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https://www.readbyqxmd.com/read/28107627/use-of-tissue-metabolite-analysis-and-enzyme-kinetics-to-discriminate-between-alternate-pathways-for-hydrogen-sulfide-metabolism
#1
Kristie D Cox Augustyn, Michael R Jackson, Marilyn Schuman Jorns
Hydrogen sulfide (H2S) is an endogenously synthesized signaling molecule that is enzymatically metabolized in mitochondria. The metabolism of H2S maintains optimal concentrations of the gasotransmitter and produces sulfane sulfur (S(0))-containing metabolites that may be functionally important in signaling. Sulfide:quinone oxidoreductase (SQOR) catalyzes the initial 2-electron oxidation of H2S to S(0) using coenzyme Q as electron acceptor in a reaction that requires a third substrate to act as the acceptor of S(0)...
January 20, 2017: Biochemistry
https://www.readbyqxmd.com/read/28099869/amitriptyline-down-regulates-coenzyme-q10-biosynthesis-in-lung-cancer-cells
#2
Tamara Ortiz, Marina Villanueva-Paz, Eduardo Díaz-Parrado, Matilde Illanes, Ana Fernández-Rodríguez, José A Sánchez-Alcázar, Manuel de Miguel
Amitriptyline, a tricyclic antidepressant, has been proposed as an antitumoral drug in oxidative therapy. Its pro-apoptotic effects, mediated by high reactive oxygen species generation, have been already described. In this study we analysed the effect of amitriptyline on the biosynthesis of coenzyme Q10 (CoQ), an essential component for electron transport and a potent membrane antioxidant involved in redox signaling. We treated H460 cells, a non-small-cell lung cancer cell line, with amitriptyline and we analyzed CoQ levels by HPLC and CoQ biosynthesis rate, as well as the enzymes involved in CoQ biosynthesis by real-time PCR and Western blot...
January 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28064038/characterization-of-hexose-transporters-in-yarrowia-lipolytica-reveals-new-groups-of-sugar-porters-involved-in-yeast-growth
#3
Zbigniew Lazar, Cécile Neuvéglise, Tristan Rossignol, Hugo Devillers, Nicolas Morin, Małgorzata Robak, Jean-Marc Nicaud, Anne-Marie Crutz-Le Coq
Sugar assimilation has been intensively studied in the model yeast S. cerevisiae, and for two decades, it has been clear that the homologous HXT genes, which encode a set of hexose transporters, play a central role in this process. However, in the yeast Yarrowia lipolytica, which is well-known for its biotechnological applications, sugar assimilation is only poorly understood, even though this yeast exhibits peculiar intra-strain differences in fructose uptake: some strains (e.g., W29) are known to be slow-growing in fructose while others (e...
January 4, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/28001060/biosynthesis-of-antroquinonol-and-4-acetylantroquinonol-b-via-a-polyketide-pathway-using-orsellinic-acid-as-a-ring-precursor-in-antrodia-cinnamomea
#4
Kevin Chi-Chung Chou, Shang-Han Yang, Hsiang-Lin Wu, Pei-Yin Lin, Tsu-Liang Chang, Fuu Sheu, Kai-Hsien Chen, Been-Huang Chiang
Antroquinonol (AQ) and 4-acetylantroquinonol B (4-AAQB), isolated from the mycelium of Antrodia cinnamomea, have a similar chemical backbone to coenzyme Q (CoQ). Based on the postulation that biosynthesis of both AQ and 4-AAQB in A. cinnamomea starts from the polyketide pathway, we cultivated this fungus in a culture medium containing [U-(13)C]oleic acid, and then we analyzed the crude extracts of the mycelium using UHPLC-MS. We found that AQ and 4-AAQB follow similar biosynthetic sequences as CoQ. Obvious [(13)C2] fragments on the ring backbone were detected in the mass spectrum for [(13)C2]AQ, [(13)C2]4-AAQB, and their [(13)C2] intermediates found in this study...
December 21, 2016: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/27996031/mild-intrauterine-hypoperfusion-reproduces-neurodevelopmental-disorders-observed-in-prematurity
#5
Makiko Ohshima, Jacques-Olivier Coq, Kentaro Otani, Yorito Hattori, Yuko Ogawa, Yoshiaki Sato, Mariko Harada-Shiba, Masafumi Ihara, Masahiro Tsuji
Severe intrauterine ischemia is detrimental to the developing brain. The impact of mild intrauterine hypoperfusion on neurological development, however, is still unclear. We induced mild intrauterine hypoperfusion in rats on embryonic day 17 via arterial stenosis with metal microcoils wrapped around the uterine and ovarian arteries. All pups were born with significantly decreased birth weights. Decreased gray and white matter areas were observed without obvious tissue damage. Pups presented delayed newborn reflexes, muscle weakness, and altered spontaneous activity...
December 20, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27913695/a-randomized-double-blind-placebo-controlled-trial-of-coenzyme-q10-in-huntington-disease
#6
Andrew McGarry, Michael McDermott, Karl Kieburtz, Elisabeth A de Blieck, Flint Beal, Karen Marder, Christopher Ross, Ira Shoulson, Peter Gilbert, William M Mallonee, Mark Guttman, Joanne Wojcieszek, Rajeev Kumar, Mark S LeDoux, Mary Jenkins, H Diana Rosas, Martha Nance, Kevin Biglan, Peter Como, Richard M Dubinsky, Kathleen M Shannon, Padraig O'Suilleabhain, Kelvin Chou, Francis Walker, Wayne Martin, Vicki L Wheelock, Elizabeth McCusker, Joseph Jankovic, Carlos Singer, Juan Sanchez-Ramos, Burton Scott, Oksana Suchowersky, Stewart A Factor, Donald S Higgins, Eric Molho, Fredy Revilla, John N Caviness, Joseph H Friedman, Joel S Perlmutter, Andrew Feigin, Karen Anderson, Ramon Rodriguez, Nikolaus R McFarland, Russell L Margolis, Eric S Farbman, Lynn A Raymond, Valerie Suski, Sandra Kostyk, Amy Colcher, Lauren Seeberger, Eric Epping, Sherali Esmail, Nancy Diaz, Wai Lun Alan Fung, Alan Diamond, Samuel Frank, Philip Hanna, Neal Hermanowicz, Leon S Dure, Merit Cudkowicz
OBJECTIVE: To test the hypothesis that chronic treatment of early-stage Huntington disease (HD) with high-dose coenzyme Q10 (CoQ) will slow the progressive functional decline of HD. METHODS: We performed a multicenter randomized, double-blind, placebo-controlled trial. Patients with early-stage HD (n = 609) were enrolled at 48 sites in the United States, Canada, and Australia from 2008 to 2012. Patients were randomized to receive either CoQ 2,400 mg/d or matching placebo, then followed for 60 months...
January 10, 2017: Neurology
https://www.readbyqxmd.com/read/27856619/coq-deficiency-causes-disruption-of-mitochondrial-sulfide-oxidation-a-new-pathomechanism-associated-with-this-syndrome
#7
Marta Luna-Sánchez, Agustín Hidalgo-Gutiérrez, Tatjana M Hildebrandt, Julio Chaves-Serrano, Eliana Barriocanal-Casado, Ángela Santos-Fandila, Miguel Romero, Ramy Ka Sayed, Juan Duarte, Holger Prokisch, Markus Schuelke, Felix Distelmaier, Germaine Escames, Darío Acuña-Castroviejo, Luis C López
Coenzyme Q (CoQ) is a key component of the mitochondrial respiratory chain, but it also has several other functions in the cellular metabolism. One of them is to function as an electron carrier in the reaction catalyzed by sulfide:quinone oxidoreductase (SQR), which catalyzes the first reaction in the hydrogen sulfide oxidation pathway. Therefore, SQR may be affected by CoQ deficiency. Using human skin fibroblasts and two mouse models with primary CoQ deficiency, we demonstrate that severe CoQ deficiency causes a reduction in SQR levels and activity, which leads to an alteration of mitochondrial sulfide metabolism...
January 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27856618/coenzyme-q-deficiency-causes-impairment-of-the-sulfide-oxidation-pathway
#8
Marcello Ziosi, Ivano Di Meo, Giulio Kleiner, Xing-Huang Gao, Emanuele Barca, Maria J Sanchez-Quintero, Saba Tadesse, Hongfeng Jiang, Changhong Qiao, Richard J Rodenburg, Emmanuel Scalais, Markus Schuelke, Belinda Willard, Maria Hatzoglou, Valeria Tiranti, Catarina M Quinzii
Coenzyme Q (CoQ) is an electron acceptor for sulfide-quinone reductase (SQR), the first enzyme of the hydrogen sulfide oxidation pathway. Here, we show that lack of CoQ in human skin fibroblasts causes impairment of hydrogen sulfide oxidation, proportional to the residual levels of CoQ. Biochemical and molecular abnormalities are rescued by CoQ supplementation in vitro and recapitulated by pharmacological inhibition of CoQ biosynthesis in skin fibroblasts and ADCK3 depletion in HeLa cells. Kidneys of Pdss2(kd/kd) mice, which only have ~15% residual CoQ concentrations and are clinically affected, showed (i) reduced protein levels of SQR and downstream enzymes, (ii) accumulation of hydrogen sulfides, and (iii) glutathione depletion...
January 2017: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/27852445/a-metabolomics-driven-approach-reveals-metabolic-responses-and-mechanisms-in-the-rat-heart-following-myocardial-infarction
#9
Miso Nam, Youngae Jung, Do Hyun Ryu, Geum-Sook Hwang
BACKGROUND: Myocardial infarction (MI) is caused by myocardial necrosis resulting from prolonged ischemia. However, the biological mechanisms underlying MI remain unclear. METHODS: We evaluated metabolic and lipidomic changes in rat heart tissue from sham and MI at 1h, 1day and 10day after coronary ligation, using global profiling based on metabolomics. RESULTS: A time-dependent increase or decrease in polar and lipid metabolite levels was measured...
January 15, 2017: International Journal of Cardiology
https://www.readbyqxmd.com/read/27837315/cloning-and-characterization-of-decaprenyl-diphosphate-synthase-from-three-different-fungi
#10
Daisuke Moriyama, Tomohiro Kaino, Kazuyoshi Yajima, Ryota Yanai, Yasuhiro Ikenaka, Junzo Hasegawa, Motohisa Washida, Hirokazu Nanba, Makoto Kawamukai
Coenzyme Q (CoQ) is composed of a benzoquinone moiety and an isoprenoid side chain of varying lengths. The length of the side chain is controlled by polyprenyl diphosphate synthase. In this study, dps1 genes encoding decaprenyl diphosphate synthase were cloned from three fungi: Bulleromyces albus, Saitoella complicata, and Rhodotorula minuta. The predicted Dps1 proteins contained seven conserved domains found in typical polyprenyl diphosphate synthases and were 528, 440, and 537 amino acids in length in B. albus, S...
November 11, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27732833/hypothesis-driven-versus-hypothesis-free-filling-the-gaps-in-coq-biosynthesis
#11
José Antonio Enríquez, Fátima Sánchez-Cabo, Jesús Vázquez
Two independent investigations based on the power of yeast genetics, but using radically different discovery-driven approaches, have solved a long-pursued goal: the understanding of the early steps in CoQ biosynthesis, which may help diagnose CoQ deficiencies of unknown origin (Payet et al., 2016; Stefely et al., 2016).
October 11, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27669165/mitochondrial-protein-functions-elucidated-by-multi-omic-mass-spectrometry-profiling
#12
Jonathan A Stefely, Nicholas W Kwiecien, Elyse C Freiberger, Alicia L Richards, Adam Jochem, Matthew J P Rush, Arne Ulbrich, Kyle P Robinson, Paul D Hutchins, Mike T Veling, Xiao Guo, Zachary A Kemmerer, Kyle J Connors, Edna A Trujillo, Jacob Sokol, Harald Marx, Michael S Westphall, Alexander S Hebert, David J Pagliarini, Joshua J Coon
Mitochondrial dysfunction is associated with many human diseases, including cancer and neurodegeneration, that are often linked to proteins and pathways that are not well-characterized. To begin defining the functions of such poorly characterized proteins, we used mass spectrometry to map the proteomes, lipidomes, and metabolomes of 174 yeast strains, each lacking a single gene related to mitochondrial biology. 144 of these genes have human homologs, 60 of which are associated with disease and 39 of which are uncharacterized...
November 2016: Nature Biotechnology
https://www.readbyqxmd.com/read/27651221/deciphering-how-lip2-and-pox2-promoters-can-optimally-regulate-recombinant-protein-production-in-the-yeast-yarrowia-lipolytica
#13
Hosni Sassi, Frank Delvigne, Tambi Kar, Jean-Marc Nicaud, Anne-Marie Crutz-Le Coq, Sebastien Steels, Patrick Fickers
BACKGROUND: In recent years, the non-conventional model yeast species Yarrowia lipolytica has received much attention because it is a useful cell factory for producing recombinant proteins. In this species, expression vectors involving LIP2 and POX2 promoters have been developed and used successfully for protein production at yields similar to or even higher than those of other cell factories, such as Pichia pastoris. However, production processes involving these promoters can be difficult to manage, especially if carried out at large scales in fed-batch bioreactors, because they require hydrophobic inducers, such as oleic acid or methyl oleate...
September 20, 2016: Microbial Cell Factories
https://www.readbyqxmd.com/read/27564375/quantification-of-the-fungal-fraction-released-from-various-preloaded-fibrous-filters-during-a-simulated-ventilation-restart
#14
K Morisseau, A Joubert, L Le Coq, Y Andres
This study aimed to demonstrate that particles, especially those associated with fungi, could be released from fibrous filters used in the air-handling unit (AHU) of heating, ventilation and air-conditioning (HVAC) systems during ventilation restarts. Quantification of the water retention capacity and SEM pictures of the filters was used to show the potential for fungal proliferation in unused or preloaded filters. Five fibrous filters with various particle collection efficiencies were studied: classes G4, M5, M6, F7, and combined F7 according to European standard EN779:2012...
August 26, 2016: Indoor Air
https://www.readbyqxmd.com/read/27510225/dietary-and-microbiome-factors-determine-longevity-in-caenorhabditis-elegans
#15
Adolfo Sánchez-Blanco, Alberto Rodríguez-Matellán, Ana González-Paramás, Susana González-Manzano, Stuart K Kim, Faustino Mollinedo
Diet composition affects organismal health. Nutrient uptake depends on the microbiome. Caenorhabditis elegans fed a Bacillus subtilis diet live longer than those fed the standard Escherichia coli diet. Here we report that this longevity difference is primarily caused by dietary coQ, an antioxidant synthesized by E. coli but not by B. subtilis. CoQ-supplemented E. coli fed worms have a lower oxidation state yet live shorter than coQ-less B. subtilis fed worms. We showed that mutations affecting longevity for E...
July 2016: Aging
https://www.readbyqxmd.com/read/27503795/a-clock-network-for-geodesy-and-fundamental-science
#16
C Lisdat, G Grosche, N Quintin, C Shi, S M F Raupach, C Grebing, D Nicolodi, F Stefani, A Al-Masoudi, S Dörscher, S Häfner, J-L Robyr, N Chiodo, S Bilicki, E Bookjans, A Koczwara, S Koke, A Kuhl, F Wiotte, F Meynadier, E Camisard, M Abgrall, M Lours, T Legero, H Schnatz, U Sterr, H Denker, C Chardonnet, Y Le Coq, G Santarelli, A Amy-Klein, R Le Targat, J Lodewyck, O Lopez, P-E Pottie
Leveraging the unrivalled performance of optical clocks as key tools for geo-science, for astronomy and for fundamental physics beyond the standard model requires comparing the frequency of distant optical clocks faithfully. Here, we report on the comparison and agreement of two strontium optical clocks at an uncertainty of 5 × 10(-17) via a newly established phase-coherent frequency link connecting Paris and Braunschweig using 1,415 km of telecom fibre. The remote comparison is limited only by the instability and uncertainty of the strontium lattice clocks themselves, with negligible contributions from the optical frequency transfer...
2016: Nature Communications
https://www.readbyqxmd.com/read/27499296/mitochondrial-protein-interaction-mapping-identifies-regulators-of-respiratory-chain-function
#17
Brendan J Floyd, Emily M Wilkerson, Mike T Veling, Catie E Minogue, Chuanwu Xia, Emily T Beebe, Russell L Wrobel, Holly Cho, Laura S Kremer, Charlotte L Alston, Katarzyna A Gromek, Brendan K Dolan, Arne Ulbrich, Jonathan A Stefely, Sarah L Bohl, Kelly M Werner, Adam Jochem, Michael S Westphall, Jarred W Rensvold, Robert W Taylor, Holger Prokisch, Jung-Ja P Kim, Joshua J Coon, David J Pagliarini
Mitochondria are essential for numerous cellular processes, yet hundreds of their proteins lack robust functional annotation. To reveal functions for these proteins (termed MXPs), we assessed condition-specific protein-protein interactions for 50 select MXPs using affinity enrichment mass spectrometry. Our data connect MXPs to diverse mitochondrial processes, including multiple aspects of respiratory chain function. Building upon these observations, we validated C17orf89 as a complex I (CI) assembly factor...
August 18, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27499294/cerebellar-ataxia-and-coenzyme-q-deficiency-through-loss-of-unorthodox-kinase-activity
#18
Jonathan A Stefely, Floriana Licitra, Leila Laredj, Andrew G Reidenbach, Zachary A Kemmerer, Anais Grangeray, Tiphaine Jaeg-Ehret, Catherine E Minogue, Arne Ulbrich, Paul D Hutchins, Emily M Wilkerson, Zheng Ruan, Deniz Aydin, Alexander S Hebert, Xiao Guo, Elyse C Freiberger, Laurence Reutenauer, Adam Jochem, Maya Chergova, Isabel E Johnson, Danielle C Lohman, Matthew J P Rush, Nicholas W Kwiecien, Pankaj K Singh, Anna I Schlagowski, Brendan J Floyd, Ulrika Forsman, Pavel J Sindelar, Michael S Westphall, Fabien Pierrel, Joffrey Zoll, Matteo Dal Peraro, Natarajan Kannan, Craig A Bingman, Joshua J Coon, Philippe Isope, Hélène Puccio, David J Pagliarini
The UbiB protein kinase-like (PKL) family is widespread, comprising one-quarter of microbial PKLs and five human homologs, yet its biochemical activities remain obscure. COQ8A (ADCK3) is a mammalian UbiB protein associated with ubiquinone (CoQ) biosynthesis and an ataxia (ARCA2) through unclear means. We show that mice lacking COQ8A develop a slowly progressive cerebellar ataxia linked to Purkinje cell dysfunction and mild exercise intolerance, recapitulating ARCA2. Interspecies biochemical analyses show that COQ8A and yeast Coq8p specifically stabilize a CoQ biosynthesis complex through unorthodox PKL functions...
August 18, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27493029/the-coq2-genotype-predicts-the-severity-of-coenzyme-q10-deficiency
#19
Maria Andrea Desbats, Valeria Morbidoni, Micol Silic-Benussi, Mara Doimo, Vincenzo Ciminale, Matteo Cassina, Sabrina Sacconi, Michio Hirano, Giuseppe Basso, Fabien Pierrel, Placido Navas, Leonardo Salviati, Eva Trevisson
COQ2 (p-hydroxybenzoate polyprenyl transferase) encodes the enzyme required for the second step of the final reaction sequence of Coenzyme Q10 (CoQ) biosynthesis. Its mutations represent a frequent cause of primary CoQ deficiency and have been associated with the widest clinical spectrum, ranging from fatal neonatal multisystemic disease to late-onset encephalopathy. However, the reasons of this variability are still unknown.We have characterized the structure of human COQ2, defined its subcellular localization and developed a yeast model to validate all the mutant alleles reported so far...
August 4, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27472605/direct-laser-writing-of-a-low-loss-waveguide-with-independent-control-over-the-transverse-dimension-and-the-refractive-index-contrast-between-the-core-and-the-cladding
#20
Pascal Masselin, Eugène Bychkov, David Le Coq
In this Letter, we present the realization of a low-loss waveguide in a chalcogenide glass by direct laser writing technique in a particular configuration that allows the independent control over the diameter of the core and the magnitude of the refractive index contrast with the cladding. The waveguide is of multicore type and composed of 19 channels arranged on a hexagonal lattice. Each channel is obtained by stacking voxels of refractive index variation obtained by static exposure to femtosecond laser pulse burst...
August 1, 2016: Optics Letters
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