read/28186684/effect-of-different-sustained-bone-morphogenetic-protein-2-release-kinetics-on-bone-formation-in-poly-propylene-fumarate-scaffolds
#20
Maurits G L Olthof, Diederik H R Kempen, James L Herrick, Michael J Yaszemski, Wouter J A Dhert, Lichun Lu
To investigate the effect of sustained bone morphogenetic protein-2 (BMP-2) release kinetics on bone formation in poly(propylene fumarate) (PPF) scaffolds, different poly(lactic-co-glycolic acid) (PLGA) microspheres were used as delivery vehicles. All PPF scaffolds had the same 75% porous structure, while the degradation rate of the embedded PLGA microspheres was changed to tailor BMP-2 release by varying the lactic-to-glycolic acid (L:G) ratio in the copolymer. Four PLGA microsphere formulations with 50/50, 65/35, 75/25, and 85/15 L:G ratios and varying in vivo degradation rates were fabricated...
February 10, 2017: Journal of Biomedical Materials Research. Part B, Applied Biomaterials
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