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fumaric acid

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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/28216384/novel-homozygous-pck1-mutation-causing-cytosolic-phosphoenolpyruvate-carboxykinase-deficiency-presenting-as-childhood-hypoglycemia-an-abnormal-pattern-of-urine-metabolites-and-liver-dysfunction
#3
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/28214312/update-treatment-of-necrobiosis-lipoidica
#4
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
#5
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
#6
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/28208702/the-glutamate-dehydrogenase-pathway-and-its-roles-in-cell-and-tissue-biology-in-health-and-disease
#7
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/28202494/fumarate-hydratase-is-a-critical-metabolic-regulator-of-hematopoietic-stem-cell-functions
#8
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/28186684/effect-of-different-sustained-bone-morphogenetic-protein-2-release-kinetics-on-bone-formation-in-poly-propylene-fumarate-scaffolds
#9
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
https://www.readbyqxmd.com/read/28170232/contaminant-removal-from-source-waters-using-cathodic-electrochemical-membrane-filtration-mechanisms-and-implications
#10
Junjian Zheng, Jinxing Ma, Zhiwei Wang, Shaoping Xu, T David Waite, Zhichao Wu
Removal of recalcitrant anthropogenic contaminants from water calls for the development of cost-effective treatment technologies. In this work, a novel electrochemical membrane filtration (EMF) process using a conducting microfiltration membrane as the cathode has been developed and the degradation of sulphanilic acid (SA) examined. The electrochemical degradation of SA in flow-by mode followed pseudo-first-order kinetics with the degradation rate enhanced with increase in charging voltage. Hydrogen peroxide as well as oxidants such as HO• and Fe(IV)O2+ were generated electrochemically with HO• found to be the dominant oxidant responsible for SA degradation...
February 7, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28166201/downregulation-of-pck2-remodels-tricarboxylic-acid-cycle-in-tumor-repopulating-cells-of-melanoma
#11
S Luo, Y Li, R Ma, J Liu, P Xu, H Zhang, K Tang, J Ma, N Liu, Y Zhang, Y Sun, T Ji, X Liang, X Yin, Y Liu, W Tong, Y Niu, N Wang, X Wang, B Huang
For cancer cells to proliferate, a balance must be built between biomass-forming, glucose-metabolized intermediates and ATP production. How intrinsic glucose carbon flow regulates this balance remains unclear. Here we show that mitochondrial phosphoenolpyruvate carboxykinase (PCK2), the hub molecule linking tricarboxylic acid (TCA) cycle, glycolysis and gluconeogenesis by conversion of mitochondrial oxaloacetate (OAA) to phosphoenolpyruvate, regulates glucose carbon flow direction in stem-like cells that repopulate tumors (tumor-repopulating cells (TRCs))...
February 6, 2017: Oncogene
https://www.readbyqxmd.com/read/28137214/phytochemical-constituents-ches-and-urease-inhibition-antiproliferative-and-antioxidant-properties-of-elaeagnus-umbellata-thunb
#12
Tevfik Ozen, Semiha Yenigun, Muhammed Altun, Ibrahim Demirtas
Due to the common ethnopharmacological used or scientifically examined biochemical properties, Elaeagnaceae family, Elaeagnus umbellata Thunb. (autumn olive) was worth investigated. In this investigation, we revealed antioxidant, antiproliferative and enzyme inhibition activities of the water, methanol, ethanol, acetone, ethyl acetate and hexane extracts of E. umbellata as well as contents of their phenolic, flavonoid, anthocyanin, ascorbic acid, lycopene and b-carotene. The antioxidant activity was screened by phosphomolybdenum assay...
January 27, 2017: Combinatorial Chemistry & High Throughput Screening
https://www.readbyqxmd.com/read/28117365/allosteric-inhibition-of-phosphoenolpyruvate-carboxylases-is-determined-by-a-single-amino-acid-residue-in-cyanobacteria
#13
Masahiro Takeya, Masami Yokota Hirai, Takashi Osanai
Phosphoenolpyruvate carboxylase (PEPC) is an important enzyme for CO2 fixation and primary metabolism in photosynthetic organisms including cyanobacteria. The kinetics and allosteric regulation of PEPCs have been studied in many organisms, but the biochemical properties of PEPC in the unicellular, non-nitrogen-fixing cyanobacterium Synechocystis sp. PCC 6803 have not been clarified. In this study, biochemical analysis revealed that the optimum pH and temperature of Synechocystis 6803 PEPC proteins were 7.3 and 30 °C, respectively...
January 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28111098/carbon-sources-tune-antibiotic-susceptibility-in-pseudomonas-aeruginosa-via-tricarboxylic-acid-cycle-control
#14
Sylvain Meylan, Caroline B M Porter, Jason H Yang, Peter Belenky, Arnaud Gutierrez, Michael A Lobritz, Jihye Park, Sun H Kim, Samuel M Moskowitz, James J Collins
Metabolically dormant bacteria present a critical challenge to effective antimicrobial therapy because these bacteria are genetically susceptible to antibiotic treatment but phenotypically tolerant. Such tolerance has been attributed to impaired drug uptake, which can be reversed by metabolic stimulation. Here, we evaluate the effects of central carbon metabolite stimulations on aminoglycoside sensitivity in the pathogen Pseudomonas aeruginosa. We identify fumarate as a tobramycin potentiator that activates cellular respiration and generates a proton motive force by stimulating the tricarboxylic acid (TCA) cycle...
January 16, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28107993/using-multiple-process-analytical-technology-probes-to-monitor-multivitamin-blends-in-a-tableting-feed-frame
#15
Pedro Durão, Clémence Fauteux-Lefebvre, Jean-Maxime Guay, Nicolas Abatzoglou, Ryan Gosselin
As Process Analytical Technology (PAT) implementation grows in the pharmaceutical industry, more studies are being performed to evaluate its suitability in new applications and processes within the manufacturing chain. As the last step in tablet production, the compression stage represents a critical phase that ensures product quality. In-line control put in place at this stage has the potential to detect powder blends that are out of specification limits and, thus, help to improve product quality. The objectives of the present project are to quantify the composition of a commercial 31-component multivitamin powder blend in real time on an industrial feed frame, using 3 different PAT tools: light-induced fluorescence spectroscopy, near infrared spectroscopy and red, green and blue color imaging...
March 1, 2017: Talanta
https://www.readbyqxmd.com/read/28106735/mass-spectrometry-based-metabolomic-and-lipidomic-analyses-of-the-effects-of-dietary-platycodon-grandiflorum-on-liver-and-serum-of-obese-mice-under-a-high-fat-diet
#16
Hye Min Park, Kab-Tae Park, Edmond Changkyun Park, Seung Ii Kim, Myung Sook Choi, Kwang-Hyeon Liu, Choong Hwan Lee
We aimed to identify metabolites involved in the anti-obesity effects of Platycodon grandiflorum (PG) in high-fat diet (HFD)-fed mice using mass spectrometry (MS)-based metabolomic techniques. C57BL/6J mice were divided into four groups: normal diet (ND)-fed mice, HFD-fed mice, HFD with 1% PG extract-fed mice (HPGL), and HFD with 5% PG extract-fed mice (HPGH). After 8 weeks, the HFD group gained more weight than the ND group, while dietary 5% PG extract attenuated this change. The partial least squares discriminant analysis (PLS-DA) score plots showed a clear distinction between experimental groups in serum and liver markers...
January 17, 2017: Nutrients
https://www.readbyqxmd.com/read/28098457/surface-forces-and-rheology-of-titanium-dioxide-in-the-presence-of-dicarboxylic-acids-from-molecular-interactions-to-yield-stress
#17
E-Jen Teh, Yee-Kwong Leong, Vincent S J Craig
The surface forces and yield stress of titanium dioxide were measured in the presence of dicarboxylic acids in order to understand the molecular basis for the observed rheological response. The yield stress was measured using the static vane technique, and the surface forces were characterized using an atomic force microscope. The trans and cis isomers of butenedioic acid (fumaric and maleic acids, respectively) were chosen as the relative orientation of the carboxylic groups differs substantially. This enables us to test the hypothesis that an increase in adhesion leads to an increase in yield stress as a consequence of the dicarboxylic acids participating in highly directed bridging...
January 31, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/28092423/-1-h-qnmr-quantification-of-annonaceous-acetogenins-in-crude-extracts-of-annona-muricata-l-fruit-pulp
#18
Natacha Bonneau, Timothé Cynober, Jean-Christophe Jullian, Pierre Champy
INTRODUCTION: Annonaceous acetogenins (AAGs) constitute a group of environmental neurotoxins, possibly implicated in sporadic atypical Parkinsonism/dementia complexes. The recent evidencing of complex mixtures of AAGs in edible fruits and derived food products requires efficient and practical analytical tools for an estimation of human exposure. OBJECTIVE: To develop a simple method for the direct quantitation of the majority of AAGs (sub-types 1a and 1b) within crude extracts, using commonly available (1) H-NMR spectrometers, for food control...
January 16, 2017: Phytochemical Analysis: PCA
https://www.readbyqxmd.com/read/28092212/systemic-medications-used-in-treatment-of-common-dermatological-conditions-safety-profile-with-respect-to-pregnancy-breast-feeding-and-content-in-seminal-fluid
#19
S M Brown, K A Aljefri, R Waas, P J Hampton
: Prescribing for pregnant or lactating patients and male patients wishing to father children can be a difficult area for dermatologists. There is a lack of review articles of commonly used systemic medications in dermatology with respect to their effects on developing embryogenesis and their potential transfer across the placenta, in breast milk and in seminal fluid. This paper aims to provide an up to date summary of evidence to better equip dermatologists to inform patients about the effects of systemic medications commonly used in dermatology to treat conditions such as atopic dermatitis, psoriasis and acne, on current and future embryogenesis and fertility...
January 16, 2017: Journal of Dermatological Treatment
https://www.readbyqxmd.com/read/28079150/sustained-kidney-biochemical-derangement-in-treated-experimental-diabetes-a-clue-to-metabolic-memory
#20
Antonio Anax F de Oliveira, Tiago F de Oliveira, Larissa L Bobadilla, Camila C M Garcia, Carolina Maria Berra, Nadja C de Souza-Pinto, Marisa H G Medeiros, Paolo Di Mascio, Roberto Zatz, Ana Paula de M Loureiro
The occurrence of biochemical alterations that last for a long period of time in diabetic individuals even after adequate handling of glycemia is an intriguing phenomenon named metabolic memory. In this study, we show that a kidney pathway is gradually altered during the course of diabetes and remains persistently changed after late glycemic control in streptozotocin-induced diabetic rats. This pathway comprises an early decline of uric acid clearance and pAMPK expression followed by fumarate accumulation, increased TGF-β expression, reduced PGC-1α expression, and downregulation of methylation and hydroxymethylation of mitochondrial DNA...
January 12, 2017: Scientific Reports
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