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Sample records for acetoacetyl coa thiolase

  1. Reverse genetic characterization of two paralogous acetoacetyl CoA thiolase genes in Arabidopsis reveals their importance in plant growth and development

    Jin, Huanan; Song, Zhihong; Nikolau, Basil J.

    2012-03-31

    Acetoacetyl CoA thiolase (AACT, EC 2.3.1.9) catalyzes the condensation of two acetyl CoA molecules to form acetoacetyl CoA. Two AACT‐encoding genes, At5g47720 (AACT1) and At5g48230 (AACT2), were functionally identified in the Arabidopsis genome by direct enzymological assays and functional expression in yeast. Promoter::GUS fusion experiments indicated that AACT1 is primarily expressed in the vascular system and AACT2 is highly expressed in root tips, young leaves, top stems and anthers. Characterization of T‐DNA insertion mutant alleles at each AACT locus established that AACT2 function is required for embryogenesis and for normal male gamete transmission. In contrast, plants lacking AACT1 function are completely viable and show no apparent growth phenotypes, indicating that AACT1 is functionally redundant with respect to AACT2 function. RNAi lines that express reduced levels of AACT2 show pleiotropic phenotypes, including reduced apical dominance, elongated life span and flowering duration, sterility, dwarfing, reduced seed yield and shorter root length. Microscopic analysis reveals that the reduced stature is caused by a reduction in cell size and fewer cells, and male sterility is caused by loss of the pollen coat and premature degeneration of the tapetal cells. Biochemical analyses established that the roots of AACT2 RNAi plants show quantitative and qualitative alterations in phytosterol profiles. These phenotypes and biochemical alterations are reversed when AACT2 RNAi plants are grown in the presence of mevalonate, which is consistent with the role of AACT2 in generating the bulk of the acetoacetyl CoA precursor required for the cytosol‐localized, mevalonate‐derived isoprenoid biosynthetic pathway.

  2. Generation of poly-β-hydroxybutyrate from acetate in higher plants: Detection of acetoacetyl CoA reductase- and PHB synthase- activities in rice.

    Tsuda, Hirohisa; Shiraki, Mari; Inoue, Eri; Saito, Terumi

    2016-08-20

    It has been reported that Poly-β-hydroxybutyrate (PHB) is generated from acetate in the rice root. However, no information is available about the biosynthetic pathway of PHB from acetate in plant cells. In the bacterium Ralstonia eutropha H16 (R. eutropha), PHB is synthesized from acetyl CoA by the consecutive reaction of three enzymes: β-ketothiolase (EC: 2.3.1.9), acetoacetyl CoA reductase (EC: 1.1.1.36) and PHB synthase (EC: 2.3.1.-). Thus, in this study, we examined whether the above three enzymatic activities were also detected in rice seedlings. The results clearly showed that the activities of the above three enzymes were all detected in rice. In particular, the PHB synthase activity was detected specifically in the sonicated particulate fractions (2000g 10min precipitate (ppt) and the 8000g 30min ppt) of rice roots and leaves. In addition to these enzyme activities, several new experimental results were obtained on PHB synthesis in higher plants: (a) (14)C-PHB generated from 2-(14)C-acetate was mainly localized in the 2000g 10min ppt and the 8000g 30min ppt of rice root. (b) Addition of acetate (0.1-10mM) to culture medium of rice seedlings did not increase the content of PHB in the rice root or leaf. (c) In addition to C3 plants, PHB was generated from acetate in a C4 plant (corn) and in a CAM plant (Bryophyllum pinnatum). d) Washing with ethylenediaminetetraacetic acid (EDTA) strongly suggested that the PHB synthesized from acetate was of plant origin and was not bacterial contamination. PMID:27372278

  3. Crystal structure of a thiolase from Escherichia coli at 1.8 Å resolution.

    Ithayaraja, M; Janardan, N; Wierenga, Rik K; Savithri, H S; Murthy, M R N

    2016-07-01

    Thiolases catalyze the Claisen condensation of two acetyl-CoA molecules to give acetoacetyl-CoA, as well as the reverse degradative reaction. Four genes coding for thiolases or thiolase-like proteins are found in the Escherichia coli genome. In this communication, the successful cloning, purification, crystallization and structure determination at 1.8 Å resolution of a homotetrameric E. coli thiolase are reported. The structure of E. coli thiolase co-crystallized with acetyl-CoA at 1.9 Å resolution is also reported. As observed in other tetrameric thiolases, the present E. coli thiolase is a dimer of two tight dimers and probably functions as a biodegradative enzyme. Comparison of the structure and biochemical properties of the E. coli enzyme with those of other well studied thiolases reveals certain novel features of this enzyme, such as the modification of a lysine in the dimeric interface, the possible oxidation of the catalytic Cys88 in the structure of the enzyme obtained in the presence of CoA and active-site hydration. The tetrameric enzyme also displays an interesting departure from exact 222 symmetry, which is probably related to the deformation of the tetramerization domain that stabilizes the oligomeric structure of the protein. The current study allows the identification of substrate-binding amino-acid residues and water networks at the active site and provides the structural framework required for understanding the biochemical properties as well as the physiological function of this E. coli thiolase. PMID:27380370

  4. Functional Expression of the Thiolase Gene thl from Clostridium beijerinckii P260 in Lactococcus lactis and Lactobacillus buchneri

    The first step of the butanol pathway involves an acetyl-CoA acetyltransferase (ACoAAT), which controls the key branching point from acetyl-CoA to butanol. ACoAAT, also known as thiolase (EC 2.3.1.9), is encoded by the thl gene and catalyzes ligation of 2 acetyl-CoA into acetoacetyl-CoA. Bioinform...

  5. Crystal structure and biochemical characterization of beta-keto thiolase B from polyhydroxyalkanoate-producing bacterium Ralstonia eutropha H16

    Highlights: • We determined a crystal structure of β-keto thiolase from Ralstonia eutropha H16 (ReBktB). • Distinct substrate binding mode ReBktB was elucidated. • Enzymatic kinetic parameters of ReBktB were revealed. - Abstract: ReBktB is a β-keto thiolase from Ralstonia eutropha H16 that catalyzes condensation reactions between acetyl-CoA with acyl-CoA molecules that contains different numbers of carbon atoms, such as acetyl-CoA, propionyl-CoA, and butyryl-CoA, to produce valuable bioproducts, such as polyhydroxybutyrate, polyhydroxybutyrate-hydroxyvalerate, and hexanoate. We solved a crystal structure of ReBktB at 2.3 Å, and the overall structure has a similar fold to that of type II biosynthetic thiolases, such as PhbA from Zoogloea ramigera (ZrPhbA). The superposition of this structure with that of ZrPhbA complexed with CoA revealed the residues that comprise the catalytic and substrate binding sites of ReBktB. The catalytic site of ReBktB contains three conserved residues, Cys90, His350, and Cys380, which may function as a covalent nucleophile, a general base, and second nucleophile, respectively. For substrate binding, ReBktB stabilized the ADP moiety of CoA in a distinct way compared to ZrPhbA with His219, Arg221, and Asp228 residues, whereas the stabilization of β-mercaptoethyamine and pantothenic acid moieties of CoA was quite similar between these two enzymes. Kinetic study of ReBktB revealed that Km, Vmax, and Kcat values of 11.58 μM, 1.5 μmol/min, and 102.18 s−1, respectively, and the catalytic and substrate binding sites of ReBktB were further confirmed by site-directed mutagenesis experiments

  6. Crystal structure of a monomeric thiolase-like protein type 1 (TLP1 from Mycobacterium smegmatis.

    Neelanjana Janardan

    Full Text Available An analysis of the Mycobacterium smegmatis genome suggests that it codes for several thiolases and thiolase-like proteins. Thiolases are an important family of enzymes that are involved in fatty acid metabolism. They occur as either dimers or tetramers. Thiolases catalyze the Claisen condensation of two acetyl-Coenzyme A molecules in the synthetic direction and the thiolytic cleavage of 3-ketoacyl-Coenzyme A molecules in the degradative direction. Some of the M. smegmatis genes have been annotated as thiolases of the poorly characterized SCP2-thiolase subfamily. The mammalian SCP2-thiolase consists of an N-terminal thiolase domain followed by an additional C-terminal domain called sterol carrier protein-2 or SCP2. The M. smegmatis protein selected in the present study, referred to here as the thiolase-like protein type 1 (MsTLP1, has been biochemically and structurally characterized. Unlike classical thiolases, MsTLP1 is a monomer in solution. Its structure has been determined at 2.7 Å resolution by the single wavelength anomalous dispersion method. The structure of the protomer confirms that the N-terminal domain has the thiolase fold. An extra C-terminal domain is indeed observed. Interestingly, it consists of six β-strands forming an anti-parallel β-barrel which is completely different from the expected SCP2-fold. Detailed sequence and structural comparisons with thiolases show that the residues known to be essential for catalysis are not conserved in MsTLP1. Consistent with this observation, activity measurements show that MsTLP1 does not catalyze the thiolase reaction. This is the first structural report of a monomeric thiolase-like protein from any organism. These studies show that MsTLP1 belongs to a new group of thiolase related proteins of unknown function.

  7. Phylogenetic analysis of the thiolase family. Implications for the evolutionary origin of peroxisomes.

    Igual, J C; González-Bosch, C; Dopazo, J; Pérez-Ortín, J E

    1992-08-01

    The thiolase family is a widespread group of proteins present in prokaryotes and three cellular compartments of eukaryotes. This fact makes this family interesting in order to study the evolutionary process of eukaryotes. Using the sequence of peroxisomal thiolase from Saccharomyces cerevisiae recently obtained by us and the other known thiolase sequences, a phylogenetic analysis has been carried out. It shows that all these proteins derived from a primitive enzyme, present in the common ancestor of eubacteria and eukaryotes, which evolved into different specialized thiolases confined to various cell compartments. The evolutionary tree obtained is compatible with the endosymbiotic theory for the origin of peroxisomes. PMID:1354266

  8. Molecular cloning, gene structure and expression profile of two mouse peroxisomal 3-ketoacyl-CoA thiolase genes

    Latruffe Norbert

    2004-03-01

    Full Text Available Abstract Background In rats, two peroxisomal 3-ketoacyl-CoA thiolase genes (A and B have been cloned, whereas only one thiolase gene is found in humans. The aim of this study was thus to clone the different mouse thiolase genes in order to study both their tissue expression and their associated enzymatic activity. Results In this study, we cloned and characterized two mouse peroxisomal 3-ketoacyl-CoA thiolase genes (termed thiolase A and B. Both thiolase A and B genes contain 12 exons and 11 introns. Using RNA extracted from mouse liver, we cloned the two corresponding cDNAs. Thiolase A and B cDNAs possess an open reading frame of 1272 nucleotides encoding a protein of 424 amino acids. In the coding sequence, the two thiolase genes exhibited ≈97% nucleotide sequence identity and ≈96% identity at the amino acid level. The tissue-specific expression of the two peroxisomal 3-ketoacyl-CoA thiolase genes was studied in mice. Thiolase A mRNA was mainly expressed in liver and intestine, while thiolase B mRNA essentially exhibited hepatic expression and weaker levels in kidney, intestine and white adipose tissue. Thiolase A and B expressions in the other tissues such as brain or muscle were very low though these tissues were chiefly involved in peroxisomal disorders. At the enzymatic level, thiolase activity was detected in liver, kidney, intestine and white adipose tissue but no significant difference was observed between these four tissues. Moreover, thiolase A and B genes were differently induced in liver of mice treated with fenofibrate. Conclusion Two mouse thiolase genes and cDNAs were cloned. Their corresponding transcripts are mostly expressed in the liver of mice and are differently induced by fenofibrate.

  9. Two different subcellular-localized Acetoacetyl-CoA acetyltransferases differentiate diverse functions in Magnaporthe oryzae.

    Zhong, Zhenhui; Norvienyeku, Justice; Yu, Jie; Chen, Meilian; Cai, Renli; Hong, Yonghe; Chen, Liqiong; Zhang, Dongmei; Wang, Baohua; Zhou, Jie; Lu, Guodong; Chen, Xiaofeng; Wang, Zonghua

    2015-10-01

    The mevalonate pathway is an efficient biosynthesis pathway that yields isoprenoids for promoting different crucial cellular functions, including ergosterol synthesis and growth regulation. Acetoacetyl-CoA acetyltransferase (EC2.3.1.9) is the first major catalytic enzyme constituting the mevalonate pathway and catalyzes the transformation of Acetoacetyl-CoA from two molecules of acetyl-CoA enroute ergosterol production in fungi. We identified two homologous genes encoding Acetoacetyl-CoA acetyltransferase (MoAcat1 and MoAcat2) in Magnaporthe oryzae, the rice blast fungus. Phylogenetic analysis indicates these two genes have different evolutionary history. We subsequently, conducted targeted gene deletion using homologous recombination technology to ascertain the unique roles of the two MoAcat homologues during the fungal morphogenesis and pathogenesis. The findings from our investigations showed that the activity of MoAcat1 promoted virulence in the rice blast fungus as such, the ΔMoacat1 mutants generated exhibited defect in virulence, whilst ΔMoacat1 mutants did not portray growth defects. ΔMoacat2 mutants on the other hand were characterized by reduction in growth and virulence. Furthermore, MoAcat1 and MoAcat2 showed different expression patterns and subcellular localizations in M. oryzae. From our investigations we came to the conclusion that, different subcellular localization contributes to the diverse functions of MoAcat1 and MoAcat2, which helps the successful establishment of blast disease by promoting efficient development of cell morphology and effective colonization of host tissue. PMID:26318870

  10. Disease: H01076 [KEGG MEDICUS

    Full Text Available abolism caused by a deficiency of mitochondrial acetoacetyl-CoA thiolase. The patients present with intermit...hemical, and clinical characterization of mitochondrial acetoacetyl-coenzyme A thiolase deficiency in two further patients

  11. Differences among Adult COAs and Adult Non-COAs on Levels of Self-Esteem, Depression, and Anxiety.

    Dodd, David T.; Roberts, Richard L.

    1994-01-01

    Examined self-esteem, depression, and anxiety among 60 adult children of alcoholics (COAs) and 143 adult non-COAs. Subjects completed Children of Alcoholics Screening Test, demographic questionnaire, Beck Depression Inventory, State-Trait Anxiety Inventory, and Coopersmith Self-Esteem Inventory. Found no significant differences between COAs and…

  12. Fatty acid oxidation in brain is limited by the low activity of 3-ketoacyl-CoA thiolase

    In an attempt to establish why the brain is virtually incapable of oxidizing fatty acids, the activities of the β-oxidation enzymes in rat brain and rat heart mitochondria were measured and compared with each other. Although the apparent K/sub m/ values and chain-length specificities of the brain and heart enzymes are similar, the specific activities of all but one brain enzyme are between 4% and 50% of those observed in heart mitochondria. The exception is 3-ketoacyl-CoA thiolase (EC 2.3.1.16) whose specific activity in brain mitochondria is 125-times lower than in heart mitochondria. The partially purified brain 3-ketoacyl-CoA thiolase was shown to be catalytically and immunologically identical with the heart enzyme. The low rate of fatty acid oxidation in brain mitochondria estimated on the basis of palmitoylcarnitine-supported respiration and [1-14C]palmitoylcarnitine degradation may be the consequence of the low activity of 3-ketoacyl-CoA thiolase. Inhibition of [1-14C]palmitoylcarnitine oxidation by 4-bromocrotonic acid proves that the observed oxidation of fatty acids in brain is dependent on 3-ketoacyl-CoA thiolase and thus occurs via β-oxidation. Since the reactions catalyzed by carnitine palmitoyltransferase (EC 2.3.1.21) and acyl-CoA synthetase (EC 6.2.1.3) do not seem to restrict fatty acid oxidation in brain, it is concluded that the oxidation of fatty acids in rat brain is limited by the activity of the mitochondrial 3-ketoacyl-CoA thiolase

  13. Characterisation of Acetyl-CoA Thiolase: The First Enzyme in the Biosynthesis of Terpenic Sex Pheromone Components in the Labial Gland of Bombus terrestris

    Brabcová, Jana; Demianová, Z.; Kindl, Jiří; Pichová, Iva; Valterová, Irena; Zarevúcka, Marie

    2015-01-01

    Roč. 16, č. 7 (2015), s. 1047-1051. ISSN 1439-4227 R&D Projects: GA TA ČR TA01020969 Institutional support: RVO:61388963 Keywords : acetyl-CoA thiolase * biosynthesis * Bombus terrestris * labial gland * pheromones * terpenoids Subject RIV: CE - Biochemistry Impact factor: 3.088, year: 2014

  14. Characterisation of Acetyl-CoA Thiolase: The First Enzyme in the Biosynthesis of Terpenic Sex Pheromone Components in the Labial Gland of Bombus terrestris.

    Brabcová, Jana; Demianová, Zuzana; Kindl, Jiří; Pichová, Iva; Valterová, Irena; Zarevúcka, Marie

    2015-05-01

    Buff-tailed bumblebees, Bombus terrestris, use a male sex pheromone for premating communication. Its main component is a sesquiterpene, 2,3-dihydrofarnesol. This paper reports the isolation of a thiolase (acetyl-CoA thiolase, AACT_BT), the first enzyme involved in the biosynthetic pathway leading to formation of isoprenoids in the B. terrestris male sex pheromone. Characterisation of AACT_BT might contribute to a better understanding of pheromonogenesis in the labial gland of B. terrestris males. The protein was purified to apparent homogeneity by column chromatography with subsequent stepwise treatment. AACT_BT showed optimum acetyltransferase activity at pH 7.1 and was strongly inhibited by iodoacetamide. The enzyme migrated as a band with an apparent mass of 42.9 kDa on SDS-PAGE. MS analysis of an AACT_BT tryptic digest revealed high homology to representatives of the thiolase family. AACT_BT has 96 % amino acid sequence identity with the previously reported Bombus impatiens thiolase. PMID:25801592

  15. COA based robust output feedback UPFC controller design

    In this paper, a novel method for the design of output feedback controller for unified power flow controller (UPFC) using chaotic optimization algorithm (COA) is developed. Chaotic optimization algorithms, which have the features of easy implementation, short execution time and robust mechanisms of escaping from the local optimum, is a promising tool for the engineering applications. The selection of the output feedback gains for the UPFC controllers is converted to an optimization problem with the time domain-based objective function which is solved by a COA based on Lozi map. Since chaotic mapping enjoys certainty, ergodicity and the stochastic property, the proposed chaotic optimization problem introduces chaos mapping using Lozi map chaotic sequences which increases its convergence rate and resulting precision. To ensure the robustness of the proposed stabilizers, the design process takes into account a wide range of operating conditions and system configurations. The effectiveness of the proposed controller for damping low frequency oscillations is tested and demonstrated through non-linear time-domain simulation and some performance indices studies. The results analysis reveals that the designed COA based output feedback UPFC damping controller has an excellent capability in damping power system low frequency oscillations and enhance greatly the dynamic stability of the power systems.

  16. Identification of a novel CoA synthase isoform, which is primarily expressed in Brain

    CoA and its derivatives Acetyl-CoA and Acyl-CoA are important players in cellular metabolism and signal transduction. CoA synthase is a bifunctional enzyme which mediates the final stages of CoA biosynthesis. In previous studies, we have reported molecular cloning, biochemical characterization, and subcellular localization of CoA synthase (CoASy). Here, we describe the existence of a novel CoA synthase isoform, which is the product of alternative splicing and possesses a 29aa extension at the N-terminus. We termed it CoASy β and originally identified CoA synthase, CoASy α. The transcript specific for CoASy β was identified by electronic screening and by RT-PCR analysis of various rat tissues. The existence of this novel isoform was further confirmed by immunoblot analysis with antibodies directed to the N-terminal peptide of CoASy β. In contrast to CoASy α, which shows ubiquitous expression, CoASy β is primarily expressed in Brain. Using confocal microscopy, we demonstrated that both isoforms are localized on mitochondria. The N-terminal extension does not affect the activity of CoA synthase, but possesses a proline-rich sequence which can bring the enzyme into complexes with signalling proteins containing SH3 or WW domains. The role of this novel isoform in CoA biosynthesis, especially in Brain, requires further elucidation

  17. Mosaic Conservation Opportunity Areas - Liberal Model (ECO_RES.COA_MOSAIC33)

    U.S. Environmental Protection Agency — The COA_Mosaic33 layer designates areas with potential for forest/grassland mosaic conservation. These are areas of natural or semi-natural forest/grassland mosaic...

  18. Cryogenic Optical Assembly (COA) cooldown analysis for the Cosmic Background Explorer (COBE)

    Coladonato, Robert J.; Irish, Sandra M.; Mosier, Carol L.

    1990-01-01

    The Cosmic Background Explorer (COBE) spacecraft, developed by Goddard Space Flight Center (GSFC), was successfully launched on November 18, 1989 aboard a Delta expendable launch vehicle. Two of the three instruments for this mission were mounted inside a liquid helium (LHe) dewar which operates at a temperature of 2 K. These two instruments are the Diffuse Infrared Background Experiment (DIRBE) and the Far Infrared Absolute Spectrophotometer (FIRAS). They are mounted to a common Instrument Interface Structure (IIS) and the entire assembly is called the Cryogenic Optical Assembly (COA). As part of the structural verification requirement, it was necessary to show that the entire COA exhibited adequate strength and would be capable of withstanding the launch environment. This requirement presented an unique challenge for COBE because the COA is built and assembled at room temperature (300 K), cooled to 2 K, and then subjected to launch loads. However, strength testing of the entire COA at 2 K could not be done because of facility limitations. Therefore, it was decided to perform the strength verification of the COA by analysis.

  19. Effect of elevated total CoA levels on metabolic pathways in cultured hepatocytes

    Livers from fasted rats have 30% higher total CoA levels than fed rats. To determine whether this increase of total CoA influences metabolism, the rates of gluconeogenesis, fatty acid oxidation and ketogenesis were measured in hepatocytes with cyanamide (CYM) or pantothenate (PA) deficient medium used to vary total CoA levels independently of hormonal status. Primary cultures of rat hepatocytes were incubated 14 hrs with Bt2 cAMP, dexamethasone + theophylline in PA deficient medium or with CYM (500 μM) + PA, rinsed and preincubated 0.5 hr to remove the CYM. Hepatocytes treated with CYM had total CoA levels 10-24% higher than PA deficient cells and lower rates of glucose production from lactate + pyruvate (L/P) or from alanine (0.23 +/- 0.05 and 0.089 +/- 0.02 μm/mg protein, respectively in CYM treated cells compared to 0.33 +/- 0.06 and 0.130 +/- 0.006 in PA deficient cells). This decrease was not due to CYM per se, as the direct addition of CYM stimulated glucose production from L/P. CYM treated cells with 15-40% higher total CoA and 30% higher fatty acyl-CoA levels had the same rates of [14C]-palmitate oxidation as PA deficient cells. However, rates of ketogenesis were lower in CYM treated cells (163 +/- 11 nm/mg compared to 217 +/- 14 nm/mg protein). These results suggest that physiological alterations of hepatic total CoA levels are not necessary for fasting rates of gluconeogenesis, fatty acid oxidation and ketogenesis

  20. The COA360: a tool for assessing the cultural competency of healthcare organizations.

    LaVeist, Thomas A; Relosa, Rachel; Sawaya, Nadia

    2008-01-01

    The U.S. Census Bureau projects that by 2050, non-Hispanic whites will be in the numerical minority. This rapid diversification requires healthcare organizations to pay closer attention to cross-cultural issues if they are to meet the healthcare needs of the nation and continue to maintain a high standard of care. Although scorecards and benchmarking are widely used to gauge healthcare organizations' performance in various areas, these tools have been underused in relation to cultural preparedness or initiatives. The likely reason for this is the lack of a validated tool specifically designed to examine cultural competency. Existing validated cultural competency instruments evaluate individuals, not organizations. In this article, we discuss a study to validate the Cultural Competency Organizational Assessment--360 or the COA360, an instrument designed to appraise a healthcare organization's cultural competence. The Office of Minority Health and the Joint Commission have each developed standards for measuring the cultural competency of organizations. The COA360 is designed to assess adherence to both of these sets of standards. For this validation study, we enlisted a panel of national experts. The panel rated each dimension of the COA360, and the combination of items for each of the scale's 14 dimensions was rated above 4.13 (on 5-point scale). Our conclusion points to the validity of the COA360. As such, it is a valuable tool not only for assessing a healthcare organization's cultural readiness but also for benchmarking its progress in addressing cultural and diversity issues. PMID:18720687

  1. Kinetic properties and inhibition of Trypanosoma cruzi 3-hydroxy-3-methylglutaryl CoA reductase

    Hurtado-Guerrrero, Ramón; Pena Diaz, Javier; Montalvetti, Andrea; Ruiz-Pérez, Luis M; González-Pacanowska, Dolores

    2002-01-01

    A detailed kinetic analysis of the recombinant soluble enzyme 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) from Trypanosoma cruzi has been performed. The enzyme catalyzes the normal anabolic reaction and the reductant is NADPH. It also catalyzes the oxidation of mevalonate but at a lower propo...

  2. Liver fatty acid binding protein (LFABP) transfers fatty acids and fatty acyl coas to membranes

    De Gerónimo, Eduardo; Hagan, Robert M; Wilton, David C.; Córsico, Betina

    2010-01-01

    The objective of this work was to analyze LFABP´s capacity to transfer acyl CoAs to artificial membranes and compare it to LCFA transfer employing natural ligands, in order to better understand the specific physiological role of LFABP in the cell.

  3. CoaSim: A Flexible Environment for Simulating Genetic Data under Coalescent Models

    Mailund; Schierup, Mikkel Heide; Pedersen, Christian Nørgaard Storm;

    2005-01-01

    get insight into these. Results We have created the CoaSim application as a flexible environment for Monte various types of genetic data under equilibrium and non-equilibrium coalescent variety of applications. Interaction with the tool is through the Guile version scripting language. Scheme scripts...

  4. Model simulations of cooking organic aerosol (COA) over the UK using estimates of emissions based on measurements at two sites in London

    Ots, Riinu; Vieno, Massimo; Allan, James D.; Reis, Stefan; Nemitz, Eiko; Young, Dominique E.; Coe, Hugh; Marco, Chiara; Detournay, Anais; MacKenzie, Ian A; Green, David C.; Heal, Mathew R.

    2016-01-01

    Cooking organic aerosol (COA) is currently not included in European emission inventories. However, recent positive matrix factorization (PMF) analyses of aerosol mass spectrometer (AMS) measurements have suggested important contributions of COA in several European cities. In this study, emissions of COA were estimated for the UK, based on hourly AMS measurements of COA made at two sites in London (a kerbside site in central London and an urban background site in a residential area close to ce...

  5. Intracellular signal transduction of PBAN action in the silkworm, Bombyx mori: involvement of acyl CoA reductase.

    Ozawa, R; Matsumoto, S

    1996-03-01

    In the silkworm, Bombyx mori, production of the sex pheromone bombykol is regulated by a neurohormone termed PBAN. We have detected the activity of acyl CoA reductase in the pheromone gland of B. mori by using palmitoyl CoA as a substrate. The acyl CoA reductase requires NADPH, but not NADH, as a proton dono. When the pheromone gland was incubated with the PBAN fragment peptide TKYFSPRLamide, palmitoyl CoA was incorporated and converted into the corresponding C16 alcohols. Radio HPLC analysis revealed that these C16 alcohols were hexadecan-1-ol (81.2%), (Z)-11-hexadecen-1-ol (12.3%), and (E, Z)-10, 12-hexadecadien-1-ol (= bombykol, 6.5%). The production of C16 alcohols in the pheromone gland was inhibited by the known bombykol biosynthesis inhibitors EDTA, LaCl3, W-7, trifluoperazine, p-nitrophenyl phosphate, NaF and compactin. By contrast, when the pheromone gland homogenate was incubated in the presence of palmitoyl CoA and NADPH, production of C16 alcohols was affected by compactin, W-7 and trifluoperazine, but not by EDTA, LaCl3, p-nitrophenyl phosphate and NaF. These results indicate that compactin, W-7 and trifluoperazine directly suppress the step catalyzed by acyl CoA reductase, whereas EDTA, LaCl3, pNPP, and NaF inhibit bombykol production by affecting other biochemical steps in the signal transduction of PBAN action. The present results also imply that PBAN regulates the step catalyzed by acyl CoA reductase and that palmitoyl CoA could be used as a substrate of the acyl CoA reductase that regulates bombykol biosynthesis. PMID:8900596

  6. Treatment with the 3-ketoacyl-CoA thiolase inhibitor trimetazidine does not exacerbate whole-body insulin resistance in obese mice.

    Ussher, John R; Keung, Wendy; Fillmore, Natasha; Koves, Timothy R; Mori, Jun; Zhang, Liyan; Lopaschuk, David G; Ilkayeva, Olga R; Wagg, Cory S; Jaswal, Jagdip S; Muoio, Deborah M; Lopaschuk, Gary D

    2014-06-01

    There is a growing need to understand the underlying mechanisms involved in the progression of cardiovascular disease during obesity and diabetes. Although inhibition of fatty acid oxidation has been proposed as a novel approach to treat ischemic heart disease and heart failure, reduced muscle fatty acid oxidation rates may contribute to the development of obesity-associated insulin resistance. Our aim was to determine whether treatment with the antianginal agent trimetazidine, which inhibits fatty acid oxidation in the heart secondary to inhibition of 3-ketoacyl-CoA thiolase (3-KAT), may have off-target effects on glycemic control in obesity. We fed C57BL/6NCrl mice a high-fat diet (HFD) for 10 weeks before a 22-day treatment with the 3-KAT inhibitor trimetazidine (15 mg/kg per day). Insulin resistance was assessed via glucose/insulin tolerance testing, and lipid metabolite content was assessed in gastrocnemius muscle. Trimetazidine-treatment led to a mild shift in substrate preference toward carbohydrates as an oxidative fuel source in obese mice, evidenced by an increase in the respiratory exchange ratio. This shift in metabolism was accompanied by an accumulation of long-chain acyl-CoA and a trend to an increase in triacylglycerol content in gastrocnemius muscle, but did not exacerbate HFD-induced insulin resistance compared with control-treated mice. It is noteworthy that trimetazidine treatment reduced palmitate oxidation rates in the isolated working mouse heart and neonatal cardiomyocytes but not C2C12 skeletal myotubes. Our findings demonstrate that trimetazidine therapy does not adversely affect HFD-induced insulin resistance, suggesting that treatment with trimetazidine would not worsen glycemic control in obese patients with angina. PMID:24700885

  7. A Chemo-Enzymatic Road Map to the Synthesis of CoA Esters

    Dominik M. Peter

    2016-04-01

    Full Text Available Coenzyme A (CoA is a ubiquitous cofactor present in every known organism. The thioesters of CoA are core intermediates in many metabolic processes, such as the citric acid cycle, fatty acid biosynthesis and secondary metabolism, including polyketide biosynthesis. Synthesis of CoA-thioesters is vital for the study of CoA-dependent enzymes and pathways, but also as standards for metabolomics studies. In this work we systematically tested five chemo-enzymatic methods for the synthesis of the three most abundant acyl-CoA thioester classes in biology; saturated acyl-CoAs, α,β-unsaturated acyl-CoAs (i.e., enoyl-CoA derivatives, and α-carboxylated acyl-CoAs (i.e., malonyl-CoA derivatives. Additionally we report on the substrate promiscuity of three newly described acyl-CoA dehydrogenases that allow the simple conversion of acyl-CoAs into enoyl-CoAs. With these five methods, we synthesized 26 different CoA-thioesters with a yield of 40% or higher. The CoA esters produced range from short- to long-chain, include branched and α,β-unsaturated representatives as well as other functional groups. Based on our results we provide a general guideline to the optimal synthesis method of a given CoA-thioester in respect to its functional group(s and the commercial availability of the precursor molecule. The proposed synthetic routes can be performed in small scale and do not require special chemical equipment, making them convenient also for biological laboratories.

  8. A Chemo-Enzymatic Road Map to the Synthesis of CoA Esters.

    Peter, Dominik M; Vögeli, Bastian; Cortina, Niña Socorro; Erb, Tobias J

    2016-01-01

    Coenzyme A (CoA) is a ubiquitous cofactor present in every known organism. The thioesters of CoA are core intermediates in many metabolic processes, such as the citric acid cycle, fatty acid biosynthesis and secondary metabolism, including polyketide biosynthesis. Synthesis of CoA-thioesters is vital for the study of CoA-dependent enzymes and pathways, but also as standards for metabolomics studies. In this work we systematically tested five chemo-enzymatic methods for the synthesis of the three most abundant acyl-CoA thioester classes in biology; saturated acyl-CoAs, α,β-unsaturated acyl-CoAs (i.e., enoyl-CoA derivatives), and α-carboxylated acyl-CoAs (i.e., malonyl-CoA derivatives). Additionally we report on the substrate promiscuity of three newly described acyl-CoA dehydrogenases that allow the simple conversion of acyl-CoAs into enoyl-CoAs. With these five methods, we synthesized 26 different CoA-thioesters with a yield of 40% or higher. The CoA esters produced range from short- to long-chain, include branched and α,β-unsaturated representatives as well as other functional groups. Based on our results we provide a general guideline to the optimal synthesis method of a given CoA-thioester in respect to its functional group(s) and the commercial availability of the precursor molecule. The proposed synthetic routes can be performed in small scale and do not require special chemical equipment, making them convenient also for biological laboratories. PMID:27104508

  9. A Clinical Study to Validate the Pupil Rescaling Technique by using COAS Shack Hartmann Aberrometer.

    Kalikivayi, V; Kannan, K; Ganesan, A R

    2015-01-01

    In any optical system, optical aberrations of the imaging system affect the image quality. The human eye is also like an optical system which has optical aberrations influencing the quality of the retinal image. When pupil size exceeds 3 mm, ocular aberrations increase and play a major role on retinal image degradation. Pupil diameter is made constant in commercially available aberrometers by mathematically rescaling it. The aim of this study is to validate the pupil rescaling technique by using COAS (Complete Ophthalmic Analysis System)Shack Hartmann Aberrometer. Five subjects were recruited for this study. The measurements were taken over a moderately large pupil of 5mm in normal room illumination to allow for natural pupil dilation. The analyses diameter is fixed at 5 mm in COAS which means it rescales the aberration data to 5 mm if the pupil diameter recorded was more than 5 mm at the time of measurement. Ocular aberrations for natural and rescaled pupil sizes were analyzed. Estimation of ocular aberrations showed there was no statistical significance between natural pupil and rescaled pupil diameter. PMID:25996727

  10. Flexible DAQ card for detector systems utilizing the CoaXPress communication standard

    This work concerns the design and construction of a flexible FPGA based data acquisition system aimed for particle detectors. The interface card as presented was designed for large area detectors with millions of individual readout channels. Flexibility was achieved by partitioning the design into multiple PCBs, creating a set of modular blocks, allowing the creation of a wide variety of configurations by simply stacking functional PCBs together. This way the user can easily toggle the polarity of the high voltage bias supply or switch the downstream interface from CoaXPress to PCIe or stream directly HDMI. We addressed the issues of data throughput, data buffering, bias voltage generation, trigger timing and fine tuning of the whole readout chain enabling a smooth data transmission. On the current prototype, we have wire-bonded a MediPix2 MXR quad and connected it to a XILINX FPGA. For the downstream interface, we implemented the CoaXPress communication protocol, which enables us to stream data at 3.125 Gbps to a standard PC

  11. Purification, gene cloning, and characterization of γ-butyrobetainyl CoA synthetase from Agrobacterium sp. 525a.

    Fujimitsu, Hiroshi; Matsumoto, Akira; Takubo, Sayaka; Fukui, Akiko; Okada, Kazuma; Mohamed Ahmed, Isam A; Arima, Jiro; Mori, Nobuhiro

    2016-08-01

    The report is the first of purification, overproduction, and characterization of a unique γ-butyrobetainyl CoA synthetase from soil-isolated Agrobacterium sp. 525a. The primary structure of the enzyme shares 70-95% identity with those of ATP-dependent microbial acyl-CoA synthetases of the Rhizobiaceae family. As distinctive characteristics of the enzyme of this study, ADP was released in the catalytic reaction process, whereas many acyl CoA synthetases are annotated as an AMP-forming enzyme. The apparent Km values for γ-butyrobetaine, CoA, and ATP were, respectively, 0.69, 0.02, and 0.24 mM. PMID:27125317

  12. Structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase in complex with the feedback inhibitor CoA reveals only one active-site conformation

    The X-ray structure of phosphopantetheine adenylyltransferase (PPAT) from M. tuberculosis in complex with its feedback regulator coenzyme A (CoA) was determined to 2.11 Å resolution. Unlike previous X-ray structures of PPAT–CoA complexes from other bacteria, which showed two distinct conformations of bound CoA, only one conformation of bound CoA is observed in the M. tuberculosis PPAT–CoA complex. Phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in the coenzyme A (CoA) biosynthetic pathway, reversibly transferring an adenylyl group from ATP to 4′-phosphopantetheine to form dephosphocoenzyme A (dPCoA). To complement recent biochemical and structural studies on Mycobacterium tuberculosis PPAT (MtPPAT) and to provide further insight into the feedback regulation of MtPPAT by CoA, the X-ray crystal structure of the MtPPAT enzyme in complex with CoA was determined to 2.11 Å resolution. Unlike previous X-ray crystal structures of PPAT–CoA complexes from other bacteria, which showed two distinct CoA conformations bound to the active site, only one conformation of CoA is observed in the MtPPAT–CoA complex

  13. Structure of Mycobacterium tuberculosis phosphopantetheine adenylyltransferase in complex with the feedback inhibitor CoA reveals only one active-site conformation

    Wubben, T.; Mesecar, A.D. (Purdue); (UIC)

    2014-10-02

    Phosphopantetheine adenylyltransferase (PPAT) catalyzes the penultimate step in the coenzyme A (CoA) biosynthetic pathway, reversibly transferring an adenylyl group from ATP to 4'-phosphopantetheine to form dephosphocoenzyme A (dPCoA). To complement recent biochemical and structural studies on Mycobacterium tuberculosis PPAT (MtPPAT) and to provide further insight into the feedback regulation of MtPPAT by CoA, the X-ray crystal structure of the MtPPAT enzyme in complex with CoA was determined to 2.11 {angstrom} resolution. Unlike previous X-ray crystal structures of PPAT-CoA complexes from other bacteria, which showed two distinct CoA conformations bound to the active site, only one conformation of CoA is observed in the MtPPAT-CoA complex.

  14. Acetyl CoA Carboxylase 2 Is Dispensable for CD8+ T Cell Responses.

    Jang Eun Lee

    Full Text Available Differentiation of T cells is closely associated with dynamic changes in nutrient and energy metabolism. However, the extent to which specific metabolic pathways and molecular components are determinative of CD8+ T cell fate remains unclear. It has been previously established in various tissues that acetyl CoA carboxylase 2 (ACC2 regulates fatty acid oxidation (FAO by inhibiting carnitine palmitoyltransferase 1 (CPT1, a rate-limiting enzyme of FAO in mitochondria. Here, we explore the cell-intrinsic role of ACC2 in T cell immunity in response to infections. We report here that ACC2 deficiency results in a marginal increase of cellular FAO in CD8+ T cells, but does not appear to influence antigen-specific effector and memory CD8+ T cell responses during infection with listeria or lymphocytic choriomeningitis virus. These results suggest that ACC2 is dispensable for CD8+ T cell responses.

  15. COA2帮软件轻松换新家

    Sportsman

    2003-01-01

    Windows体积越来越大,而且在使用中还会不断膨胀自己,大部分软件也会默认安装在 文件夹中,时间一长,原来宽敞的C盘变得拥剂不堪,那么该如给C盘减肥呢?除到除临时文件等方法外,为什么不把原来装在C盘上的软件战略转移到其他分区?而COA2可以让你无需卸载和重装软件,直接将软件目录剪切到其他分区,从而完成快速搬家工程。

  16. Carnitine palmitoyl transferase activity in Morris Hepatoma 7777 mitochondria and its sensitivity to malonyl CoA inhibition

    Earlier reports in the literature have indicated no detectable Carnitine Palymitoyl Transferase (CPT) activity in homogenates prepared from Morris Hepatoma 7777. In its study CPT activity in isolated mitochondria (mito) was measured by butanol extraction of the [3H]palmitoyl carnitine formed as outlined by Bremer et al. Contrary to the earlier work where no appreciable activity of CPT was observed the authors find significant levels of CPT (2.6 nMol/min/mg protein) in isolated mito from Morris Hepatoma 7777 (MH 7777). The level of CPT activity observed in MH 7777 mito was, however, 36% lower compared to the host liver CPT activity (4.1 nMol/min/mg protein). The enzyme in MH 7777 mito showed 83% inhibition in the presence of 10 μM malonyl CoA, in agreement with the degree of sensitivity observed with the host liver isolated mito. On freeze thawing host mito, total CPT activity increased and the sensitivity of the enzyme to malonyl CoA decreased. Frozen thawed MH 7777 mito showed a similar response to malonyl CoA but no change in the total CPT level was observed. The authors results establish for the first time the presence of a malonyl CoA sensitive CPT in MH 7777 mito, which may have slightly different properties from normal due to the membrane environment of the enzyme

  17. Inhibition of neutral lipase from castor bean lipid bodies by coenzyme A (CoA) and Oleoyl-CoA

    The neutral lipase (EC 3.1.1.3) in lipid body membranes isolated from the endosperm of 4 day old castor (Ricinus communis L.) seedlings catalyzes the hydrolysis of [14C]trioleoylglycerol, releasing [14C]oleic acid for up to 4 hours. However, the addition of Mg-ATP and coenzyme A (CoA), which are present in the cytoplasm of plant cells, caused a progressive inhibition of the neutral lipase such that after 15 minutes, release of [14C]oleic acid was almost undetectable. A fatty acyl CoA synthetase was found in the lipid body membrane which converts [14C]oleic acid produced from the lipase reaction to [14C]oleoyl-CoA under these conditions. The concentration of free oleoyl-CoA in the reaction mixture when the lipase was inhibited by 50% was calculated to be about 21 micromolar. It was found that a mixture of exogenously added oleoyl-CoA and CoA was most effective in causing lipase inhibition. Little inhibition of lipase was detected in the presence of CoA alone. It is possible that this effect is important in vivo in coordinating lipase activity with fatty acid oxidation

  18. SIRT3 deacetylates mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 and regulates ketone body production

    Shimazu, Tadahiro; Hirschey, Matthew D; Hua, Lan; Dittenhafer-Reed, Kristin E; Schwer, Bjoern; Lombard, David B; Li, Yu; Bunkenborg, Jakob; Alt, Frederick W; Denu, John M; Jacobson, Matthew P; Verdin, Eric

    2010-01-01

    The mitochondrial sirtuin SIRT3 regulates metabolic homeostasis during fasting and calorie restriction. We identified mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase 2 (HMGCS2) as an acetylated protein and a possible target of SIRT3 in a proteomics survey in hepatic mitochondria from Sirt3(...

  19. Toxicity of Carboxylic Acid-Containing Drugs: The Role of Acyl Migration and CoA Conjugation Investigated.

    Lassila, Toni; Hokkanen, Juho; Aatsinki, Sanna-Mari; Mattila, Sampo; Turpeinen, Miia; Tolonen, Ari

    2015-12-21

    Many carboxylic acid-containing drugs are associated with idiosyncratic drug toxicity (IDT), which may be caused by reactive acyl glucuronide metabolites. The rate of acyl migration has been earlier suggested as a predictor of acyl glucuronide reactivity. Additionally, acyl Coenzyme A (CoA) conjugates are known to be reactive. Here, 13 drugs with a carboxylic acid moiety were incubated with human liver microsomes to produce acyl glucuronide conjugates for the determination of acyl glucuronide half-lives by acyl migration and with HepaRG cells to monitor the formation of acyl CoA conjugates, their further conjugate metabolites, and trans-acylation products with glutathione. Additionally, in vitro cytotoxicity and mitochondrial toxicity experiments were performed with HepaRG cells to compare the predictability of toxicity. Clearly, longer acyl glucuronide half-lives were observed for safe drugs compared to drugs that can cause IDT. Correlation between half-lives and toxicity classification increased when "relative half-lives," taking into account the formation of isomeric AG-forms due to acyl migration and eliminating the effect of hydrolysis, were used instead of plain disappearance of the initial 1-O-β-AG-form. Correlation was improved further when a daily dose of the drug was taken into account. CoA and related conjugates were detected primarily for the drugs that have the capability to cause IDT, although some exceptions to this were observed. Cytotoxicity and mitochondrial toxicity did not correlate to drug safety. On the basis of the results, the short relative half-life of the acyl glucuronide (high acyl migration rate), high daily dose and detection of acyl CoA conjugates, or further metabolites derived from acyl CoA together seem to indicate that carboxylic acid-containing drugs have a higher probability to cause drug-induced liver injury (DILI). PMID:26558897

  20. Exome Sequence Reveals Mutations in CoA Synthase as a Cause of Neurodegeneration with Brain Iron Accumulation

    Dusi, Sabrina; Valletta, Lorella; Haack, Tobias B.; Tsuchiya, Yugo; Venco, Paola; Pasqualato, Sebastiano; Goffrini, Paola; Tigano, Marco; Demchenko, Nikita; Wieland, Thomas; Schwarzmayr, Thomas; Strom, Tim M; Invernizzi, Federica; Garavaglia, Barbara; Gregory, Allison

    2014-01-01

    Neurodegeneration with brain iron accumulation (NBIA) comprises a clinically and genetically heterogeneous group of disorders with progressive extrapyramidal signs and neurological deterioration, characterized by iron accumulation in the basal ganglia. Exome sequencing revealed the presence of recessive missense mutations in COASY, encoding coenzyme A (CoA) synthase in one NBIA-affected subject. A second unrelated individual carrying mutations in COASY was identified by Sanger sequence analys...

  1. Germline Deletion of Pantothenate Kinases 1 and 2 Reveals the Key Roles for CoA in Postnatal Metabolism

    Garcia, Matthew; Leonardi, Roberta; Zhang, Yong-Mei; Rehg, Jerold E.; Jackowski, Suzanne

    2012-01-01

    Pantothenate kinase (PanK) phosphorylates pantothenic acid (vitamin B5) and controls the overall rate of coenzyme A (CoA) biosynthesis. Pank1 gene deletion in mice results in a metabolic phenotype where fatty acid oxidation and gluconeogenesis are impaired in the fasted state, leading to mild hypoglycemia. Inactivating mutations in the human PANK2 gene lead to childhood neurodegeneration, but Pank2 gene inactivation in mice does not elicit a phenotype indicative of the neuromuscular symptoms ...

  2. The development of the 2, 4-dienoyl CoA reductase 1 gene (DECR 1) in pig

    2007-01-01

    2,4-dienoyl CoA reductase gene (DECR 1) is mapped on pig 4 q1.2, includes ten exons and nine introns of variable sizethat span 30 kb. DECR 1 gene participates in the β-oxidation pathway, affects the content of intramuscular fatty acid, especially thepercentage of linoleic acid. The expression of DECR 1 gene has important influence on IMF, the pH, and the meat colour of pork,further affects the meat quality.

  3. Molecular analysis of virulent genes (coa and spa) of staphylococcus aureus involved in natural cases of bovine mastitis

    The present study was undertaken to determine the distribution and genotypic characteristics of Staphylococcus aureus isolates recovered from naturally occurring mastitis in cattle and buffaloes. For this purpose a total of 1445 lactating cattle (653) and buffaloes (792) present at two experimental livestock farms Okara (Bahadarnagar) and Sahiwal (Qadiarabad), in and around district Faisalabad and slaughtered at an abattoir due to low milk yield and were screened for mastitis. California Mastitis Test (CMT) was used to detect sub clinical mastitis. The positive quarter milk samples were collected for culturing of S. aureus isolates. taphylococcus aureus isolates were identified on the basis of growth features, biochemical characteristics, coagulase test and as well as amplification of coagulase (coa) and spa (spa-X) genes specific to its virulence. S. aureus isolates (n=265) were characterized by Polymerase chain reaction to determine the frequency of coagulase (coa) and spa (spa-X) genes. From these isolates the amplification of the coagulase (coa) gene yielded three different PCR products approximately 204bp to 490bp while spa (spa-X) gene produced five different products ranging in size from 190bp to 320bp. PCR revealed that from all the coagulase positive S. aureus isolates 261(98.5%) had spa (spa-X) gene. The results of the present study indicated that S. aureus isolates recovered from bovine mastitis were genetically different within and among the various herds which may provide essential and valuable strategies to control staphylococcal infections in future. (author)

  4. On O(1S) and CO(a3Π) production from electron impact dissociation of CO2

    A novel method is employed to selectively detect O(1S) and CO(a 3Π) fragments following the dissociation of CO2 by electron impact. O(1S) atoms impinging on solid Xe produce a prominent emission feature at 725 nm, and less intense features at 375 and 550 nm. CO(a 3Π) molecules give a single emission feature spanning 250 to 350 nm. Time-of-flight spectra are presented for O(1S) and CO(a 3Π) from electron impact dissociation of CO2. The results for O(1S) production indicate contributions from pre-dissociation of excited states of CO2. Relative cross sections for the production of both species have been obtained. The cross section for O(1S) production has been made absolute by comparison with production of the same species from N2O. It has a threshold at 11.0 ± 0.5 eV and reaches a maximum of 1.69 x 10-17 cm2 at 50 eV. (author)

  5. Intracellular long-chain acyl CoAs activate TRPV1 channels.

    Yi Yu

    Full Text Available TRPV1 channels are an important class of membrane proteins that play an integral role in the regulation of intracellular cations such as calcium in many different tissue types. The anionic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2 is a known positive modulator of TRPV1 channels and the negatively charged phosphate groups interact with several basic amino acid residues in the proximal C-terminal TRP domain of the TRPV1 channel. We and other groups have shown that physiological sub-micromolar levels of long-chain acyl CoAs (LC-CoAs, another ubiquitous anionic lipid, can also act as positive modulators of ion channels and exchangers. Therefore, we investigated whether TRPV1 channel activity is similarly regulated by LC-CoAs. Our results show that LC-CoAs are potent activators of the TRPV1 channel and interact with the same PIP2-binding residues in TRPV1. In contrast to PIP2, LC-CoA modulation of TRPV1 is independent of Ca2+i, acting in an acyl side-chain saturation and chain-length dependent manner. Elevation of LC-CoAs in intact Jurkat T-cells leads to significant increases in agonist-induced Ca2+i levels. Our novel findings indicate that LC-CoAs represent a new fundamental mechanism for regulation of TRPV1 channel activity that may play a role in diverse cell types under physiological and pathophysiological conditions that alter fatty acid transport and metabolism such as obesity and diabetes.

  6. Software interface for high-speed readout of particle detectors based on the CoaXPress communication standard

    Hejtmánek, M.; Neue, G.; Voleš, P.

    2015-06-01

    This article is devoted to the software design and development of a high-speed readout application used for interfacing particle detectors via the CoaXPress communication standard. The CoaXPress provides an asymmetric high-speed serial connection over a single coaxial cable. It uses a widely available 75 Ω BNC standard and can operate in various modes with a data throughput ranging from 1.25 Gbps up to 25 Gbps. Moreover, it supports a low speed uplink with a fixed bit rate of 20.833 Mbps, which can be used to control and upload configuration data to the particle detector. The CoaXPress interface is an upcoming standard in medical imaging, therefore its usage promises long-term compatibility and versatility. This work presents an example of how to develop DAQ system for a pixel detector. For this purpose, a flexible DAQ card was developed using the XILINX Spartan 6 FPGA. The DAQ card is connected to the framegrabber FireBird CXP6 Quad, which is plugged in the PCI Express bus of the standard PC. The data transmission was performed between the FPGA and framegrabber card via the standard coaxial cable in communication mode with a bit rate of 3.125 Gbps. Using the Medipix2 Quad pixel detector, the framerate of 100 fps was achieved. The front-end application makes use of the FireBird framegrabber software development kit and is suitable for data acquisition as well as control of the detector through the registers implemented in the FPGA.

  7. Software interface for high-speed readout of particle detectors based on the CoaXPress communication standard

    This article is devoted to the software design and development of a high-speed readout application used for interfacing particle detectors via the CoaXPress communication standard. The CoaXPress provides an asymmetric high-speed serial connection over a single coaxial cable. It uses a widely available 75 Ω BNC standard and can operate in various modes with a data throughput ranging from 1.25 Gbps up to 25 Gbps. Moreover, it supports a low speed uplink with a fixed bit rate of 20.833 Mbps, which can be used to control and upload configuration data to the particle detector. The CoaXPress interface is an upcoming standard in medical imaging, therefore its usage promises long-term compatibility and versatility. This work presents an example of how to develop DAQ system for a pixel detector. For this purpose, a flexible DAQ card was developed using the XILINX Spartan 6 FPGA. The DAQ card is connected to the framegrabber FireBird CXP6 Quad, which is plugged in the PCI Express bus of the standard PC. The data transmission was performed between the FPGA and framegrabber card via the standard coaxial cable in communication mode with a bit rate of 3.125 Gbps. Using the Medipix2 Quad pixel detector, the framerate of 100 fps was achieved. The front-end application makes use of the FireBird framegrabber software development kit and is suitable for data acquisition as well as control of the detector through the registers implemented in the FPGA

  8. Partial genetic characterization of Stearoyl Coa-Desaturase´s structural region in Bubalus bubalis

    R.B. Thomazine

    2010-02-01

    Full Text Available Conjugated Linoleic Acids (CLAs comprise a family of positional and geometric isomers of linoleic acid. The main form of CLA, cis-9, trans-11-C18:2 show positive effects in cancer prevention and treatment. The major dietary sources of these fatty acids are derived from ruminant animals, in particular dairy products. In these animals, the endogenous synthesis mainly occurs in mammary gland by the action of enzyme Stearoyl CoA Desaturase (SCD. Different levels of expression and activity of SCD in mammary gland can explain partially the variation of CLA levels in fat milk. Considering a great fat concentration in bubaline milk and the benefit of a high and positive correlation between fat milk and CLA production, this study was carried on with the intention of sequencing and characterizing part of the gene that codifies SCD in buffaloes. Genomic DNA was extracted from blood samples of lactating bubaline which begins to the breed Murrah. After the (acho que nao precisa desse the extractions, PCR (Polymerase Chain Reaction reactions were made by using primers Z43D1 and E143F1. The fragments obtained in PCR were cloned into “T” vectors and transformed in competent cells DH10B line. After this, three samples of each fragment were sequenced from 5’ and 3’ extremities using a BigDye kit in an automatic sequencer. Sequences were edited in a consensus of each fragment and were submitted to BLAST-n / NCBI for similarity comparisions among other species. The sequence obtained with Z43D1 primers shows 938 bp enclosing exons 1 and 2 and intron 1. The primers E143F1 show 70 bp corresponding to exon 3 of bubaline SCD gene. Similarities were obtained between 85% and 97% among bubaline sequences and sequences of SCD gene described in human, mouse, rat, swine, bovine, caprine and ovine species. This study has permitted the identification and partial characterization of SCD codifing region in Bubalus bubalis specie.

  9. Broad substrate specificity of phosphotransbutyrylase from Listeria monocytogenes: A potential participant in an alternative pathway for provision of acyl CoA precursors for fatty acid biosynthesis.

    Sirobhushanam, Sirisha; Galva, Charitha; Sen, Suranjana; Wilkinson, Brian J; Gatto, Craig

    2016-09-01

    Listeria monocytogenes, the causative organism of the serious food-borne disease listeriosis, has a membrane abundant in branched-chain fatty acids (BCFAs). BCFAs are normally biosynthesized from branched-chain amino acids via the activity of branched chain α-keto acid dehydrogenase (Bkd), and disruption of this pathway results in reduced BCFA content in the membrane. Short branched-chain carboxylic acids (BCCAs) added as media supplements result in incorporation of BCFAs arising from the supplemented BCCAs in the membrane of L. monocytogenes bkd mutant MOR401. High concentrations of the supplements also effect similar changes in the membrane of the wild type organism with intact bkd. Such carboxylic acids clearly act as fatty acid precursors, and there must be an alternative pathway resulting in the formation of their CoA thioester derivatives. Candidates for this are the enzymes phosphotransbutyrylase (Ptb) and butyrate kinase (Buk), the products of the first two genes of the bkd operon. Ptb from L. monocytogenes exhibited broad substrate specificity, a strong preference for branched-chain substrates, a lack of activity with acetyl CoA and hexanoyl CoA, and strict chain length preference (C3-C5). Ptb catalysis involved ternary complex formation. Additionally, Ptb could utilize unnatural branched-chain substrates such as 2-ethylbutyryl CoA, albeit with lower efficiency, consistent with a potential involvement of this enzyme in the conversion of the carboxylic acid additives into CoA primers for BCFA biosynthesis. PMID:27320015

  10. Biotin augments acetyl CoA carboxylase 2 gene expression in the hypothalamus, leading to the suppression of food intake in mice.

    Sone, Hideyuki; Kamiyama, Shin; Higuchi, Mutsumi; Fujino, Kaho; Kubo, Shizuka; Miyazawa, Masami; Shirato, Saya; Hiroi, Yuka; Shiozawa, Kota

    2016-07-29

    It is known that biotin prevents the development of diabetes by increasing the functions of pancreatic beta-cells and improving insulin sensitivity in the periphery. However, its anti-obesity effects such as anorectic effects remain to be clarified. Acetyl CoA carboxylase (ACC), a biotin-dependent enzyme, has two isoforms (ACC1 and ACC2) and serves to catalyze the reaction of acetyl CoA to malonyl CoA. In the hypothalamus, ACC2 increases the production of malonyl CoA, which acts as a satiety signal. In this study, we investigated whether biotin increases the gene expression of ACC2 in the hypothalamus and suppresses food intake in mice administered excessive biotin. Food intake was significantly decreased by biotin, but plasma regulators of appetite, including glucose, ghrelin, and leptin, were not affected. On the other hand, biotin notably accumulated in the hypothalamus and enhanced ACC2 gene expression there, but it did not change the gene expression of ACC1, malonyl CoA decarboxylase (a malonyl CoA-degrading enzyme), and AMP-activated protein kinase α-2 (an ACC-inhibitory enzyme). These findings strongly suggest that biotin potentiates the suppression of appetite by upregulating ACC2 gene expression in the hypothalamus. This effect of biotin may contribute to the prevention of diabetes by biotin treatment. PMID:27181349

  11. Characterization of the JWST Pathfinder Mirror Dynamics Using the Center of Curvature Optical Assembly (CoCOA)

    Wells, Conrad; Hadaway, James B.; Olczak, Gene; Cosentino, Joseph; Johnston, John D.; Whitman, Tony; Connolly, Mark; Chaney, David; Knight, J. Scott; Telfer, Randal

    2016-01-01

    The JWST (James Webb Space Telescope) Optical Telescope Element (OTE) consists of a 6.6 meter clear aperture, 18-segment primary mirror, all-reflective, three-mirror anastigmat operating at cryogenic temperatures. To verify performance of the primary mirror, a full aperture center of curvature optical null test is performed under cryogenic conditions in Chamber A at NASA Johnson Space Center using an instantaneous phase measuring interferometer. After phasing the mirrors during the JWST Pathfinder testing, the interferometer is utilized to characterize the mirror relative piston and tilt dynamics under different facility configurations. The correlation between the motions seen on detectors at the focal plane and the interferometer validates the use of the interferometer for dynamic investigations. The success of planned test hardware improvements will be characterized by the multi-wavelength interferometer (MWIF) at the Center of Curvature Optical Assembly (CoCOA).

  12. The production of CO+(A 2Π) from dissociative ionization of CO2: a fragment ion-photon coincidence spectroscopic investigation

    Fragment ion-photon coincidence (FIPCO) spectra by 120 eV electron impact on carbon dioxide (CO2) have been observed, in which optical emission in the 250-600 nm region has been detected. There are a dominant CO2+ peak and a weak, broad CO+ peak in the FIPCO spectra. The kinetic energy distribution of CO+ correlated with the CO+(A 2Π-X 2Σ+) emission has been estimated on the basis of the Monte Carlo simulation of the CO+ band shape. This CO+(A 2Π) ion is produced through the dissociation process, CO2+e-→CO2+*[MET I 2Πu] + 2e-→CO+(A 2Π) + O(3P) + 2e-, where MET refers to multiple electron transitions. The production of CO+(B 2Σ+) is negligible compared with that of CO+(A 2Π). The produced CO+(A 2Π) ion is in vibrationally excited levels, and there is little population in the vibrational levels, v'≤3. (author)

  13. A guarda Nacional Republicana no combate à sinistralidade rodoviária, educação ou coação?

    Lopes, Fábio

    2012-01-01

    O presente Trabalho de Investigação Aplicada (TIA) com o tema “A GNR no Combate à Sinistralidade Rodoviária, Educação ou Coação?” tem como objetivo esclarecer o papel da Guarda Nacional Republicana (GNR) no combate à sinistralidade rodoviária, assim como clarificar esse papel no domínio da fiscalização/coação e da educação. No desenvolver do presente estudo foram formuladas hipóteses e questões de investigação subordinadas à questão central: “Qual ...

  14. Intracellular signal transduction of PBAN action in lepidopteran insects: inhibition of sex pheromone production by compactin, an HMG CoA reductase inhibitor.

    Ozawa, R; Matsumoto, S; Kim, G H; Uchiumi, K; Kurihara, M; Shono, T; Mitsui, T

    1995-06-27

    Pheromone biosynthesis activating neuropeptide (PBAN) regulates sex pheromone production in the pheromone glands of many species of female moths. In order to probe the biochemical steps as well as underlying mechanisms regulated by PBAN, we have tested the effect of chemicals on sex pheromone production by using an in vitro assay. Among the chemicals we tested here, compactin, a specific 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitor, clearly inhibited the pheromone biosynthesis in the silkworm, Bombyx mori, and the common cutworm, Spodoptera litura. Since the activation of HMG CoA reductase occurs by dephosphorylation mediated by a specific phosphatase and the biochemical step regulated by PBAN in bombykol biosynthesis is similar to the one catalyzed by HMG-CoA reductase in cholesterol biosynthesis, the present results support the idea that phosphoprotein phosphatase has a significant role to regulate bombykol production in the intracellular transduction of PBAN action in B. mori. PMID:7480881

  15. The prenyltransferase UBIAD1 is the target of geranylgeraniol in degradation of HMG CoA reductase.

    Schumacher, Marc M; Elsabrouty, Rania; Seemann, Joachim; Jo, Youngah; DeBose-Boyd, Russell A

    2015-01-01

    Schnyder corneal dystrophy (SCD) is an autosomal dominant disorder in humans characterized by abnormal accumulation of cholesterol in the cornea. SCD-associated mutations have been identified in the gene encoding UBIAD1, a prenyltransferase that synthesizes vitamin K2. Here, we show that sterols stimulate binding of UBIAD1 to the cholesterol biosynthetic enzyme HMG CoA reductase, which is subject to sterol-accelerated, endoplasmic reticulum (ER)-associated degradation augmented by the nonsterol isoprenoid geranylgeraniol through an unknown mechanism. Geranylgeraniol inhibits binding of UBIAD1 to reductase, allowing its degradation and promoting transport of UBIAD1 from the ER to the Golgi. CRISPR-CAS9-mediated knockout of UBIAD1 relieves the geranylgeraniol requirement for reductase degradation. SCD-associated mutations in UBIAD1 block its displacement from reductase in the presence of geranylgeraniol, thereby preventing degradation of reductase. The current results identify UBIAD1 as the elusive target of geranylgeraniol in reductase degradation, the inhibition of which may contribute to accumulation of cholesterol in SCD. PMID:25742604

  16. Feedback regulation of cholesterol synthesis:sterol-accelerated ubiquitination and degradation of HMG CoA reductase

    Russell A DeBose-Boyd

    2008-01-01

    3Hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase produces mevalonate,an important intermediate in the synthesis of cholesterol and essential nonsterol isoprenoids.The reductase is subject to an exorbitant amount of feedback control through multiple mechanisms that are mediated by sterol and nonsterol end-products of mevalonate metabolism.Here,Ⅰwill discuss recent advances that shed light on one mechanism for control of reductase,which involves rapid degradation of the enzyme.Accumulation of certain sterols triggers binding of reductase to endoplasmic reticulum (ER) membrane proteins called Insig-1 and Insig-2.Reductase-Insig binding results in recruitment of a membrane-associated ubiquitin ligase called gp78,which initiates ubiquitination of reductase.This ubiquitination is an obligatory reaction for recognition and degradation of reductase from ER membranes by cytosolic 26S proteasomes.Thus,sterol-accelerated degradation of reductase represents an example of how a general cellular process (ER-associated degradation) is used to control an important metabolic pathway (cholesterol synthesis).

  17. Impact of single-dose nandrolone decanoate on gonadotropins, blood lipids and HMG CoA reductase in healthy men.

    Gårevik, N; Börjesson, A; Choong, E; Ekström, L; Lehtihet, M

    2016-06-01

    The aim was to study the effect and time profile of a single dose of nandrolone decanoate (ND) on gonadotropins, blood lipids and HMG CoA reductase [3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCR)] in healthy men. Eleven healthy male participants aged 29-46 years were given a single dose of 150 mg ND as an intramuscular dose of Deca Durabol®, Organon. Blood samples for sex hormones, lipids and HMGCR mRNA analysis were collected prior to ND administration day 0, 4 and 14. A significant suppression of luteinising hormone (LH) and follicle-stimulating hormone (FSH) was seen after 4 days. Total testosterone and bioavailable testosterone level decreased significantly throughout the observed study period. A small but significant decrease in sexual hormone-binding globulin (SHBG) was seen after 4 days but not after 14 days. Total serum (S)-cholesterol and plasma (P)-apolipoprotein B (ApoB) increased significantly after 14 days. In 80% of the individuals, the HMGCR mRNA level was increased 4 days after the ND administration. Our results show that a single dose of 150 mg ND increases (1) HMGCR mRNA expression, (2) total S-cholesterol and (3) P-ApoB level. The long-term consequences on cardiovascular risk that may appear in users remain to be elucidated. PMID:26370185

  18. Inhibition of HMG CoA reductase reveals an unexpected role for cholesterol during PGC migration in the mouse

    Ewing Andrew G

    2008-12-01

    Full Text Available Abstract Background Primordial germ cells (PGCs are the embryonic precursors of the sperm and eggs. Environmental or genetic defects that alter PGC development can impair fertility or cause formation of germ cell tumors. Results We demonstrate a novel role for cholesterol during germ cell migration in mice. Cholesterol was measured in living tissue dissected from mouse embryos and was found to accumulate within the developing gonads as germ cells migrate to colonize these structures. Cholesterol synthesis was blocked in culture by inhibiting the activity of HMG CoA reductase (HMGCR resulting in germ cell survival and migration defects. These defects were rescued by co-addition of isoprenoids and cholesterol, but neither compound alone was sufficient. In contrast, loss of the last or penultimate enzyme in cholesterol biosynthesis did not alter PGC numbers or position in vivo. However embryos that lack these enzymes do not exhibit cholesterol defects at the stage at which PGCs are migrating. This demonstrates that during gestation, the cholesterol required for PGC migration can be supplied maternally. Conclusion In the mouse, cholesterol is required for PGC survival and motility. It may act cell-autonomously by regulating clustering of growth factor receptors within PGCs or non cell-autonomously by controlling release of growth factors required for PGC guidance and survival.

  19. Study on the 3-hydroxy-3-methyl-glutaryl CoA reductase inhibitory properties of Agaricus bisporus and extraction of bioactive fractions using pressurised solvent technologies

    Gil-Ramírez, Alicia; Clavijo, Cristina; Palanisamy, Marimuthu; Ruiz-Rodríguez, Alejandro; Navarro-Rubio, María; Pérez, Margarita; Marin, Francisco R.; Reglero, Guillermo; Soler-Rivas, Cristina

    2013-01-01

    [Background]: Agaricus bisporus mushrooms were able to lower cholesterol levels in hypercholesterolaemic rats and it was suggested that dietary fibre might inhibit cholesterol absorption. However, A. bisporus extracts were also able to inhibit the 3-hydroxy-3-methyl-glutaryl CoA reductase (HMGCR, the key enzyme in the cholesterol biosynthetic pathway) and this might also contribute to the observed lowering of cholesterol levels in serum. [Results]: The methanol-water extracts obtained from A....

  20. Studies of Human 2,4-Dienoyl CoA Reductase Shed New Light on Peroxisomal β-Oxidation of Unsaturated Fatty Acids

    Hua, Tian; Wu, Dong; Ding, Wei; Wang, Jiangyun; Shaw, Neil; Liu, Zhi-Jie [Nankai; (Chinese Aca. Sci.)

    2012-10-15

    Peroxisomes play an essential role in maintaining fatty acid homeostasis. Although mitochondria are also known to participate in the catabolism of fatty acids via β-oxidation, differences exist between the peroxisomal and mitochondrial β-oxidation. Only peroxisomes, but not mitochondrion, can shorten very long chain fatty acids. Here, we describe the crystal structure of a ternary complex of peroxisomal 2,4-dienoyl CoA reductases (pDCR) with hexadienoyl CoA and NADP, as a prototype for comparison with the mitochondrial 2,4-dienoyl CoA reductase (mDCR) to shed light on the differences between the enzymes from the two organelles at the molecular level. Unexpectedly, the structure of pDCR refined to 1.84 Å resolution reveals the absence of the tyrosine-serine pair seen in the active site of mDCR, which together with a lysine and an asparagine have been deemed a hallmark of the SDR family of enzymes. Instead, aspartate hydrogen-bonded to the Cα hydroxyl via a water molecule seems to perturb the water molecule for protonation of the substrate. Our studies provide the first structural evidence for participation of water in the DCR-catalyzed reactions. Biochemical studies and structural analysis suggest that pDCRs can catalyze the shortening of six-carbon-long substrates in vitro. However, the Km values of pDCR for short chain acyl CoAs are at least 6-fold higher than those for substrates with 10 or more aliphatic carbons. Unlike mDCR, hinge movements permit pDCR to process very long chain polyunsaturated fatty acids.

  1. Purification, molecular cloning, and expression of 2-hydroxyphytanoyl- CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during à-oxidation of 3- methyl-branched fatty acids

    Foulon, V; Croes, K; Waelkens, E

    1999-01-01

    Purification, molecular cloning, and expression of 2-hydroxyphytanoyl- CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during à-oxidation of 3- methyl-branched fatty acids

  2. [The protective effect of pantothenic acid derivatives and changes in the system of acetyl CoA metabolism in acute ethanol poisoning].

    Moiseenok, A G; Dorofeev, B F; Omel'ianchik, S N

    1988-01-01

    Calcium pantothenate (CaP), calcium 4'-phosphopantothenate (CaPP), pantethine, panthenol, sulfopantetheine and CoA decrease acute toxicity of acetaldehyde in mice. All studied compounds diminish duration of the narcotic action of ethanol--ET (3.5 g/kg intraperitoneally) in mice and rats. In the latter this effect is realized at the expense of "long sleeping" and "middle sleeping" animals. CaP (150 mg/kg subcutaneously) and CaPP (100 mg/kg subcutaneously) prevent hypothermia and a decrease of oxygen consumption in rats induced by ET administration. Combined administration of ET, CaP and CaPP leads to a characteristic increase of acid-soluble CoA fractions in the rat liver and a relative decrease of acetyl CoA synthetase and N-acetyltransferase reactions. The antitoxic effect of preparations of pantothenic acid is not mediated by CoA-dependent reactions of detoxication, but most probably is due to intensification of ET oxidation and perhaps to its elimination from the organism. PMID:2905277

  3. Mutation analysis of methylmalonyl CoA mutase gene exon 2 in Egyptian families: Identification of 25 novel allelic variants

    Dina A. Ghoraba

    2015-02-01

    Full Text Available Methylmalonic aciduria (MMA is an autosomal recessive disorder of methylmalonate and cobalamin (cbl; vitamin B12 metabolism. It is an inborn error of organic acid metabolism which commonly results from a defect in the gene encoding the methylmalonyl-CoA mutase (MCM apoenzyme. Here we report the results of mutation study of exon 2 of the methylmalonyl CoA mutase (MUT gene, coding MCM residues from 1 to 128, in ten unrelated Egyptian families affected with methylmalonic aciduria. Patients were presented with a wide-anion gap metabolic acidosis. The diagnosis has established by the measurement of C3 (propionylcarnitine and C3:C2 (propionylcarnitine/acetylcarnitine in blood by using liquid chromatography–tandem mass spectrometry (LC/MS–MS and was confirmed by the detection of an abnormally elevated level of methylmalonic acid in urine by using gas chromatography–mass spectrometry (GC/MS and isocratic cation exchange high-performance liquid-chromatography (HPLC. Direct sequencing of gDNA of the MUT gene exon 2 has revealed a total of 26 allelic variants: ten of which were intronic, eight were located upstream to the exon 2 coding region, four were novel modifications predicted to affect the splicing region, three were novel mutations within the coding region: c.15G>A (p.K5K, c.165C>A (p.N55K and c.7del (p.R3EfsX14, as well as the previously reported mutation c.323G>A (p.R108H.

  4. 1200 nt rat liver mRNA identified by differential hybridization exhibits coordinate regulation with 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase

    Differential hybridization has been used to identify genes in rat liver that encode transcripts which are increased by the drugs cholestyramine and mevinolin and are decreased by dietary cholesterol. This approach should prove useful in isolating and identifying coordinately regulated genes involved in the isoprene biosynthetic pathway. Rat liver poly (A)+ RNA was isolated from animals fed diets supplemented with either cholestyramine and mevinolin or with cholesterol. Radiolabeled cDNAs generated from these two RNA preparations were used to screen a rat cDNAs library. A preliminary screen of 10,000 recombinants has led to the identification of a clone with an insert of 1200 bp that hybridizes to a mRNA species of about 1200 nt. The level of this RNA species in rat liver is elevated by the drugs cholestyramine and mevinolin and is decreased by cholesterol feeding. This RNA species is also decreased by mevalonate administration to rats. The regulation of this 1200 nt mRNA species mirrors that of HMG CoA reductase and HMG CoA synthase. It seems very likely that this 1200 nt mRNA encodes a polypeptide which is involved in the isoprene biosynthetic pathway

  5. Synthesis of O-[11C]acetyl CoA, O-[11C]acetyl-L-carnitine, and L-[11C]carnitine labelled in specific positions, applied in PET studies on rhesus monkey

    The syntheses of L-carnitine, O-acetyl CoA, and O-acetyl-L-carnitine labelled with 11C at the 1- or 2-position of the acetyl group or the N-methyl position of carnitine, using the enzymes acetyl CoA synthetase and carnitine acetyltransferase, are described. With a total synthesis time of 45 min, O-[1-11C]acetyl CoA and O-[2-11C]acetyl CoA was obtained in 60-70% decay-corrected radiochemical yield, and O-[1-11C]acetyl-L-carnitine and O-[2-11C]acetyl-L-carnitine in 70-80% yield, based on [1-11C]acetate or [2-11C]acetate, respectively. By an N-methylation reaction with [11C]methyl iodide, L-[methyl-11C]carnitine was obtained within 30 min, and O-acetyl-L-[methyl-11C]carnitine within 40 min, giving a decay-corrected radiochemical yield of 60% and 40-50%, respectively, based on [11C]methyl iodide. Initial data of the kinetics of the different 11C-labelled L-carnitine and acetyl-L-carnitines in renal cortex of anaesthetized monkey (Macaca mulatta) are presented

  6. Synthesis of O-[{sup 11}C]acetyl CoA, O-[{sup 11}C]acetyl-L-carnitine, and L-[{sup 11}C]carnitine labelled in specific positions, applied in PET studies on rhesus monkey

    Jacobson, Gunilla B.; Watanabe, Yasuyoshi; Valind, Sven; Kuratsune, Hirohiko; Laangstroem, Bengt

    1997-07-01

    The syntheses of L-carnitine, O-acetyl CoA, and O-acetyl-L-carnitine labelled with {sup 11}C at the 1- or 2-position of the acetyl group or the N-methyl position of carnitine, using the enzymes acetyl CoA synthetase and carnitine acetyltransferase, are described. With a total synthesis time of 45 min, O-[1-{sup 11}C]acetyl CoA and O-[2-{sup 11}C]acetyl CoA was obtained in 60-70% decay-corrected radiochemical yield, and O-[1-{sup 11}C]acetyl-L-carnitine and O-[2-{sup 11}C]acetyl-L-carnitine in 70-80% yield, based on [1-{sup 11}C]acetate or [2-{sup 11}C]acetate, respectively. By an N-methylation reaction with [{sup 11}C]methyl iodide, L-[methyl-{sup 11}C]carnitine was obtained within 30 min, and O-acetyl-L-[methyl-{sup 11}C]carnitine within 40 min, giving a decay-corrected radiochemical yield of 60% and 40-50%, respectively, based on [{sup 11}C]methyl iodide. Initial data of the kinetics of the different {sup 11}C-labelled L-carnitine and acetyl-L-carnitines in renal cortex of anaesthetized monkey (Macaca mulatta) are presented.

  7. A propionate CoA-transferase of Ralstonia eutropha H16 with broad substrate specificity catalyzing the CoA thioester formation of various carboxylic acids.

    Lindenkamp, Nicole; Schürmann, Marc; Steinbüchel, Alexander

    2013-09-01

    In this study, we have investigated a propionate CoA-transferase (Pct) homologue encoded in the genome of Ralstonia eutropha H16. The corresponding gene has been cloned into the vector pET-19b to yield a histidine-tagged enzyme which was expressed in Escherichia coli BL21 (DE3). After purification, high-performance liquid chromatography/mass spectrometry (HPLC/MS) analyses revealed that the enzyme exhibits a broad substrate specificity for carboxylic acids. The formation of the corresponding CoA-thioesters of acetate using propionyl-CoA as CoA donor, and of propionate, butyrate, 3-hydroxybutyrate, 3-hydroxypropionate, crotonate, acrylate, lactate, succinate and 4-hydroxybutyrate using acetyl-CoA as CoA donor could be shown. According to the substrate specificity, the enzyme can be allocated in the family I of CoA-transferases. The apparent molecular masses as determined by gel filtration and detected by SDS polyacrylamide gel electrophoresis were 228 and 64 kDa, respectively, and point to a quaternary structure of the native enzyme (α4). The enzyme exhibited similarities in sequence and structure to the well investigated Pct of Clostridium propionicum. It does not contain the typical conserved (S)ENG motif, but the derived motif sequence EXG with glutamate 342 to be, most likely, the catalytic residue. Due to the homo-oligomeric structure and the sequence differences with the subclasses IA-C of family I CoA-transferases, a fourth subclass of family I is proposed, comprising - amongst others - the Pcts of R. eutropha H16 and C. propionicum. A markerless precise-deletion mutant R. eutropha H16∆pct was generated. The growth and accumulation behaviour of this mutant on gluconate, gluconate plus 3,3'-dithiodipropionic acid (DTDP), acetate and propionate was investigated but resulted in no observable phenotype. Both, the wild type and the mutant showed the same growth and storage behaviour with these carbon sources. It is probable that R. eutropha H16 is upregulating

  8. Effect of various eicosanoid products of arachidonic acid on the acyl CoA: Cholesterol acyl transferase activity in three different mammalian cell lines

    Acylcoenzyme A:cholesterol acyltransferase (ACAT) catalyzes cholesterol ester synthesis intracellularly and has been implicated in the development of atherosclerosis. An in vitro assay has been adapted for determining ACAT activity from rat FU5AH hepatoma, Chinese hamster ovary (CHO) and rat thoracic aortic smooth muscle (RSM) cells. Formation of 14C-labelled cholesteryl oleate at 0 to 60 min ± cholesterol was determined; in the presence of exogenous cholesterol, ACAT activity was approximately linear and surpassed the plateau observed in ACAT activity without cholesterol. Increasing exogenous cholesterol concentration, the amount of oleoyl CoA or the amount of microsomal protein produced a corresponding increase in ACAT activity, while ester formation was slightly increased by decreasing the ratio of Triton WR-1339 to cholesterol. Both the thromboxane A2 (TxA2) mimic, U-44069, and the inflammatory lipoxygenase product, LTB4, decreased optimal in vitro microsomal ACAT activity from RSM, but not form FU5AH, while CHO ACAT activity was suppressed by LTBr only. PGI2, PGE2 and PGF2α had minimal effects for each cell type

  9. Molecular cloning and characterization of Polygalacturonase-Inhibiting Protein and Cinnamoyl-Coa Reductase genes and their association with fruit storage conditions in blueberry (Vaccinium corymbosum)

    Khraiwesh, Basel

    2013-05-13

    Blueberry is a widely grown and easily perishable fruit crop. An efficient post-harvest handling is critical, and for that purpose gene technology methods have been part of ongoing programmes to improve crops with high food values such as blueberry. Here we report the isolation, cloning, characterization and differential expression levels of two cDNAs encoding Polygalacturonase-Inhibitor Protein (PGIP) and Cinnamoyl-Coa Reductase (CCR) from blueberry fruits in relation to various storage conditions. The open reading frame of PGIP and CCR encodes a polypeptide of 329 and 347 amino acids, respectively. To assess changes in the expression of blueberry PGIP and CCR after harvest, a storage trial was initiated. The northern blots hybridization showed a clear differential expression level of PGIP and CCR between freshly harvested and stored fruits as well as between fruits stored under various storage conditions. Although the prospects of exploiting such a strategy for crop improvement are limited, the results provide further insight into the control of the quality over the storage period at the molecular level.

  10. Sudden unexpected infant death (SUDI in a newborn due to medium chain acyl CoA dehydrogenase (MCAD deficiency with an unusual severe genotype

    Lovera Cristina

    2012-10-01

    Full Text Available Abstract Medium chain acyl CoA dehydrogenase deficiency (MCAD is the most common inborn error of fatty acid oxidation. This condition may lead to cellular energy shortage and cause severe clinical events such as hypoketotic hypoglycemia, Reye syndrome and sudden death. MCAD deficiency usually presents around three to six months of life, following catabolic stress as intercurrent infections or prolonged fasting, whilst neonatal-onset of the disease is quite rare. We report the case of an apparently healthy newborn who suddenly died at the third day of life, in which the diagnosis of MCAD deficiency was possible through peri-mortem blood-spot acylcarnitine analysis that showed very high concentrations of octanoylcarnitine. Genetic analysis at the ACADM locus confirmed the biochemical findings by demonstrating the presence in homozygosity of the frame-shift c.244dup1 (p.Trp82LeufsX23 mutation, a severe genotype that may explain the unusual and very early fatal outcome in this newborn. This report confirms that inborn errors of fatty acid oxidation represent one of the genetic causes of sudden unexpected deaths in infancy (SUDI and underlines the importance to include systematically specific metabolic screening in any neonatal unexpected death.

  11. 3-Hydroxy-3-methylglutaryl CoA lyase (HL): Mouse and human HL gene (HMGCL) cloning and detection of large gene deletions in two unrelated HL-deficient patients

    Wang, S.P.; Robert, M.F.; Mitchell, G.A. [Hopital Sainte-Justine, Quebec (Canada)] [and others

    1996-04-01

    3-hydroxy-3-methylglutaryl CoA lyase (HL, EC 4.1.3.4) catalyzes the cleavage of 3-hydroxy-3-methylglutaryl CoA to acetoacetic acid and acetyl CoA, the final reaction of both ketogenesis and leucine catabolism. Autosomal-recessive HL deficiency in humans results in episodes of hypoketotic hypoglycemia and coma. Using a mouse HL cDNA as a probe, we isolated a clone containing the full-length mouse HL gene that spans about 15 kb of mouse chromosome 4 and contains nine exons. The promoter region of the mouse HL gene contains elements characteristic of a housekeeping gene: a CpG island containing multiple Sp1 binding sites surrounds exon 1, and neither a TATA nor a CAAT box are present. We identified multiple transcription start sites in the mouse HL gene, 35 to 9 bases upstream of the translation start codon. We also isolated two human HL genomic clones that include HL exons 2 to 9 within 18 kb. The mouse and human HL genes (HGMW-approved symbol HMGCL) are highly homologous, with identical locations of intron-exon junctions. By genomic Southern blot analysis and exonic PCR, was found 2 of 33 HL-deficient probands to be homozygous for large deletions in the HL gene. 26 refs., 4 figs., 2 tabs.

  12. GenBank blastx search result: AK061948 [KOME

    Full Text Available AK061948 001-042-E07 U17226.1 Sinorhizobium meliloti carbon flux regulator (aniA), beta-ketothiolase (phb...A), and acetoacetyl CoA reductase (phbB) genes, complete cds.|BCT BCT 1e-54 +3 ...

  13. GenBank blastx search result: AK059654 [KOME

    Full Text Available AK059654 001-031-C10 U17226.1 Sinorhizobium meliloti carbon flux regulator (aniA), beta-ketothiolase (phb...A), and acetoacetyl CoA reductase (phbB) genes, complete cds.|BCT BCT 2e-69 +1 ...

  14. Walnut oil increases cholesterol efflux through inhibition of stearoyl CoA desaturase 1 in THP-1 macrophage-derived foam cells

    Gillies Peter J

    2011-08-01

    Full Text Available Abstract Background Walnuts significantly decrease total and low-density lipoprotein cholesterol in normo- and hypercholesterolemic individuals. No study to date has evaluated the effects of walnuts on cholesterol efflux, the initial step in reverse cholesterol transport, in macrophage-derived foam cells (MDFC. The present study was conducted to investigate the mechanisms by which walnut oil affects cholesterol efflux. Methods The extract of English walnuts (walnut oil was dissolved in DMSO and applied to cultured THP-1 MDFC cells (0.5 mg/mL. THP-1 MDFC also were treated with human sera (10%, v:v taken from subjects in a walnut feeding study. Cholesterol efflux was examined by liquid scintillation counting. Changes in gene expression were quantified by real time PCR. Results Walnut oil treatment significantly increased cholesterol efflux through decreasing the expression of the lipogenic enzyme stearoyl CoA desaturase 1 (SCD1 in MDFC. Alpha-linolenic acid (ALA, the major n-3 polyunsaturated fatty acids found in walnuts, recaptured SCD1 reduction in MDFC, a mechanism mediated through activation of nuclear receptor farnesoid-X-receptor (FXR. Postprandial serum treatment also increased cholesterol efflux in MDFC. When categorized by baseline C-reactive protein (CRP; cut point of 2 mg/L, subjects in the lower CRP sub-group benefited more from dietary intervention, including a more increase in cholesterol efflux, a greater reduction in SCD1, and a blunted postprandial lipemia. Conclusion In conclusion, walnut oil contains bioactive molecules that significantly improve cholesterol efflux in MDFC. However, the beneficial effects of walnut intake may be reduced by the presence of a pro-inflammatory state. Trial Registration ClinicalTrials.gov: NCT00938340

  15. Human mitochondrial HMG CoA synthase: Liver cDNA and partial genomic cloning, chromosome mapping to 1p12-p13, and possible role in vertebrate evolution

    Boukaftane, Y.; Robert, M.F.; Mitchell, G.A. [Hopital Sainte-Justine, Montreal (Canada)] [and others

    1994-10-01

    Mitochondrial 3-hydroxy-3-methylglutaryl CoA synthase (mHS) is the first enzyme of ketogenesis, whereas the cytoplasmic HS isozyme (cHS) mediates an early step in cholersterol synthesis. We here report the sequence of human and mouse liver mHS cDNAs, the sequence of an HS-like cDNA from Caenorhabditis elegans, the structure of a partial human mHS genomic clone, and the mapping of the human mHS gene to chromosome 1p12-p13. the nucleotide sequence of the human mHS cDNA encodes a mature mHS peptide of 471 residues, with a mean amino acid identity of 66.5% with cHS from mammals and chicken. Comparative analysis of all known mHS and cHS protein and DNA sequences shows a high degree of conservation near the N-terminus that decreases progressively toward the C-terminus and suggests that the two isozymes arose from a common ancestor gene 400-900 million years ago. Comparison of the gene structure of mHS and cHS is also consistant with a recent duplication event. We hypothesize that the physiologic result of the HS gene duplication was the appearance of HS within the mitochondria around the time of emergence of early vertebrates, which linked preexisting pathways of beta oxidation and leucine catabolism and created the HMG CoA pathway of ketogenesis, thus providing a lipid-derived energy source for the vertebrate brain. 56 refs., 4 figs., 2 tabs.

  16. Pesquisa do antígeno circulante de Cryptococcus neoformans em líquido cefalorraqueano pelo teste de coaglutinação Coaglutination test (COA for Cryptococcus neoformans circulating antigen detection in cerebral spinal fluid (CSF

    Maria Isabel Nogueira Cano

    1990-12-01

    Full Text Available Foram utilizadas 82 LCR de transplantados renais (24 pacientes, 43 LCR de pacientes com críptococose comprovada (controles positivos, 35 LCR de pacientes com outras doenças (histoplasmose, paracoccidioidomicose e infecções bacterianas como controles negativos. Os primeiros foram cultivados em ágar Sabouraud com sementes de girassol e juntamente com os demais examinado pelo teste de látex para pesquisa de antígeno circulante de C. neoformans, qualitativamente. O teste de Coaglutinação foi realizado qualitativamente e quantitativamente, encontrando-se títulos até a diluição 1:2048. Não foram detectadas reações falso-positivas ou falso-negativas entre os controles. Como prova de valor diagnóstico demonstrou: sensibilidade - 92,1%; especificidade - 92,6% e eficiência - 92,3%. Provou também ser um teste rápido, exato e econômico, embora sua escolha dependa do pré-tratamento de LCR (80ºC por 3 a 5 minutos e soros (diluição ou álcali-precipitação para evitar autoaglutinação e aumentar a sensibilidade da reação.We tested 82 CSF of 24 renal transplanted patients (RT with cerebral cryptococcosis, 8 CSF of asymptomatic RT patients, 43 CSF of proven cryptococcosis cases (positive control and 35 CSF of patients with other diseases (histoplasmosis, paracoccidioidomycosis and bacterial infections as negative control. The RT CSF were cultured in Sabouraud agar slant added with sunflower seeds and both control and RT CSF were qualitatively examined by cryptococcosis latex test (Crypto-LA test. The COA test was developed both qualitatively and quantitatively. The highest titre encountered was 1:2048. No false reactions appeared among the controls. The diagnostic value demonstrated by Galen and Gambino's method was: sensitivity - 92.1%; specificity - 92.6% and efficiency - 92.3%. Besides that, the COA proved to be quick, exact and cheap, but it depends on CSF and sera pre-treatment, in order to avoid autoagglutination and increase

  17. The effect of charge reversal mutations in the alpha-helical region of liver fatty acid binding protein on the binding of fatty-acyl CoAs, lysophospholipids and bile acids.

    Hagan, Robert M; Davies, Joanna K; Wilton, David C

    2002-10-01

    Liver fatty acid binding protein (LFABP) is unique among the various types of FABPs in that it can bind a variety of ligands in addition to fatty acids. LFABP is able to bind long chain fatty acids with a 2:1 stoichiometry and the crystal structure has identified two fatty acid binding sites in the binding cavity. The presumed primary site (site 1) involves the fatty acid binding with the carboxylate group buried in the cavity whereas the fatty acid at site 2 has the carboxylate group solvent-exposed within the ligand portal region and in the vicinity of alpha-helix II. The alpha-helical region contains three cationic residues, K20, K31, K33 and modelling studies suggest that K31 on alpha-helix II could make an electrostatic contribution to anionic ligands binding to site 2. The preparation of three charge reversal mutants of LFABP, K20E, K31E and K33E has allowed an investigation of the role of site 2 in ligand binding, particularly those ligands with a bulky anionic head group. The binding of oleoyl CoA, lysophosphatidic acid, lysophosphatidylcholine, lithocholic acid and taurolithocholate 3-sulphate to LFABP has been studied using the alpha-helical mutants. The results support the concept that such ligands bind at site 2 of LFABP where solvent exposure allows the accommodation of their bulky anionic group. PMID:12479568

  18. 尾叶桉GLU4肉桂酰-辅酶A还原酶基因克隆及原核表达%Cloning and prokaryotic expression of cinnamoyl Co-A reductase of Eucalyptus urophylla clone GLU4

    陈博雯; 盖颖; 蒋湘宁

    2014-01-01

    肉桂酰-辅酶A还原酶(Cinnamoyl Co-A Reductase,CCR)是木质素合成中的关键酶,根据植物中CCR保守序列设计引物,以尾叶桉GLU4嫩茎为材料克隆到其CCR基因,命名为EuCCR。该基因gDNA长2918 bp,cDNA长1045 bp,CDS区编码336个氨基酸。EuCCR核酸序列与GenBank已登录的桉属植物CCR基因同源性达到96%以上,与伞房属、杯果木属植物CCR的同源性达85%以上,其编码的氨基酸序列经比对发现具有完整FR_SDR_e结构域及NADP结合位点和底物结合位点,与可可树等植物中CCR基因编码序列同源性也在84%以上,确定为CCR基因。对EuCCR蛋白序列理化性质及结构进行生物信息学分析,利用MEGA软件对基因序列进行系统进化树分析。采用pQE30/M15系统对EuCCR进行原核表达,重组质粒成功表达分子量约36 kD的目的蛋白。本研究从尾叶桉GLU4中克隆得到EuCCR基因并原核表达,为该基因的酶学分析以及利用该基因转化调控尾叶桉木质素合成奠定基础。%Cinnamoyl Co-A reductase is a key enzyme in lignin synthesis pathway. A CCR gene was cloned from the immature stem of Eucalyptus urophylla clone GLU4 and named EuCCR by using speciifc primers based on the highly conserved sequences of plant CCR. The gDNA and cDNA sequence of EuCCR were 2918 bp and 1045 bp respectively, which CDS encodes 336 amino acid residues. EuCCR had more than 96%sequence homology with Eucalyptus that had been logged in GenBank, and its homology with Angophora and Corymbia were over 85%. EuCCR encoding sequence was analyzed, the result shows it has an entire FR_SDR_e domain, a NADP binding site and a substrate binding site. The homology with Theobroma cacao and others were over 84%. The physicochemical property, structure of EuCCR and its phylogenetic analysis were analyzed by using bioinformatics tools and MEGA. The SDS-PAGE analysis showed that EuCCR was transformed into pQE30/M15 system and fusion protein with

  19. Role of acetyl CoA

    Existence of an acetyltransferase, which catalizes acetylation of deacetylcephalosporin C to cephalosporin C, was demonstrated for the first time in cell-free extracts of Cephalosporium acremonium. The pH optimum of the enzyme appeared to be 7.0 to 7.5 and the enzyme required essentially Mg2+ as a cofactor for its reaction. The activity of this enzyme was not observed in the cell-free extracts of deacetylcephalosporin C-producing mutants Nos. 20, 29, 36 and 40, but was recovered in a revertant obtained from the mutant No. 40. These results indicate that deacetylcephalosporin C accumulation by these mutants was due to the lack of the acetyltransferase and made it reasonable that the terminal reaction of cephalosporin C biosynthesis in Cephalosporium acremonium proceeded by the catalytic action of acetyltransferase. (auth.)

  20. Main: 1COA [RPSD[Archive

    Full Text Available hymotrypsin Inhibitor 2 Biochemistry V. 32 11259 1993 EMBL; X05404; CAA28988.1; -.|PIR; A01292; EIBH2A.|PDB;..., A.R.Fersht The Effect Of Cavity Creating Mutations In The Hydrophobic Core Of C

  1. COA User's Guide

    Fox, B.; Pautz, J.; Sellers, C.

    1999-01-28

    The Department of Energy (DOE) has one of the largest and most complete collections of information on crude oil composition that is available to the public. The computer program that manages this database of crude oil analyses has recently been rewritten to allow easier access to this information. This report describes how the new system can be accessed and how the information contained in the Crude Oil Analysis Data Bank can be obtained.

  2. Regulation of Isoprenoid Pheromone Biosynthesis in Bumblebee Males.

    Prchalová, Darina; Buček, Aleš; Brabcová, Jana; Žáček, Petr; Kindl, Jiří; Valterová, Irena; Pichová, Iva

    2016-02-01

    Males of the closely related species Bombus terrestris and Bombus lucorum attract conspecific females by completely different marking pheromones. MP of B. terrestris and B. lucorum pheromones contain mainly isoprenoid (ISP) compounds and fatty acid derivatives, respectively. Here, we studied the regulation of ISP biosynthesis in both bumblebees. RNA-seq and qRT-PCR analyses indicated that acetoacetyl-CoA thiolase (AACT), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), and farnesyl diphosphate synthase (FPPS) transcripts are abundant in the B. terrestris labial gland. Maximal abundance of these transcripts correlated well with AACT enzymatic activity detected in the LG extracts. In contrast, transcript abundances of AACT, HMGR, and FPPS in B. lucorum were low, and AACT activity was not detected in LGs. These results suggest that transcriptional regulation plays a key role in the control of ISP biosynthetic gene expression and ISP pheromone biosynthesis in bumblebee males. PMID:26632352

  3. Metabolic Engineering of Escherichia coli for Enhanced Production of (R)- and (S)-3-Hydroxybutyrate▿

    Tseng, Hsien-chung; Martin, Collin H.; David R. Nielsen; Prather, Kristala L. Jones

    2009-01-01

    Synthetic metabolic pathways have been constructed for the production of enantiopure (R)- and (S)-3-hydroxybutyrate (3HB) from glucose in recombinant Escherichia coli strains. To promote maximal activity, we profiled three thiolase homologs (BktB, Thl, and PhaA) and two coenzyme A (CoA) removal mechanisms (Ptb-Buk and TesB). Two enantioselective 3HB-CoA dehydrogenases, PhaB, producing the (R)-enantiomer, and Hbd, producing the (S)-enantiomer, were utilized to control the 3HB chirality across ...

  4. 应用聚合酶链式反应快速特异鉴定假单胞菌和伯克霍尔德氏菌(R)-3-羟基酯酰载酯蛋白-辅酶A转酰基酶基因%Specific Identification of ( R )-3-hydroxyacyl-ACP: CoA Transacylase Gene from Pseudomonas and Burkholderia Strains by Polymerase Chain Reaction

    郑重; 陈金春; 田鸿磊; 贝锋锋; 陈国强

    2005-01-01

    聚羟基脂肪酸酯(PHA)是一类具有广泛应用前景的可降解生物塑料.因其可以以葡萄糖等廉价底物直接发酵生产PHA而日益受到重视.目前的研究表明在积累中长链PHA的假单胞菌中,由phaG基因编码的(R)-3-羟基酯酰载酯蛋白-辅酶A转酰基酶(PhaG)起关键作用,但目前为止对该蛋白还知之甚少.通过聚合酶链式反应(PCR)建立了一种快速、特异鉴定phaG基因的方法,应用该方法成功地从两株积累不同PHA的假单胞菌Pseudomonas stutzeri 1317和Pseudomonas nitroreducens0802中分别克隆得到phaG基因,并在phaG基因突变株Pseudomonasputida PHAGN-21中表达成功.同时,还首次报道了从非假单胞菌菌株Burkholderia caryophylli AS 1.2741中鉴定得到phaG基因,提示PhaG介导的中长链PHA合成途径作为一种通用的代谢模式在细菌中广泛存在,为进一步实现从廉价的非相关底物合成中长链PHA提供了必要的分子生物学基础.%Polyhydroxyalkanoates (PHA) were biodegradable thermoplastics. Due to their broad applications, direct biosynthesis of PHA from inexpensive substrates, such as carbohydrates, is actively pursued. It has been recently revealed that (R)-3-hydroxyacyl-ACP: CoA transacylase (PhaG) played an important role in this pathway. In this study, a polymerase chain reaction(PCR) protocol was developed for the rapid and specific identification of phaG gene from various bacteria. Using the PCR strategy, the complete open reading frames of two phaG genes from Pseudomonas stutzeri 1317 and Pseudomonas nitroreducens 0802were cloned from the genomic DNA and functionally expressed in Pseudomonas putida PHAGN-21. Furthermore, this strategy was successful applied in non-Pseudomonas strains, such as Burkholderia. These results suggest that PhaG-mediated pathway of medium-chain-length polyhydroxyalkanoates was widespread among bacteria.

  5. Isotopomer Spectral Analysis: Utilizing Nonlinear Models in Isotopic Flux Studies.

    Kelleher, Joanne K; Nickol, Gary B

    2015-01-01

    We present the principles underlying the isotopomer spectral analysis (ISA) method for evaluating biosynthesis using stable isotopes. ISA addresses a classic conundrum encountered in the use of radioisotopes to estimate biosynthesis rates whereby the information available is insufficient to estimate biosynthesis. ISA overcomes this difficulty capitalizing on the additional information available from the mass isotopomer labeling profile of a polymer. ISA utilizes nonlinear regression to estimate the two unknown parameters of the model. A key parameter estimated by ISA represents the fractional contribution of the tracer to the precursor pool for the biosynthesis, D. By estimating D in cells synthesizing lipids, ISA quantifies the relative importance of two distinct pathways for flux of glutamine to lipid, reductive carboxylation, and glutaminolysis. ISA can also evaluate the competition between different metabolites, such as glucose and acetoacetate, as precursors for lipogenesis and thereby reveal regulatory properties of the biosynthesis pathway. The model is flexible and may be expanded to quantify sterol biosynthesis allowing tracer to enter the pathway at three different positions, acetyl CoA, acetoacetyl CoA, and mevalonate. The nonlinear properties of ISA provide a method of testing for the presence of gradients of precursor enrichment illustrated by in vivo sterol synthesis. A second ISA parameter provides the fraction of the polymer that is newly synthesized over the time course of the experiment. In summary, ISA is a flexible framework for developing models of polymerization biosynthesis providing insight into pools and pathway that are not easily quantified by other techniques. PMID:26358909

  6. Treatment with the 3-Ketoacyl-CoA Thiolase Inhibitor Trimetazidine Does Not Exacerbate Whole-Body Insulin Resistance in Obese Mice

    Ussher, John R.; Keung, Wendy; Fillmore, Natasha; Koves, Timothy R.; Mori, Jun; Zhang, Liyan; Lopaschuk, David G.; Ilkayeva, Olga R.; Wagg, Cory S.; Jaswal, Jagdip S.; Muoio, Deborah M.; Lopaschuk, Gary D.

    2014-01-01

    There is a growing need to understand the underlying mechanisms involved in the progression of cardiovascular disease during obesity and diabetes. Although inhibition of fatty acid oxidation has been proposed as a novel approach to treat ischemic heart disease and heart failure, reduced muscle fatty acid oxidation rates may contribute to the development of obesity-associated insulin resistance. Our aim was to determine whether treatment with the antianginal agent trimetazidine, which inhibits...

  7. Earthquake swarm associated with volcanic eruption, CuraCoa Reef Area, Northern Tonga, July 1973

    G. K. SUTTON

    1974-06-01

    Full Text Available A submarine volcanic eruption near Curagoa Reef, first observed on 12 J u l y 1973 (U.T. f r om Tafalii Island, northern Tonga, was associated with an e a r t h q u a k e swarm in t h e same area. The swarm began about 03'1 on I I J u l y and died away gradually about 07'' on 13 J u l y , ft comprised 504 events of magnitude Mi, „2= 3.4, the largest being of magnitude Ml = 5.1. The swarm area for these comparatively low magnitude earthquakes was abnormally large The v a r i a t i o n in r a t e of e a r t h q u a k e occurrence during t h e s w a rm shows two distinct stages, one similar to t h a t in a foresliock sequence, and t h e other like t h a t in a n a f t e r s h o c k sequence, with t h e largest events occurring between t h e two. The average value of b, defining t h e f r e q u e n c y - m a g n i t u d e relationship, was high: 1.77 ± 0.15. Furthermore, this p a r a m e t e r varied during the course of t h e swarm, a decrease in t h e b value f r om 1.8 to 1.1 being followed by a sharp increase to 2.5 a f t e r t h e largest earthquakes and principal volcanic eruption. Values of seismic moment were obtained from A B for 118 e a r t h q u a k es which were well recorded by long-period seismographs. Other source charact e r i s t i c s were determined from the difference between t h e l o g a r i t hm of seismic moment and the local magnitude. The source sizes were found to he u n u s u a l l y large. There was a t i m e variation of source properties during the swarm. The v a r i a t i o n of t h e displacement shows an inverse correlation with t h e variation of the coefficient b. The swarm produced very d i s t i n c t i v e T phases, well recorded at a hydrophone near Wake Island and at seismograph stations s i t u a t e d on t h e oceanic side of the Tonga Trench: these were not recorded at seismograph stations within the island arcs.

  8. Synthesis of hydrazine based novel HMG coA inhibitor and its docking studies

    Saravanan. B

    2013-12-01

    Full Text Available Heart attack is the recent attention to the medical sciences and cardiac low density cholesterol (LDL has a significant role in inhibiting the arrest. Various pathways having the keypoints which can interrupt the synthesis of bad cholesterol. In this study Hydrazine based compound is choosen due to its wide applications, the 1,2-Bis (2-hydroxy-5-methylbenzylidene - hydrazine crystals were synthesized. It was taken as a ligand for molecular docking. The target receptor used for docking is HMG-CoA reductase whose crystal structure is available on the PDB database as PDB ID: 1DQ8. For docking analysis, Autodock tool v4. 2 program used. The synthesized crystals are subjected to single crystal X-ray studies in order to investigate their molecular structure.

  9. Preliminary analysis of Stearoyl Co-A Desaturase gene transcripts in River buffalo

    L. Ramunno

    2010-02-01

    Full Text Available Stearoyl-CoA desaturase (SCD is a key enzyme in the biosynthesis of monounsaturated fatty acids (MUFAs. In cattle, SCD gene extends over a DNA segment of ~17.0 Kb, and it is organized in 6 exons and 5 introns. The SCD gene has been indicated as the candidate gene to change the saturated/unsaturated FAs ratio and hence it has been suggested as the gene influencing the fat quality. In cattle, eight SNPs have been identified and one of them, (T→C at 231st nt of 5th exon, is responsible for the Val→Ala amino acid change. The C allele has been associated with higher content of MUFAs in carcasses, and it is positively related to a higher index of desaturation (C18:0/C18:1 and C16:0/C16:1 in the milk. In this study, we report on preliminary results of analysis of transcripts of the SCD encoding gene in river buffalo. The electrophoretic analysis of the RT-PCR products and the subsequent sequencing showed at least five different populations of mRNA. The most represented population is correctly assembled (~1300 bp, followed by the one which is deleted of ~750bp, corresponding to the 3rd, 4th and 5th exon and partially to the 2nd and 6th exon.

  10. Grassland Conservation Opportunity Areas - Liberal Model (ECO_RES.COA_GRASS33)

    U.S. Environmental Protection Agency — This layer designates areas with potential for grassland conservation. These are areas of natural or semi-natural grass land cover patches that are at least 75...

  11. Forest Conservation Opportunity Areas - Liberal Model (ECO_RES.COA_FORREST33)

    U.S. Environmental Protection Agency — This layer designates areas with potential for forest conservation. These are areas of natural or semi-natural forest land cover patches that are at least 75 meters...

  12. Rehabilitation of an old palm-tree plantation in Ivory Coas

    Abodou Ake, N.

    1988-01-01

    Full Text Available In the "Sous-prefecture" of Anyama, South-east of Ivory Coast, an old palm-tree plantation run at village level had to be replaced by another activity such as cassava cultivation or broiler production. The success of such a rehabilitation is closely associated with an adequate choice of the new agricultural activity, with technical competence, with the acceptance of the new techniques and with an appropriate regional extension service. The conjunction of all these factors has made the operation a success. The poultry production is more profitable than cassava to substitute palm-oil plantation in the context concerned.

  13. Stearoyl CoA Desaturase Is Required to Produce Active, Lipid-Modified Wnt Proteins

    Jessica Rios-Esteves

    2013-09-01

    Full Text Available Wnt proteins contain palmitoleic acid, an unusual lipid modification. Production of an active Wnt signal requires the acyltransferase Porcupine and depends on the attachment of palmitoleic acid to Wnt. The source of this monounsaturated fatty acid has not been identified, and it is not known how Porcupine recognizes its substrate and whether desaturation occurs before or after fatty acid transfer to Wnt. Here, we show that stearoyl desaturase (SCD generates a monounsaturated fatty acid substrate that is then transferred by Porcupine to Wnt. Treatment of cells with SCD inhibitors blocked incorporation of palmitate analogs into Wnt3a and Wnt5a and reduced Wnt secretion as well as autocrine and paracrine Wnt signaling. The SCD inhibitor effects were rescued by exogenous addition of monounsaturated fatty acids. We propose that SCD is a key molecular player responsible for Wnt biogenesis and processing and that SCD inhibition provides an alternative mechanism for blocking Wnt pathway activation.

  14. New insights into structure-function relationships of oxalyl CoA decarboxylase from Escherichia coli.

    Werther, Tobias; Zimmer, Agnes; Wille, Georg; Golbik, Ralph; Weiss, Manfred S; König, Stephan

    2010-06-01

    The gene yfdU from Escherichia coli encodes a putative oxalyl coenzyme A decarboxylase, a thiamine diphosphate-dependent enzyme that is potentially involved in the degradation of oxalate. The enzyme has been purified to homogeneity. The kinetic constants for conversion of the substrate oxalyl coenzyme A by the enzyme in the absence and presence of the inhibitor coenzyme A, as well as in the absence and presence of the activator adenosine 5'-diphosphate, were determined using a novel continuous optical assay. The effects of these ligands on the solution and crystal structure of the enzyme were studied using small-angle X-ray scattering and X-ray crystal diffraction. Analyses of the obtained crystal structures of the enzyme in complex with the cofactor thiamine diphosphate, the activator adenosine 5'-diphosphate and the inhibitor acetyl coenzyme A, as well as the corresponding solution scattering patterns, allow comparison of the oligomer structures of the enzyme complexes under various experimental conditions, and provide insights into the architecture of substrate and effector binding sites. PMID:20553497

  15. How a Plant Lectin Recognizes High Mannose Oligosaccharides1[C][OA

    Garcia-Pino, Abel; Buts, Lieven; Wyns, Lode; Imberty, Anne; Loris, Remy

    2007-01-01

    The crystal structure of Pterocarpus angolensis seed lectin is presented in complex with a series of high mannose (Man) oligosaccharides ranging from Man-5 to Man-9. Despite that several of the nine Man residues of Man-9 have the potential to bind in the monosaccharide-binding site, all oligomannoses are bound in the same unique way, employing the tetrasaccharide sequence Manα(1–2)Manα(1–6)[Manα(1–3)]Manα(1–. Isothermal titration calorimetry titration experiments using Man-5, Man-9, and the Man-9-containing glycoprotein soybean (Glycine max) agglutinin as ligands confirm the monovalence of Man-9 and show a 4-times higher affinity for Man-9 when it is presented to P. angolensis seed lectin in a glycoprotein context. PMID:17556509

  16. Inaugural COA Forum Emphasizes the Importance of U.S. Foreign Policy in Africa

    Naval Postgraduate School Public Affairs Office

    2011-01-01

    The African continent has long been recognized as a vast land with nations in various stages of transition – some nations seek prosperity with planned pathways to it, while others are rife with instability and corruption. Without doubt, however, is that the United States, specifically the U.S. Africa Command (AFRICOM), has a role to play in bridging the gap between volatility, and stability.

  17. Identification of ten mevalonate enzyme-encoding genes and their expression in response to juvenile hormone levels in Leptinotarsa decemlineata (Say).

    Li, Qian; Meng, Qing-Wei; Lü, Feng-Gong; Guo, Wen-Chao; Li, Guo-Qing

    2016-06-15

    The mevalonate pathway is responsible for the biosynthesis of many essential molecules important in insect development, reproduction, chemical communication and defense. Based on Leptinotarsa decemlineata transcriptome and genome data, we identified ten genes that encoded acetoacetyl-CoA thiolase (LdAACT1 and LdAACT2), hydroxymethylglutaryl (HMA)-CoA synthase (LdHMGS), HMG-CoA reductase (LdHMGR1 and LdHMGR2), mevalonate kinase (LdMevK), phospho-mevalonate kinase (LdPMK), mevalonate diphosphate decarboxylase (LdMDD), isopentenyl-diphosphate isomerase (LdIDI) and farnesyl pyrophosphate synthetase (LdFPPS). Nine of these genes (except for LdAACT1) were mainly expressed in the larval brain-corpora cardiaca-corpora allata complex, and adult ovary and testis. The 9 genes were transcribed at high levels right after each ecdysis, and at low levels in the mid instar. Therefore, the 9 genes were indicated to be involved in JH biosynthesis. Moreover, knockdown of a JH biosynthesis gene LdJHAMT to lower JH titer significantly downregulated the transcription of the 9 genes. Ingestion of JH to activate JH signaling also significantly suppressed the expression of the 9 genes. It appears that the accumulation of JH precursors in LdJHAMT RNAi larvae and a high JH titer in JH-fed specimens may cause negative feedbacks to repress the expression of the 9 mevalonate enzyme-encoding genes (excluding LdAACT1) to balance the enzyme quantity in L. decemlineata. PMID:26899871

  18. Medium consumption reduction measures of sIack coaI processing system in Changping coaI preparation pIant%长平选煤厂末煤系统降低介耗的措施

    马彩雯

    2015-01-01

    In order to decrease medium consumption of slack coal processing system in Changping coal preparation plant,taking each link which consumed medium as research object,the causes of large medium consumption were analyzed from technology level and management level. The results showed that,imperfect medium recovery system of powder coal,poor effects of spraying screen and magnetic separator, nonstandard daily management of magnetite powder led to high medium consumption. The above problems were reformed by installing buff-er board in chute of spraying screen,setting up coal retaining plate at the inlet of spraying screen,adding spraying process in the middle of spraying screen,installing 10 pieces of 2 mm screen mesh in overflow launder,preremoving medium,building concentrated medium storage tank near the mixed medium bucket in the main plant,shortening medium addition pipe,regulating magnetite powder quality and use man-agement. After transformation,the medium consumption reduced from 2. 0 kg/ t to 1. 5 kg/ t,lower the production cost and increased the e-conomic benefits.%针对长平选煤厂末煤系统介耗高的问题,以介质流通各环节为基础,从介质的技术耗损和管理耗损2方面对介耗高的原因进行分析,提出了改造措施。结果表明,末煤介质回收系统不完善,磁选机回收效果差,矸石带走大量介质,脱介筛脱介效果差,磁铁矿粉质量不合格,磁铁矿粉的储运、添加方式不合理等是造成长平选煤厂末煤系统介耗高的主要原因。通过在脱介筛入料溜槽内加装缓冲板,在脱介筛入料端加装挡煤皮,在脱介筛中部加装1道喷水;在溢流方箱内加设10块2 mm 筛网,对物料进行预脱介;在主厂房合介桶旁边建浓介池,缩短加介管路;加强磁铁矿粉管理,严控磁铁矿粉质量等措施对长平选煤厂进行改造,使选煤厂末煤介耗由2.0 kg / t 降至1.5 kg / t,全年节约介质费用90.09万元。

  19. Mutations in COA3 cause isolated complex IV deficiency associated with neuropathy, exercise intolerance, obesity, and short stature

    Ostergaard, Elsebet; Weraarpachai, Woranontee; Ravn, Kirstine Johanne Theresia; Born, Alfred Peter; Jønson, Lars; Dunø, Morten; Wibrand, Flemming; Shoubridge, Eric A; Vissing, John

    2015-01-01

    BACKGROUND: We investigated a subject with an isolated cytochrome c oxidase (COX) deficiency presenting with an unusual phenotype characterised by neuropathy, exercise intolerance, obesity, and short stature. METHODS AND RESULTS: Blue-native polyacrylamide gel electrophoresis (BN-PAGE) analysis...

  20. Disruption of the acyl-coa binding protein gene delays hepatic adaptation to metabolic changes at weaning

    Neess, Ditte; Bloksgaard, Maria; Sørensen, Signe Bek; Marcher, Ann-Britt; Elle, Ida C; Helledie, Torben; Due, Marianne; Pagmantidis, Vasileios; Finsen, Bente; Wilbertz, Johannes; Kruhoeffer, Mogens; Faergeman, Nils; Mandrup, Susanne

    2011-01-01

    , little is known about the in vivo function in mammalian cells. We have generated mice with targeted disruption of ACBP (ACBP-/-). These mice are viable and fertile and develop normally. However, around weaning the ACBP-/- mice go through a crisis with overall weakness, and a slightly decreased growth...... rate. Using microarray analysis we show that the liver of ACBP-/- mice display a significantly delayed adaptation to weaning with late induction of target genes of the sterol regulatory element binding protein (SREBP) family. As a result, hepatic de novo cholesterogenesis is decreased at weaning. The...... delayed induction of SREBP target genes around weaning is caused by a compromised processing and decreased expression of SREBP precursors leading to reduced binding of SREBP to target sites in chromatin. In conclusion, lack of ACBP interferes with the normal metabolic adaptation to weaning and leads to...

  1. Dinuclear nickel complexes modeling the structure and function of the acetyl CoA synthase active site

    Ito, Mikinao; Kotera, Mai; Matsumoto, Tsuyoshi; Tatsumi, Kazuyuki

    2009-01-01

    A dinuclear nickel complex with methyl and thiolate ligands, Ni(dadtEt)Ni(Me)(SDmp) (2), has been synthesized as a dinuclear Nid–Nip-site model of acetyl-CoA synthase (ACS) (dadtEt is N,N′-diethyl-3,7-diazanonane-1,9-dithiolate; Dmp is 2,6-dimesitylphenyl). Complex 2 was prepared via 2 methods: (i) ligand substitution of a dinuclear Ni(II)–Ni(II) cation complex [Ni(dadtEt) Ni(tmtu)2] (OTf)2(1) with MeMgBr and KSDmp (tmtu is tetramethylthiourea), (ii) methyl transfer from methylcobaloxime Co(d...

  2. Underlying Resistance Mechanisms in the Cynosurus echinatus Biotype to Acetyl CoA Carboxylase-Inhibiting Herbicides

    Fernández, Pablo; Alcántara-de la Cruz, Ricardo; Cruz-Hipólito, Hugo; Osuna, María D.; Prado, Rafael

    2016-01-01

    Hedgehog dogtail (Cynosurus echinatus) is an annual grass, native to Europe, but also widely distributed in North and South America, South Africa, and Australia. Two hedgehog dogtail biotypes, one diclofop-methyl (DM)-resistant and one DM-susceptible were studied in detail for experimental dose-response resistance mechanisms. Herbicide rates that inhibited shoot growth by 50% (GR50) were determined for DM, being the resistance factor (GR50R/GR50S) of 43.81. When amitrole (Cyt. P450 inhibitor)...

  3. Underlying Resistance Mechanisms in the Cynosurus echinatus Biotype to Acetyl CoA Carboxylase-Inhibiting Herbicides.

    Fernández, Pablo; Alcántara-de la Cruz, Ricardo; Cruz-Hipólito, Hugo; Osuna, María D; De Prado, Rafael

    2016-01-01

    Hedgehog dogtail (Cynosurus echinatus) is an annual grass, native to Europe, but also widely distributed in North and South America, South Africa, and Australia. Two hedgehog dogtail biotypes, one diclofop-methyl (DM)-resistant and one DM-susceptible were studied in detail for experimental dose-response resistance mechanisms. Herbicide rates that inhibited shoot growth by 50% (GR50) were determined for DM, being the resistance factor (GR50R/GR50S) of 43.81. When amitrole (Cyt. P450 inhibitor) was applied before treatment with DM, the R biotype growth was significantly inhibited (GR50 of 1019.9 g ai ha(-1)) compared with the GR50 (1484.6 g ai ha(-1)) found for the R biotype without pretreatment with amitrole. However, GR50 values for S biotype do not vary with or without amitrole pretreatment. Dose-response experiments carried out to evaluate cross-resistance, showed resistance to aryloxyphenoxypropionate (APP), cyclohexanedione (CHD) and phenylpyrazoline (PPZ) inhibiting herbicides. Both R and S biotypes had a similar (14)C-DM uptake and translocation. The herbicide was poorly distributed among leaves, the rest of the shoot and roots with unappreciable acropetal and/or basipetal DM translocation at 96 h after treatment (HAT). The metabolism of (14)C-DM, D-acid and D-conjugate metabolites were identified by thin-layer chromatography. The results showed that DM resistance in C. echinatus is likely due to enhanced herbicide metabolism, involving Cyt. P450 as was demonstrated by indirect assays (amitrole pretreatment). The ACCase in vitro assays showed that the target site was very sensitive to APP, CHD and PPZ herbicides in the C. echinatus S biotype, while the R biotype was insensitive to the previously mentioned herbicides. DNA sequencing studies confirmed that C. echinatus cross-resistance to ACCase inhibitors has been conferred by specific ACCase double point mutations Ile-2041-Asn and Cys-2088-Arg. PMID:27148285

  4. Enzymes in the Mycobacterium tuberculosis MEP and CoA Pathways Targeted for Structure-Based Drug Design

    Björkelid, Christofer

    2012-01-01

    Tuberculosis, caused by the pathogenic bacteria Mycobacterium tuberculosis, is one of the most widespread and deadly infectious diseases today. Treatment of tuberculosis relies on antibiotics that were developed more than 50 years ago. These are now becoming ineffective due to the emergence of antibiotic resistant strains of the bacteria. The aim of the research in this thesis was to develop new antibiotics for tuberculosis treatment. To this end, we targeted enzymes from two essential biosyn...

  5. Single dose testosterone increases total cholesterol levels and induces the expression of HMG CoA Reductase

    Gårevik Nina

    2012-03-01

    Full Text Available Abstract Background Cholesterol is mainly synthesised in liver and the rate-limiting step is the reduction of 3-hydroxy-3methylglutaryl coenzyme A (HMG-CoA to mevalonate, a reaction catalysed by HMG-CoA reductase (HMGCR. There is a comprehensive body of evidence documenting that anabolic-androgenic steroids are associated with deleterious alterations of lipid profile. In this study we investigated whether a single dose of testosterone enanthate affects the cholesterol biosynthesis and the expression of HMGCR. Methods 39 healthy male volunteers were given 500 mg testosterone enanthate as single intramuscular dose of Testoviron®--Depot. The total cholesterol levels prior to and two days after testosterone administration were analysed. Protein expression of HMGCR in whole blood was investigated by Western blotting. In order to study whether testosterone regulates the mRNA expression of HMGCR, in vitro studies were performed in a human liver cell-line (HepG2. Results The total cholesterol level was significantly increased 15% two days after the testosterone injection (p = 0.007. This is the first time a perturbation in the lipoprotein profile is observed after only a single dose of testosterone. Moreover, the HMGCR mRNA and protein expression was induced by testosterone in vitro and in vivo, respectively. Conclusion Here we provide a molecular explanation how anabolic androgenic steroids may impact on the cholesterol homeostasis, i.e. via an increase of the HMGCR expression. Increasing knowledge and understanding of AAS induced side-effects is important in order to find measures for treatment and care of these abusers.

  6. Engineering of PHB synthesis causes improved elastic properties of flax fibers.

    Wróbel-Kwiatkowska, Magdalena; Zebrowski, Jacek; Starzycki, Michał; Oszmiański, Jan; Szopa, Jan

    2007-01-01

    Flax stem is a source of fiber used by the textile industry. Flax fibers are separated from other parts of stems in the process called retting and are probably the first plant fibers used by man for textile purposes (1). Nowadays flax cultivation is often limited because of its lower elastic property compared to cotton fibers. Thus the goal of this study was to increase the flax fiber quality using a transgenic approach. Expression of three bacterial genes coding for beta-ketothiolase (phb A), acetoacetyl-CoA reductase (phb B), and PHB synthase (phb C) resulted in poly-beta-hydroxybutyrate (PHB) accumulation in the plant stem. PHB is known as a biodegradable thermoplastic displaying chemical and physical properties similar to those of conventional plastics (i.e., polypropylene). The fibers isolated from transgenic flax plants cultivated in the field and synthesizing PHB were then studied for biomechanical properties. All measured parameters, strength, Young's modulus, and energy for failure of flax fibers, were significantly increased. Thus the substantial improvement in elastic properties of fibers from the transgenic line has been achieved. Since the acetyl CoA, substrate for PHB synthesis, is involved not only for energy production but also for synthesis of many cellular constituents, the goal of this study was also the analysis of those metabolites, which interfere with plant physiology and thus fiber quality. The analyzed plants showed that reduction in lignin, pectin, and hemicellulose levels resulted in increased retting efficiency. A significant increase in phenolic acids was also detected, and this was the reason for improved plant resistance to pathogen infection. However, a slight decrease in crop production was detected. PMID:17269698

  7. Increased long chain acyl-Coa synthetase activity and fatty acid import is linked to membrane synthesis for development of picornavirus replication organelles.

    Jules A Nchoutmboube

    Full Text Available All positive strand (+RNA viruses of eukaryotes replicate their genomes in association with membranes. The mechanisms of membrane remodeling in infected cells represent attractive targets for designing future therapeutics, but our understanding of this process is very limited. Elements of autophagy and/or the secretory pathway were proposed to be hijacked for building of picornavirus replication organelles. However, even closely related viruses differ significantly in their requirements for components of these pathways. We demonstrate here that infection with diverse picornaviruses rapidly activates import of long chain fatty acids. While in non-infected cells the imported fatty acids are channeled to lipid droplets, in infected cells the synthesis of neutral lipids is shut down and the fatty acids are utilized in highly up-regulated phosphatidylcholine synthesis. Thus the replication organelles are likely built from de novo synthesized membrane material, rather than from the remodeled pre-existing membranes. We show that activation of fatty acid import is linked to the up-regulation of cellular long chain acyl-CoA synthetase activity and identify the long chain acyl-CoA syntheatse3 (Acsl3 as a novel host factor required for polio replication. Poliovirus protein 2A is required to trigger the activation of import of fatty acids independent of its protease activity. Shift in fatty acid import preferences by infected cells results in synthesis of phosphatidylcholines different from those in uninfected cells, arguing that the viral replication organelles possess unique properties compared to the pre-existing membranes. Our data show how poliovirus can change the overall cellular membrane homeostasis by targeting one critical process. They explain earlier observations of increased phospholipid synthesis in infected cells and suggest a simple model of the structural development of the membranous scaffold of replication complexes of picorna-like viruses, that may be relevant for other (+RNA viruses as well.

  8. Transcriptional and Functional Analysis of Oxalyl-Coenzyme A (CoA) Decarboxylase and Formyl-CoA Transferase Genes from Lactobacillus acidophilus

    Azcarate-Peril, M. Andrea; Bruno-Bárcena, Jose M.; Hassan, Hosni M.; Klaenhammer, Todd R.

    2006-01-01

    Oxalic acid is found in dietary sources (such as coffee, tea, and chocolate) or is produced by the intestinal microflora from metabolic precursors, like ascorbic acid. In the human intestine, oxalate may combine with calcium, sodium, magnesium, or potassium to form less soluble salts, which can cause pathological disorders such as hyperoxaluria, urolithiasis, and renal failure in humans. In this study, an operon containing genes homologous to a formyl coenzyme A transferase gene (frc) and an ...

  9. Microbiota-Dependent Hepatic Lipogenesis Mediated by Stearoyl CoA Desaturase 1 (SCD1) Promotes Metabolic Syndrome in TLR5-Deficient Mice.

    Singh, Vishal; Chassaing, Benoit; Zhang, Limin; San Yeoh, Beng; Xiao, Xia; Kumar, Manish; Baker, Mark T; Cai, Jingwei; Walker, Rachel; Borkowski, Kamil; Harvatine, Kevin J; Singh, Nagendra; Shearer, Gregory C; Ntambi, James M; Joe, Bina; Patterson, Andrew D; Gewirtz, Andrew T; Vijay-Kumar, Matam

    2015-12-01

    The gut microbiota plays a key role in host metabolism. Toll-like receptor 5 (TLR5), a flagellin receptor, is required for gut microbiota homeostasis. Accordingly, TLR5-deficient (T5KO) mice are prone to develop microbiota-dependent metabolic syndrome. Here we observed that T5KO mice display elevated neutral lipids with a compositional increase of oleate [C18:1 (n9)] relative to wild-type littermates. Increased oleate contribution to hepatic lipids and liver SCD1 expression were both microbiota dependent. Analysis of short-chain fatty acids (SCFAs) and (13)C-acetate label incorporation revealed elevated SCFA in ceca and hepatic portal blood and increased liver de novo lipogenesis in T5KO mice. Dietary SCFAs further aggravated metabolic syndrome in T5KO mice. Deletion of hepatic SCD1 not only prevented hepatic neutral lipid oleate enrichment but also ameliorated metabolic syndrome in T5KO mice. Collectively, these results underscore the key role of the gut microbiota-liver axis in the pathogenesis of metabolic diseases. PMID:26525535

  10. A single nucleotide polymorphism in the promoter region of river buffalo stearoyl CoA desaturase gene (SCD) is associated with milk yield.

    Pauciullo, Alfredo; Cosenza, Gianfranco; Steri, Roberto; Coletta, Angelo; La Battaglia, Antonio; Di Berardino, Dino; Macciotta, Nicolò P P; Ramunno, Luigi

    2012-11-01

    An association study between the milk yield trait and the stearoyl-CoA desaturase (SCD) polymorphism (g.133A > C) in Italian Mediterranean river buffalo was carried out. A full characterization of the river buffalo SCD promoter region was presented. Genotyping information was provided and a quick method for allelic discrimination was developed. The frequency of the C allele was 0·16. Test-day (TD) records (43 510) of milk production belonging to 226 lactations of 169 buffalo cows were analysed with a mixed linear model in order to estimate the effect of g.133A > C genotype, as well as the effect of parity and calving season. The SCD genotype was significantly associated with milk yield (P = 0·02). The genotype AC showed an over-dominance effect with an average daily milk yield approximately 2 kg/d higher than CC buffaloes. Such a difference represents about 28% more milk/d. The effect of the genotype was constant across lactation stages. The contribution of SCD genotype (r(2)SCD) to the total phenotypic variance in milk yield was equal to 0·12. This report is among the first indications of genetic association between a trait of economic importance in river buffalo. Although such results need to be confirmed with large-scale studies in the same and other buffalo populations, they might offer useful indications for the application of MAS programmes in river buffalo and in the future they might be of great economic interest for the river buffalo dairy industry. PMID:22994977

  11. STEAROYL-COA DESATURASE GENE TRANSCRIPTION, mRNA, AND ACTIVITY IN RESPONSE TO TRANS-VACCENIC ACID AND CONJUGATED LINOLEIC ACID ISOMERS

    Lin, Xiaobo

    2000-01-01

    Studies were conducted to investigate: 1) desaturation of dietary trans-vaccenic acid (TVA, trans11-18:1) to the cis9,trans11-18:2 isomer of conjugated linoleic acid (9/11CLA), 2) effects of two conjugated linoleic acid isomers [9/11CLA or trans10,cis12-18:2 (10/12CLA)] and TVA on enzyme activities and mRNA abundance for lipogenic enzymes, and 3) regulation of stearoyl-CoA desaturase (SCD) gene transcription. In the first study, lactating mice were fed 3% linoleic acid (LA...

  12. Lignin and Fiber digestibility in Caffeic Acid 3-O-Methyltransferase and Caffeoyl CoA 3-O-Methyltransferase Downregulated Alfalfa

    Alfalfa (Medicago sativa L.) is one of the most important forages in the United States. Increasing alfalfa fiber digestibility would improve forage management and ration formulation flexibility. Currently, growers and breeders rely on near infrared spectroscopy (NIRS) to predict forage quality tra...

  13. DISTINCT TRANSCRIPTIONAL REGULATION OF LONG-CHAIN ACYL-COA SYNTHETASE ISOFORMS AND CYTOSOLIC THIOESTERASE 1 IN THE RODENT HEART BY FATTY ACIDS AND INSULIN

    The molecular mechanism(s) responsible for channeling long-chain fatty acids (LCFAs) into oxidative versus nonoxidative pathways is (are) poorly understood in the heart. Intracellular LCFAs are converted to long-chain fatty acyl-CoAs (LCFA-CoAs) by a family of long-chain acyl-CoA synthetases (ACSLs)...

  14. HMG CoA Lyase (HL): Mutation detection and development of a bacterial expression system for screening the activity of mutant alleles from HL-deficient patients

    Robert, M.F.; Ashmarina, L.; Poitier, E. [Hospital Ste-Justine, Montreal (Canada)] [and others

    1994-09-01

    HL catalyzes the last step of ketogenesis, and autosomal recessive HL deficiency in humans can cause episodes of hypoglycemia and coma. Structurally, HL is a dimer of identical 325-residue peptides which requires a reducing environment to maintain activity. We cloned the human and mouse HL cDNAs and genes and have performed mutation analysis on cells from 30 HL-deficient probands. Using SSCP and also genomic Southern analysis we have identified putative mutations on 53/60 alleles of these patients (88%). To date, we have found 20 mutations: 3 large deletions, 4 termination mutations, 5 frameshift mutations, and 8 missense mutations which we suspect to be pathogenic based on evolutionary conservation and/or our previous studies on purified HL protein. We have also identified 3 polymorphic variants. In order to directly test the activity of the missense mutations, we established a pGEX-based system, using a glutathione S transferase (GST)-HL fusion protein. Expressed wild-type GST-HL was insoluble. We previously located a reactive Cys at the C-terminus of chicken HL which is conserved in human HL. We produced a mutant HL peptide, C323S, which replaced Cys323 with Ser. Purified C323S is soluble and has similar kinetics to wild-type HL. C323S-containing GST-HL is soluble and enzymatically active. We are cloning and expressing the 8 missense mutations.

  15. AppIication of fine coaI dry screening process%末煤干法脱粉工艺的应用

    李燕; 李瑞丰; 陶健

    2015-01-01

    为减少进入煤泥水系统的煤泥量,简化煤泥水处理系统,提高产品发热量,提高企业的经济效益。采用增加末煤干法脱粉工艺的方法对海湾选煤厂进行改造。通过比较分析可知,增加末煤干法脱粉工艺可预先脱除原生煤泥,减少煤泥入水量,降低煤泥处理系统负荷,简化煤泥处理工艺,降低煤泥处理费用,同时旁路煤泥可作为产品掺入末煤产品,企业年销售收入增加829.22万元,具有较高的经济效益。%In order to decrease slime content,lower handing capacity of slime treatment system,improve products calorific value and eco-nomic benefits,the original process of Haiwan coal preparation plant was transformed by adding fine coal dry screening process. The results showed that,the newly installed process could remove primary slime in advance,so less slime leaked into circulating water. The slime treat-ment process was simplified and the handing expense was decreased. The slime in the bypass could be mixed in fine coal. The plant in-creased sales revenue by RMB 8. 2922x106 .

  16. Acyl CoA Binding Domain Containing 3 (ACBD3) Protein in Huntington’s Disease 
Human Skin Fibroblasts

    Kratochvílová, H.; Rodinová, M.; Sládková, J.; Klempíř, J.; Lišková, Irena; Motlík, Jan; Zeman, J.; Hansíková, H.; Tesařová, M.

    2015-01-01

    Roč. 78, Suppl. 2 (2015), s. 34-38. ISSN 1210-7859. [Conference on Animal Models for neurodegenerative Diseases /3./. Liblice, 08.11.2015-10.11.2015] R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : Huntington’s disease * Acyl-CoA binding domain containing 3 protein * human skin fibroblasts Subject RIV: FH - Neurology Impact factor: 0.165, year: 2014

  17. Association between HMG CoA reductase inhibitors and anxiety: an experimental study using elevated plus maze and light dark arena behavioural models

    Anupama M. Gudadappanavar

    2015-06-01

    Results: Going through the results of this study an evidence for the association between lowered serum cholesterol and symptoms of anxiety can be seen as statins used in the present study failed to show significant anxiolytic effect when compared to standard but in turn showed even more less activity when compared to control, indicating anxiogenic behavior. Conclusions: Our findings support the evidence of the negative effects of statins on psychological outcomes. Its generally understood that having low cholesterol is a good health sign, combined with other factors; it could actually put a person at risk by causing anxiety and stress. Further research comprising a greater number of studies is required to confirm the effects of this agent on psychological outcomes. [Int J Res Med Sci 2015; 3(6.000: 1329-1335

  18. Regulation of Polyhydroxybutyrate Synthesis in the Soil Bacterium Bradyrhizobium diazoefficiens.

    Quelas, J I; Mesa, S; Mongiardini, E J; Jendrossek, D; Lodeiro, A R

    2016-07-15

    Polyhydroxybutyrate (PHB) is a carbon and energy reserve polymer in various prokaryotic species. We determined that, when grown with mannitol as the sole carbon source, Bradyrhizobium diazoefficiens produces a homopolymer composed only of 3-hydroxybutyrate units (PHB). Conditions of oxygen limitation (such as microoxia, oxic stationary phase, and bacteroids inside legume nodules) were permissive for the synthesis of PHB, which was observed as cytoplasmic granules. To study the regulation of PHB synthesis, we generated mutations in the regulator gene phaR and the phasin genes phaP1 and phaP4 Under permissive conditions, mutation of phaR impaired PHB accumulation, and a phaP1 phaP4 double mutant produced more PHB than the wild type, which was accumulated in a single, large cytoplasmic granule. Moreover, PhaR negatively regulated the expression of phaP1 and phaP4 as well as the expression of phaA1 and phaA2 (encoding a 3-ketoacyl coenzyme A [CoA] thiolases), phaC1 and phaC2 (encoding PHB synthases), and fixK2 (encoding a cyclic AMP receptor protein [CRP]/fumarate and nitrate reductase regulator [FNR]-type transcription factor of genes for microoxic lifestyle). In addition to the depressed PHB cycling, phaR mutants accumulated more extracellular polysaccharides and promoted higher plant shoot dry weight and competitiveness for nodulation than the wild type, in contrast to the phaC1 mutant strain, which is defective in PHB synthesis. These results suggest that phaR not only regulates PHB granule formation by controlling the expression of phasins and biosynthetic enzymes but also acts as a global regulator of excess carbon allocation and symbiosis by controlling fixK2 IMPORTANCE: In this work, we investigated the regulation of polyhydroxybutyrate synthesis in the soybean-nodulating bacterium Bradyrhizobium diazoefficiens and its influence in bacterial free-living and symbiotic lifestyles. We uncovered a new interplay between the synthesis of this carbon reserve polymer

  19. SYNTHESIS, CROSSLINKING MECHANISM AND PROPERTIES OF A POLYACRYLATE/POLYURETHANE COMPOSITE COATING

    TANG Liming; GUO Wei; ZHOU Qixiang

    1997-01-01

    A polyacrylate/polyurethane (P(A)/P(U)) composite coating has been prepared by crosslinking an acetoacetylated polyacrylate with a vinylic group terminated polyurethane at room temperature. A model Michael reaction between ethyl acetoacetate (EAA) and methyl acrylate (MA) was designed to study the crosslinking mechanism. It was found that the two active hydrogen atoms in acetoacetyl group can both add to vinylic groups and the yield of mono- and bis-adducts are much affected by the molar ratio of acetoacetyl to vinylic groups. Higher crosslinking degree and better properties could be obtained with decreasing the molar ratio of the two active groups from 1/1 to 0.6/1 in the composite coatings.

  20. Approach to Energy Conservation and Consumption Reduction in Power Supply System in Coal Preparation Plan, Yangquan Coa%选煤厂供电系统节能降耗的有效途径

    卢宏龙

    2011-01-01

    In the paper the author discusses several approaches to energy conservation and consumption reduction in coal preparation plant and analyzes the three effective approaches in power supply system in Coal Preparation Plant, Yangquan Coal Group, which can be%讨论选煤厂节能降耗的几种主要途径,并分析了阳煤集团选煤厂供电系统节能降耗的三种有效途径,对选煤厂节能降耗借鉴意义。

  1. AppIication of fIip-fIow screen in deep cIassification of steam coaI%弛张筛在动力煤深度分级中的应用

    刘文统

    2015-01-01

    基于弛张筛对动力煤的深度分级作用,阐述了动力煤深度分级后对生产工艺的优化,提出了分选动力煤的新工艺。对于全级入选的动力煤选煤厂,一是解决了煤泥减量化生产瓶颈,避免大量煤泥造成的后续处理问题,二是实现了末煤可以灵活地选择进入块煤分选系统分选或末煤分选系统分选,三是实现了粉煤可以灵活地选择进入水洗系统分选或直接作为末煤产品;对于仅入选块煤的选煤厂进行原煤深度分级后,降低了块煤分选下限,增加了块煤入选量,解决了动力煤〈25 mm 粒级煤不能进入重介浅槽分选机分选的技术难题。%Based on the application of flip-flow screen in deep classification of steam coal,the optimization of process was introduced. For the coal preparation plants which prepared the whole grade steam coal,the application decreased the slime production,made the fine coal separate in lump coal separation system or fine coal separation system flexibly,let the pulverized coal go into water wash system or be sold as fine coal. For the coal preparation plants which only prepared lump coal,the application reduced the lower limit of separation,increased the separation amount of the lump coal,realized -25 mm steam coal could be separated by dense medium shallow slot cyclone.

  2. Oxalate-Degrading Activity in Bifidobacterium animalis subsp. lactis: Impact of Acidic Conditions on the Transcriptional Levels of the Oxalyl Coenzyme A (CoA) Decarboxylase and Formyl-CoA Transferase Genes ▿

    Turroni, Silvia; Bendazzoli, Claudia; Dipalo, Samuele C. F.; Candela, Marco; Vitali, Beatrice; Gotti, Roberto; Brigidi, Patrizia

    2010-01-01

    Oxalic acid occurs extensively in nature and plays diverse roles, especially in pathological processes. Due to its highly oxidizing effects, hyperabsorption or abnormal synthesis of oxalate can cause serious acute disorders in mammals and can be lethal in extreme cases. Intestinal oxalate-degrading bacteria could therefore be pivotal in maintaining oxalate homeostasis and reducing the risk of kidney stone development. In this study, the oxalate-degrading activities of 14 bifidobacterial strai...

  3. Computational study of the three-dimensional structure of N-acetyltransferase 2-acetyl coenzyme a complex.

    Oda, Akifumi; Kobayashi, Kana; Takahashi, Ohgi

    2010-01-01

    N-Acetyltransferase 2 (NAT2) is one of the most important polymorphic drug-metabolizing enzymes and plays a significant role in individual differences of drug efficacies and/or side effects. Coenzyme A (CoA) is a cofactor in the experimentally determined crystal structure of NAT2, although the acetyl source of acetylation reactions catalyzed by NAT is not CoA, but rather acetyl CoA. In this study, the three-dimensional structure of NAT2, including acetyl CoA, was calculated using molecular dynamics simulation. By substituting acetyl CoA for CoA the amino acid residue Gly286, which is known to transform into a glutamate residue by NAT2*7A and NAT2*7B, comes close to the cofactor binding site. In addition, the binding pocket around the sulfur atom of acetyl CoA expanded in the NAT2-acetyl CoA complex. PMID:20930369

  4. Sequence Classification: 389172 [

    Full Text Available BLE SUCCINYL-COA:3-KETOACID-COENZYME A TRANSFERASE (BETA SUBUNIT) SCOB (3-OXO-ACID:COA TRANSFERASE) (OXCT B)... (SUCCINYL CoA:3-OXOACID CoA-TRANSFERASE) || http://www.ncbi.nlm.nih.gov/protein/31793683 ...

  5. Sequence Classification: 398926 [

    Full Text Available BLE SUCCINYL-COA:3-KETOACID-COENZYME A TRANSFERASE (BETA SUBUNIT) SCOB (3-OXO-ACID:COA TRANSFERASE) (OXCT B)... (SUCCINYL CoA:3-OXOACID CoA-TRANSFERASE) || http://www.ncbi.nlm.nih.gov/protein/15609640 ...

  6. Children of Alcoholics: A School-Based Comparative Study.

    Morey, Connie K.

    1999-01-01

    Examines differences between 4th-6th grade children of alcoholics (COAs) and non-COAs on measures of internalized shame, self-esteem, perceived support, and teacher behavior ratings. No significant differences were found on measures of social support and shame; however self-esteem and teacher ratings for COAs were significantly lower. Gender…

  7. The Basolateral Amygdala Is Necessary for the Encoding and the Expression of Odor Memory

    Sevelinges, Yannick; Desgranges, Bertrand; Ferreira, Guillaume

    2009-01-01

    Conditioned odor avoidance (COA) results from the association between a novel odor and a delayed visceral illness. The present experiments investigated the role of the basolateral amygdala (BLA) in acquisition and retrieval of COA memory. To address this, we used the GABAA agonist muscimol to temporarily inactivate the BLA during COA acquisition…

  8. Sequence Classification: 387888 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31792399|ref|NP_854892.1| PROBABLE FATTY-ACID...-COA LIGASE FADD6 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31792399 ...

  9. Sequence Classification: 387875 [

    Full Text Available TMB Non-TMH Non-TMB TMB Non-TMB Non-TMB >gi|31792386|ref|NP_854879.1| PROBABLE FATTY-ACID...-COA LIGASE FADD36 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31792386 ...

  10. Sequence Classification: 386881 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31791392|ref|NP_853885.1| PROBABLE FATTY-ACID...-COA LIGASE FADD4 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31791392 ...

  11. Sequence Classification: 390489 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31795000|ref|NP_857493.1| PROBABLE FATTY-ACID...-COA LIGASE FADD23 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31795000 ...

  12. Sequence Classification: 386766 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31791277|ref|NP_853770.1| POSSIBLE FATTY-ACID...-COA LIGASE FADD10 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31791277 ...

  13. Sequence Classification: 390226 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31794737|ref|NP_857230.1| PROBABLE FATTY-ACID...-COA LIGASE FADD3 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31794737 ...

  14. Sequence Classification: 390464 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31794975|ref|NP_857468.1| PROBABLE FATTY-ACID...-COA LIGASE FADD32 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE || http://www.ncbi.nlm.nih.gov/protein/31794975 ...

  15. Sequence Classification: 387222 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31791733|ref|NP_854226.1| PROBABLE FATTY-ACID...-COA LIGASE FADD8 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31791733 ...

  16. Sequence Classification: 386786 [

    Full Text Available Non-TMB Non-TMH TMB Non-TMB Non-TMB Non-TMB >gi|31791297|ref|NP_853790.1| PROBABLE FATTY-ACID...-COA LIGASE FADD7 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31791297 ...

  17. Sequence Classification: 387070 [

    Full Text Available Non-TMB TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31791581|ref|NP_854074.1| PROBABLE FATTY-ACID...-COA LIGASE FADD30 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31791581 ...

  18. Sequence Classification: 390179 [

    Full Text Available Non-TMB TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31794690|ref|NP_857183.1| PROBABLE FATTY-ACID...-COA LIGASE FADD19 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31794690 ...

  19. Sequence Classification: 387529 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31792040|ref|NP_854533.1| POSSIBLE FATTY-ACID...-COA LIGASE FADD16 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31792040 ...

  20. Sequence Classification: 389174 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31793685|ref|NP_856178.1| PROBABLE FATTY-ACID...-COA LIGASE FADD35 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31793685 ...

  1. Sequence Classification: 390171 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31794682|ref|NP_857175.1| POSSIBLE FATTY-ACID...-COA SYNTHETASE FADD17 (FATTY-ACID-COA SYNTHASE) (FATTY-ACID-COA LIGASE) || http://www.ncbi.nlm.nih.gov/protein/31794682 ...

  2. Sequence Classification: 388224 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31792735|ref|NP_855228.1| POSSIBLE FATTY-ACID...-COA LIGASE FADD11 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31792735 ...

  3. Sequence Classification: 386701 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31791212|ref|NP_853705.1| PROBABLE FATTY-ACID...-COA LIGASE FADD34 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31791212 ...

  4. Metabolic biology of 3-methylglutaconic acid-uria: a new perspective

    Su, Betty; Ryan, Robert O.

    2014-01-01

    Over the past twenty-five years a growing number of distinct syndromes / mutations associated with compromised mitochondrial function have been identified that share a common feature: urinary excretion of 3-methylglutaconic acid (3MGA). In the leucine degradation pathway, carboxylation of 3-methylcrotonyl CoA leads to formation of 3-methylglutaconyl CoA while 3-methylglutaconyl CoA hydratase converts this metabolite to 3-hydroxy-3-methylglutaryl CoA (HMG CoA). In “primary” 3MGA-uria, mutation...

  5. Characteristics of children of alcoholics: putative risk factors, substance use and abuse, and psychopathology.

    Sher, K J; Walitzer, K S; Wood, P K; Brent, E E

    1991-11-01

    A sample of 253 children of alcoholics (COAs) and 237 children of nonalcoholics (non-COAs) were compared on alcohol and drug use, psychopathology, cognitive ability, and personality. COAs reported more alcohol and drug problems, stronger alcohol expectancies, higher levels of behavioral undercontrol and neuroticism, and more psychiatric distress in relation to non-COAs. They also evidenced lower academic achievement and less verbal ability than non-COAs. COAs were given Diagnostic Interview Schedule alcohol diagnoses more frequently than non-COAs. The relation between paternal alcoholism and offspring alcohol involvement was mediated by behavioral undercontrol and alcohol expectancies. Although gender differences were found, there were few Gender X Family History interactions; the effects of family history of alcoholism were similar for men and women. When gender effects were found, they showed greater family history effects for women. PMID:1757657

  6. Generation and characterization of monoclonal antibodies specific to Coenzyme A

    Malanchuk O. M.

    2015-06-01

    Full Text Available Aim. Generation of monoclonal antibodies specific to Coenzyme A. Methods. Hybridoma technique. KLH carrier protein conjugated with CoA was used for immunization. Screening of positive clones was performed with BSA conjugated to CoA. Results. Monoclonal antibody that specifically recognizes CoA and CoA derivatives, but not its precursors ATP and cysteine has been generated. Conclusion. In this study, we describe for the first time the production and characterization of monoclonal antibodies against CoA. The monoclonal antibody 1F10 was shown to recognize specifically CoA in Western blotting, ELISA and immunoprecipitation. These properties make this antiboby a particularly valuable reagent for elucidating CoA function in health and disease.

  7. Pantethine rescues phosphopantothenoylcysteine synthetase and phosphopantothenoylcysteine decarboxylase deficiency in Escherichia coli but not in Pseudomonas aeruginosa.

    Balibar, Carl J; Hollis-Symynkywicz, Micah F; Tao, Jianshi

    2011-07-01

    Coenzyme A (CoA) plays a central and essential role in all living organisms. The pathway leading to CoA biosynthesis has been considered an attractive target for developing new antimicrobial agents with novel mechanisms of action. By using an arabinose-regulated expression system, the essentiality of coaBC, a single gene encoding a bifunctional protein catalyzing two consecutive steps in the CoA pathway converting 4'-phosphopantothenate to 4'-phosphopantetheine, was confirmed in Escherichia coli. Utilizing this regulated coaBC strain, it was further demonstrated that E. coli can effectively metabolize pantethine to bypass the requirement for coaBC. Interestingly, pantethine cannot be used by Pseudomonas aeruginosa to obviate coaBC. Through reciprocal complementation studies in combination with biochemical characterization, it was demonstrated that the differential characteristics of pantethine utilization in these two microorganisms are due to the different substrate specificities associated with endogenous pantothenate kinase, the first enzyme in the CoA biosynthetic pathway encoded by coaA in E. coli and coaX in P. aeruginosa. PMID:21551303

  8. Pantethine Rescues Phosphopantothenoylcysteine Synthetase and Phosphopantothenoylcysteine Decarboxylase Deficiency in Escherichia coli but Not in Pseudomonas aeruginosa▿†

    Balibar, Carl J.; Hollis-Symynkywicz, Micah F.; Tao, Jianshi

    2011-01-01

    Coenzyme A (CoA) plays a central and essential role in all living organisms. The pathway leading to CoA biosynthesis has been considered an attractive target for developing new antimicrobial agents with novel mechanisms of action. By using an arabinose-regulated expression system, the essentiality of coaBC, a single gene encoding a bifunctional protein catalyzing two consecutive steps in the CoA pathway converting 4′-phosphopantothenate to 4′-phosphopantetheine, was confirmed in Escherichia coli. Utilizing this regulated coaBC strain, it was further demonstrated that E. coli can effectively metabolize pantethine to bypass the requirement for coaBC. Interestingly, pantethine cannot be used by Pseudomonas aeruginosa to obviate coaBC. Through reciprocal complementation studies in combination with biochemical characterization, it was demonstrated that the differential characteristics of pantethine utilization in these two microorganisms are due to the different substrate specificities associated with endogenous pantothenate kinase, the first enzyme in the CoA biosynthetic pathway encoded by coaA in E. coli and coaX in P. aeruginosa. PMID:21551303

  9. Complications of Aortic Stenting in Patients below 20 Years Old: Immediate and Intermediate Follow-Up

    Akbar Molaei

    2011-12-01

    Full Text Available Background: Optimal timing and mode of treatment for patients with coarctation of the aorta (COA remain controversial, particularly in children. Surgery, balloon dilatation, and stent implantation have all proven effective in the treatment of moderate or severe obstruction. The aim of this study was to investigate the complications of COA stenting angioplasty in pediatric patients. Methods: This retrospective, descriptive study was conducted on patients less than 20 years of age who underwent aortic stenting angioplasty because of congenital COA in the pediatric catheterization laboratory of Rajaie cardiovascular, medical and research Center, Tehran between 2005 and 2010. Results: A total of 26 patients (18 [65.4%] males and 9 [34.6%] females with congenital COA who had undergone aortic stenting angioplasty were recruited. Nineteen (73.1% of these patients had native COA and 7 (26.9% had recurrent COA. Most of the early complications were minor and temporary; only one patient developed early major complications. During the follow-up, whereas none of the native group patients developed late complications, in the re-COA group 28.57% of the patients had re-stenosis and 14.28% had chronic systemic hypertension, requiring drug therapy. Conclusion: Our investigation into post-stenting complications in patients with native COA and re-COA showed that endovascular stenting could be an effective and safe method, even in young patients with native COA.

  10. GenBank blastx search result: AK061948 [KOME

    Full Text Available AK061948 001-042-E07 AF267243.2 Azotobacter vinelandii PhbF (phbF), putative phasin protein PhbP (phb...P), putative transcription activator PhbR (phbR), acetoacetyl-CoA reductase (phbB), polyhy...droxybutyrate biosynthetic beta-ketothiolase (phbA), and PHB synthase (phbC) genes, complete cds.|BCT BCT 1e-56 +3 ...

  11. GenBank blastx search result: AK059654 [KOME

    Full Text Available AK059654 001-031-C10 AF267243.2 Azotobacter vinelandii PhbF (phbF), putative phasin protein PhbP (phb...P), putative transcription activator PhbR (phbR), acetoacetyl-CoA reductase (phbB), polyhy...droxybutyrate biosynthetic beta-ketothiolase (phbA), and PHB synthase (phbC) genes, complete cds.|BCT BCT 3e-82 +1 ...

  12. Evaluation of Critical Operating Conditions for a Semi-batch Reactor by Complementary Use of Sensitivity and Divergence Criteria

    De Maria, G.; Stefan, D.-N.

    2011-01-01

    This paper presents a comparison of several effective methods of deriving the critical feeding conditions for the case of a semi-batch catalytic reactor used for the acetoacetylation of pyrrole with diketene in homogeneous liquid phase. The reaction is known to be of high risk due to the very exothermic (polymerisation) side-reactions involving reactive diketene. In order to perform the sensitivity analysis, both the Morbidelli-Varma sensitivity criterion and div-methods were used, the latter...

  13. Fluorescently labelled bovine acyl-CoA-binding protein acting as an acyl-CoA sensor: interaction with CoA and acyl-CoA esters and its use in measuring free acyl-CoA esters and non-esterified fatty acids

    Wadum, M.C.; Villadsen, J.K.; Feddersen, S.;

    2002-01-01

    Long-chain acyl-CoA esters are key metabolites in lipid synthesis and b-oxidation but, at the same time, are important regulators of intermediate metabolism, insulin secretion, vesicular trafficking and gene expression. Key tools in studying the regulatory functions of acyl-CoA esters are reliable...... methods for the determination of free acyl-CoA concentrations. No such method is presently available. In the present study, we describe the synthesis of two acyl-CoA sensors for measuring free acyl-CoA concentrations using acyl-CoA-binding protein as a scaffold. Met24 and Ala53 of bovine acyl......-CoA-binding protein were replaced by cysteine residues, which were covalently modified with 6-bromoacetyl-2-dimethylaminonaphthalene to make the two fluorescent acyl-CoA indicators (FACIs) FACI-24 and FACI-53. FACI-24 and FACI-53 showed fluorescence emission maximum at 510 and 525nm respectively, in the absence of...

  14. Cloning and sequence analysis of α-succinyl CoA synthetase B gene from Trichomonas vaginalis%阴道毛滴虫琥珀酰辅酶A合成酶基因的克隆与序列分析

    张昕鑫; 张西臣; 李建华; 宫鹏涛; 张国才; 杨举

    2008-01-01

    目的 获取阴道毛滴虫琥珀酰辅酶A合成酶(α-SCSB)全基因,并对其进行序列分析. 方法 利用PCR技术扩增阴道毛滴虫琥珀酰辅酶A合成酶(α-SCSB)全基因,并将其插入pMD18-T载体,酶切鉴定后进行序列测定及分析. 结果 PCR扩增获得α-SCSB全长基因,大小为1 381 bp,与国外发表的阴道毛滴虫琥珀酰辅酶A合成酶(α-SCSB)的基因同源性为100%. 结论 本研究获得了阴道毛滴虫琥珀酰辅酶A合成酶(α-SCSB)启动子,为下一步研究α-SCSB启动子的功能及构建阴道毛滴虫DNA稳定转染载体奠定了基础.

  15. His-234是毛白杨对香豆酸∶CoA连接酶的重要酶催化活性残基%His-234 is an Essential Residue for Populus tomentosa 4-coumarate ∶ CoA Ligase Enzymatic Mechanisms

    任百光; 李德峰; 郑彩霞; 盖颖; 蒋湘宁; 胡永林

    2013-01-01

    对香豆酸∶CoA连接酶(4-coumarate∶ coenzyme A ligase,4CL)是植物苯丙烷类代谢途径中的一个重要的酶.4CL以肉桂酸衍生物(香豆酸、咖啡酸、阿魏酸等)、ATP和CoA为底物合成相应的酰基-CoA酯,这些酰基-CoA酯是一系列重要化合物(如木质素)的前体.4CL的酶催化反应分两步进行:第一步以肉桂酸衍生物和Mg2+-ATP为底物合成酰基-AMP,第二步用CoA取代AMP,产生酰基-CoA酯,催化过程中酶的构象产生明显的变化.因为4CL在木质素的合成中所起的作用,这个酶是通过蛋白质工程方法改进林产品质量的重要靶标.我们通过X射线衍射技术,解析了毛白杨对香豆酸∶CoA连接酶l(Pt4CLl)与其中间产物对香豆酰-AMP的复合物晶体结构,与同家族成员结构比对,确定所获得的蛋白质结构为Pt4CL1催化第二步反应,即酰基-CoA酯合成的构象.结构分析表明:His-234残基在Pt4CL1的酶催化机理中起着多重作用,即通过侧链与AMP磷酸基团形成氢键,降低磷酸基团的负电荷,催化CoA的亲核取代反应;侧链可以采取两种不同的构象以调节CoA进入Pt4CL1的催化中心;His-234的侧链还可能夺取CoA巯基的质子,从而增强CoA的亲核反应活性.突变体酶活数据结果也显示His-234对Pt4CL1的活性非常重要,是Pt4CL1催化中心的活性残基.

  16. GETDB: 113367 [GETDB

    Full Text Available 113367 Link to Original w[*]; P{GawB}NP3604 / CyO, P{UAS-lacZ.UW14}UW14 60A6 Link t...o DGRC Genome Viewer: 113367 Thiolase ken 297{}879 3604 2 FlyBase Insertion: P{GawB}NP3604 NP line. Received... - - - d1 - - - Show 113367 DGRC Number 113367 Link to Original Genotype w[*]; P{GawB}NP3604 / CyO, P{UAS-la...cZ.UW14}UW14 Insertion Site 60A6 Map Viewer Link to DGRC Genome Viewer: 113367 Related Genes Thiolase ken 29...uest - AS ubiquitous wing pouch, epi, tr, gut, mt ubiquitous. strong in bristles.

  17. Identification of mitochondrial coenzyme a transporters from maize and Arabidopsis.

    Zallot, Rémi; Agrimi, Gennaro; Lerma-Ortiz, Claudia; Teresinski, Howard J; Frelin, Océane; Ellens, Kenneth W; Castegna, Alessandra; Russo, Annamaria; de Crécy-Lagard, Valérie; Mullen, Robert T; Palmieri, Ferdinando; Hanson, Andrew D

    2013-06-01

    Plants make coenzyme A (CoA) in the cytoplasm but use it for reactions in mitochondria, chloroplasts, and peroxisomes, implying that these organelles have CoA transporters. A plant peroxisomal CoA transporter is already known, but plant mitochondrial or chloroplastic CoA transporters are not. Mitochondrial CoA transporters belonging to the mitochondrial carrier family, however, have been identified in yeast (Saccharomyces cerevisiae; Leu-5p) and mammals (SLC25A42). Comparative genomic analysis indicated that angiosperms have two distinct homologs of these mitochondrial CoA transporters, whereas nonflowering plants have only one. The homologs from maize (Zea mays; GRMZM2G161299 and GRMZM2G420119) and Arabidopsis (Arabidopsis thaliana; At1g14560 and At4g26180) all complemented the growth defect of the yeast leu5Δ mitochondrial CoA carrier mutant and substantially restored its mitochondrial CoA level, confirming that these proteins have CoA transport activity. Dual-import assays with purified pea (Pisum sativum) mitochondria and chloroplasts, and subcellular localization of green fluorescent protein fusions in transiently transformed tobacco (Nicotiana tabacum) Bright Yellow-2 cells, showed that the maize and Arabidopsis proteins are targeted to mitochondria. Consistent with the ubiquitous importance of CoA, the maize and Arabidopsis mitochondrial CoA transporter genes are expressed at similar levels throughout the plant. These data show that representatives of both monocotyledons and eudicotyledons have twin, mitochondrially located mitochondrial carrier family carriers for CoA. The highly conserved nature of these carriers makes possible their reliable annotation in other angiosperm genomes. PMID:23590975

  18. SCREENING OF HMG CO A REDUCTASE INHIBITOR PRODUCING MARINE ACTINOMYCETES

    SRINU, PHANI BHUSHAN,MOGES, SRILAKSHMI, SANKAR, PRABHAKAR,LAKSHMINARAYANA

    2013-01-01

    The objective of the present study was screening of 3-hydroxy-3- methyl glutaryl Co A (HMG CoA) reductase inhibitor producing marine actinomycetes. A total of 65 morphologically different actinomycetes were screened for HMG CoA reductase inhibitor production in a two stage submerged fermentation and evaluated for HMG CoA reductase inhibitor activity by agar diffusion and thin layer chromatography technique using lovostatin as a control. Among 65 marine Actinomycete strains, only one strain pr...

  19. Deregulated Coenzyme A, Loss of Metabolic Flexibility and Diabetes

    Jackowski, Suzanne; Leonardi, Roberta

    2016-01-01

    Coenzyme A (CoA) is an essential cofactor that is emerging as a global regulator of energy metabolism. Tissue CoA levels are tightly regulated and vary in response to different conditions including nutritional state and diabetes. Recent studies reveal the ability of this cofactor to control the output of key metabolic pathways. CoA regulation is important for the maintenance of metabolic flexibility and glucose homeostasis. PMID:25110012

  20. Pantethine Rescues Phosphopantothenoylcysteine Synthetase and Phosphopantothenoylcysteine Decarboxylase Deficiency in Escherichia coli but Not in Pseudomonas aeruginosa▿†

    Balibar, Carl J.; Hollis-Symynkywicz, Micah F.; Tao, Jianshi

    2011-01-01

    Coenzyme A (CoA) plays a central and essential role in all living organisms. The pathway leading to CoA biosynthesis has been considered an attractive target for developing new antimicrobial agents with novel mechanisms of action. By using an arabinose-regulated expression system, the essentiality of coaBC, a single gene encoding a bifunctional protein catalyzing two consecutive steps in the CoA pathway converting 4′-phosphopantothenate to 4′-phosphopantetheine, was confirmed in Escherichia c...

  1. Main: 1W07 [RPSD[Archive

    Full Text Available 1; Arabidopsis Thaliana Molecule: Acyl-Coa Oxidase; Chain: A, B; Mutation: Yes; Engineered: Yes Oxidoreducta...AGSRHAFEVSDRIARLVASDPVFEKSNRARLSRKELFKSTLRKCAHAFKRIIELRLNEEEAGRLRHFIDQPAYVDLHWGMFVPAI...YLWCSGLPELFAVYVPACTYEGDNVVLQLQVARFLMKTVAQLGSGKVPVGTTAYMGRAAHLLQCRSGVQKAEDWLNPDVVLEAFEARALRMAVTCAKNLSKFENQEQGFQELLADLVEAAI

  2. Changes in the size and composition of intracellular pools of nonesterified coenzyme A and coenzyme A thioesters in aerobic and facultatively anaerobic bacteria.

    Chohnan, S; FURUKAWA, H.; Fujio, T; Nishihara, H.; Takamura, Y

    1997-01-01

    Intracellular levels of three coenzyme A (CoA) molecular species, i.e., nonesterified CoA (CoASH), acetyl-CoA, and malonyl-CoA, in a variety of aerobic and facultatively anaerobic bacteria were analyzed by the acyl-CoA cycling method developed by us. It was demonstrated that there was an intrinsic difference between aerobes and facultative anaerobes in the changes in the size and composition of CoA pools. The CoA pools in the aerobic bacteria hardly changed and were significantly smaller than...

  3. Effect of coarctation of the aorta and bicuspid aortic valve on flow dynamics and turbulence in the aorta using particle image velocimetry

    Keshavarz-Motamed, Zahra; Garcia, Julio; Gaillard, Emmanuel; Maftoon, Nima; Di Labbio, Giuseppe; Cloutier, Guy; Kadem, Lyes

    2014-03-01

    Blood flow in the aorta has been of particular interest from both fluid dynamics and physiology perspectives. Coarctation of the aorta (COA) is a congenital heart disease corresponding to a severe narrowing in the aortic arch. Up to 85 % of patients with COA have a pathological aortic valve, leading to a narrowing at the valve level. The aim of the present work was to advance the state of understanding of flow through a COA to investigate how narrowing in the aorta (COA) affects the characteristics of the velocity field and, in particular, turbulence development. For this purpose, particle image velocimetry measurements were conducted at physiological flow and pressure conditions, with three different aorta configurations: (1) normal case: normal aorta + normal aortic valve; (2) isolated COA: COA (with 75 % reduction in aortic cross-sectional area) + normal aortic valve and (3) complex COA: COA (with 75 % reduction in aortic cross-sectional area) + pathological aortic valve. Viscous shear stress (VSS), representing the physical shear stress, Reynolds shear stress (RSS), representing the turbulent shear stress, and turbulent kinetic energy (TKE), representing the intensity of fluctuations in the fluid flow environment, were calculated for all cases. Results show that, compared with a healthy aorta, the instantaneous velocity streamlines and vortices were deeply changed in the presence of the COA. The normal aorta did not display any regions of elevated VSS, RSS and TKE at any moment of the cardiac cycle. The magnitudes of these parameters were elevated for both isolated COA and complex COA, with their maximum values mainly being located inside the eccentric jet downstream of the COA. However, the presence of a pathologic aortic valve, in complex COA, amplifies VSS (e.g., average absolute peak value in the entire aorta for a total flow of 5 L/min: complex COA: = 36 N/m2; isolated COA = 19 N/m2), RSS (e.g., average peak value in the entire aorta for a total flow of 5

  4. Coenzyme A and its derivatives : renaissance of a textbook classic

    Theodoulou, Frederica L.; Sibon, Ody C. M.; Jackowski, Suzanne; Gout, Ivan

    2014-01-01

    In 1945, Fritz Lipmann discovered a heat-stable cofactor required for many enzyme-catalysed acetylation reactions. He later determined the structure for this acetylation coenzyme, or coenzyme A (CoA), an achievement for which he was awarded the Nobel Prize in 1953. CoA is now firmly embedded in the

  5. Grief-Processing-Based Psychological Intervention for Children Orphaned by AIDS in Central China: A Pilot Study

    Lin, Xiuyun; Fang, Xiaoyi; Chi, Peilian; Li, Xiaoming; Chen, Wenrui; Heath, Melissa Allen

    2014-01-01

    A group of 124 children orphaned by AIDS (COA), who resided in two orphanages funded by the Chinese government, participated in a study investigating the efficacy of a grief-processing-based psychological group intervention. This psychological intervention program was designed to specifically help COA process their grief and reduce their…

  6. Sequence Classification: 389949 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31794460|ref|NP_856953.1| PROBABLE PROPIONYL-COA CARB...OXYLASE BETA CHAIN 5 ACCD5 (PCCASE) (PROPANOYL-COA:CARBON DIOXIDE LIGASE) || http://www.ncbi.nlm.nih.gov/protein/31794460 ...

  7. Sequence Classification: 390462 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31794973|ref|NP_857466.1| PROBABLE PROPIONYL-COA CARB...OXYLASE BETA CHAIN 4 ACCD4 (PCCASE) (PROPANOYL-COA:CARBON DIOXIDE LIGASE) || http://www.ncbi.nlm.nih.gov/protein/31794973 ...

  8. InterProScan Result: CK523618 [KAIKOcDNA[Archive

    Full Text Available CK523618 CK523618_6_ORF1 9340A0F489CFC86C PANTHER PTHR18866 CARBOXYLASE:PYRUVATE/AC...ETYL-COA/PROPIONYL-COA CARBOXYLASE 2.1e-14 T IPR005482 unintegrated Molecular Function: ligase activity (GO:0016874) ...

  9. Sequence Classification: 389173 [

    Full Text Available BLE SUCCINYL-COA:3-KETOACID-COENZYME A TRANSFERASE (ALPHA SUBUNIT) SCOA (3-OXO ACID:CoA TRANSFERASE) (OXCT A...) (SUCCINYL-COA:3-OXOACID-COENZYME A TRANSFERASE) || http://www.ncbi.nlm.nih.gov/protein/31793684 ...

  10. Sequence Classification: 398927 [

    Full Text Available BLE SUCCINYL-COA:3-KETOACID-COENZYME A TRANSFERASE (ALPHA SUBUNIT) SCOA (3-OXO ACID:CoA TRANSFERASE) (OXCT A...) (SUCCINYL-COA:3-OXOACID-COENZYME A TRANSFERASE) || http://www.ncbi.nlm.nih.gov/protein/15609641 ...

  11. 76 FR 78706 - Self-Regulatory Organizations; C2 Options Exchange, Incorporated; Notice of Filing and Immediate...

    2011-12-19

    ... Effectiveness of Proposed Rule Change Related to a Complex Order Auction Feature December 12, 2011. Pursuant to... electronic complex order book (``COB''). Paragraph (c) of Rule 6.13 describes the COA process. Interpretation.... The Exchange is proposing to amend the rule to describe a COA feature for complex orders resting...

  12. The prevalence of type A personality in the children of alcoholics.

    Manning, D T; Balson, P M; Xenakis, S

    1986-01-01

    Three studies are reported which investigate the prevalency of an excess risk of type A personality in the children of alcoholics (COAs). Reports in the clinical literature suggest there is an excess risk of type A in COAs, but this has never been empirically demonstrated. The Matthews Youth Test for Health (MYTH) was administered to nonalcoholic mothers of 46 COAs and 65 matched controls to measure children's type A competitiveness and impatience-aggression. Results were significant only for greater impatience-aggression in COAs. In a second study, 104 COAs and controls matched for age, sex, race, and father's occupational status were rated by military fathers of intact families using MYTH. The results of the first study were not replicated for COAs, and there was no correlation between a father's Jenkins Activity Scale (JAS) score and his child's type A personality. A third study of 70 matched COAs and controls used the Hunter-Wolf A-B Rating scale, a self-rating scale for children and found no significant differences in children's type A personalities based on membership in an alcoholic family, sex, or birth order. It was concluded that the discrepancy between clinical reports and the present data may have been due to misperceptions about successful, hardworking COAs who, particularly in contrast to their more notorious siblings, may be viewed as "workaholics" and improperly labeled as type A personalities. PMID:3521376

  13. Extracellular 4 '-phosphopantetheine is a source for intracellular coenzyme A synthesis

    Srinivasan, Balaji; Baratashvili, Madina; van der Zwaag, Marianne; Kanon, Bart; Colombelli, Cristina; Lambrechts, Roald A.; Schaap, Onno; Nollen, Ellen A.; Podgorsek, Ajda; Kosec, Gregor; Petkovic, Hrvoje; Hayflick, Susan; Tiranti, Valeria; Reijngoud, Dirk-Jan; Grzeschik, Nicola A.; Sibon, Ody C. M.

    2015-01-01

    The metabolic cofactor coenzyme A (CoA) gained renewed attention because of its roles in neurodegeneration, protein acetylation, autophagy and signal transduction. The long-standing dogma is that eukaryotic cells obtain CoA exclusively via the uptake of extracellular precursors, especially vitamin B

  14. Responding to the Charge of Alchemy: Strategies for Evaluating the Reliability and Validity of Costing-Out Research

    Duncombe, William

    2006-01-01

    Reforming school finance systems to support performance standards entails estimating the cost of an adequate education. Cost of adequacy (COA) studies have been done in more than 30 states. Recently Eric Hanushek challenged the legitimacy of COA research, calling it alchemy and pseudoscience. The objectives of this study are to present reliability…

  15. Sequence Classification: 389263 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|31793774|ref|NP_856267.1| PROBABLE FATTY-ACID...-CoA LIGASE FADD9 (FATTY-ACID-COA SYNTHETASE) (FATTY-ACID-COA SYNTHASE) || http://www.ncbi.nlm.nih.gov/protein/31793774 ...

  16. Coagulase gene polymorphisms detected by PCR in Staphylococcus aureus isolated from subclinical bovine mastitis in Turkey.

    Karahan, Murat; Cetinkaya, Burhan

    2007-09-01

    The genetic relatedness of coagulase (coa) positive Staphylococcus aureus isolated from cows with subclinical mastitis in Turkey was investigated by polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) analysis. Among 700 milk samples positive in the California Mastitis Test (CMT), species specific PCR identified 200 (28.6%) isolates as S. aureus and 161 (80.5%) of these isolates were positive for the 3' end of the coa gene by PCR. Most isolates (n=135, 83.9%) produced a single band on coa PCR, with molecular sizes ranging from 500 to 1400bp, whereas a small number of isolates (n=26, 16.1%) yielded two amplification products. Coa RFLP analysis using AluI and Hin6I revealed 23 and 22 band patterns, respectively. The detection of double bands by coa PCR, previously reported in human isolates, suggests that milking personnel can play a role in the transmission of S. aureus. PMID:16901735

  17. Scoliosis in patients with aortic coarctation and patent ductus arteriosus: does standard posterolateral thoracotomy play a role in the development of the lateral curve of the spine?

    Roclawski, Marek; Sabiniewicz, Robert; Potaz, Piotr; Smoczynski, Andrzej; Pankowski, Rafal; Mazurek, Tomasz; Daibo, Bawo

    2009-10-01

    The aim of this study was to determine the influence of lateral thoracotomy on the development of scoliosis in subjects undergoing repair of coarctation of the aorta (CoA) and patent ductus arteriosus (PDA). A group of 133 patients with CoA and PDA was evaluated. Forty-five patients with CoA and 38 with PDA underwent surgery using standard posterolateral thoracotomy (operative group), whereas 12 patients with CoA and 31 with PDA were treated using balloon dilatation and stent or coil implantation (nonoperative group). A spinal examination, together with the evaluation of chest and spinal roentgenograms, was conducted. Among the operated patients, 62% of those with CoA and 55% of those with PDA had clinical scoliosis. In the nonoperated patients, scoliosis was present in only 25% of those with CoA and 16% of those with PDA. Scoliosis ranged between 10 degrees and 42 degrees . In 89% of the operated patients with CoA and 76% of those with PDA the curve was thoracic; in 46% of the CoA group and 57% of the PDA group the curve was left-sided. All curves were right-sided in nonoperated subjects. Scoliosis in the operated group was higher in male than in female subjects (63% vs. 60% in CoA and 86% vs. 37% in PDA). The prevalence of scoliosis after standard posterolateral thoracotomy was significantly higher than after nonsurgical treatment methods in the CoA and PDA groups as well as in the general population. The rate of single thoracic and the rate of left-sided thoracic curves in patients after thoracotomy is higher than in nonoperated patients or in those with idiopathic scoliosis. The rate of scoliosis after thoracotomy is higher in male than female patients, especially after thoracotomy for PDA. PMID:19597861

  18. Induction of Neuron-Specific Degradation of Coenzyme A Models Pantothenate Kinase-Associated Neurodegeneration by Reducing Motor Coordination in Mice.

    Stephanie A Shumar

    Full Text Available Pantothenate kinase-associated neurodegeneration, PKAN, is an inherited disorder characterized by progressive impairment in motor coordination and caused by mutations in PANK2, a human gene that encodes one of four pantothenate kinase (PanK isoforms. PanK initiates the synthesis of coenzyme A (CoA, an essential cofactor that plays a key role in energy metabolism and lipid synthesis. Most of the mutations in PANK2 reduce or abolish the activity of the enzyme. This evidence has led to the hypothesis that lower CoA might be the underlying cause of the neurodegeneration in PKAN patients; however, no mouse model of the disease is currently available to investigate the connection between neuronal CoA levels and neurodegeneration. Indeed, genetic and/or dietary manipulations aimed at reducing whole-body CoA synthesis have not produced a desirable PKAN model, and this has greatly hindered the discovery of a treatment for the disease.Cellular CoA levels are tightly regulated by a balance between synthesis and degradation. CoA degradation is catalyzed by two peroxisomal nudix hydrolases, Nudt7 and Nudt19. In this study we sought to reduce neuronal CoA in mice through the alternative approach of increasing Nudt7-mediated CoA degradation. This was achieved by combining the use of an adeno-associated virus-based expression system with the synapsin (Syn promoter. We show that mice with neuronal overexpression of a cytosolic version of Nudt7 (scAAV9-Syn-Nudt7cyt exhibit a significant decrease in brain CoA levels in conjunction with a reduction in motor coordination. These results strongly support the existence of a link between CoA levels and neuronal function and show that scAAV9-Syn-Nudt7cyt mice can be used to model PKAN.

  19. Pantothenate kinase 1 is required to support the metabolic transition from the fed to the fasted state.

    Roberta Leonardi

    Full Text Available Coenzyme A (CoA biosynthesis is regulated by the pantothenate kinases (PanK, of which there are four active isoforms. The PanK1 isoform is selectively expressed in liver and accounted for 40% of the total PanK activity in this organ. CoA synthesis was limited using a Pank1(-/- knockout mouse model to determine whether the regulation of CoA levels was critical to liver function. The elimination of PanK1 reduced hepatic CoA levels, and fasting triggered a substantial increase in total hepatic CoA in both Pank1(-/- and wild-type mice. The increase in hepatic CoA during fasting was blunted in the Pank1(-/- mouse, and resulted in reduced fatty acid oxidation as evidenced by abnormally high accumulation of long-chain acyl-CoAs, acyl-carnitines, and triglycerides in the form of lipid droplets. The Pank1(-/- mice became hypoglycemic during a fast due to impaired gluconeogenesis, although ketogenesis was normal. These data illustrate the importance of PanK1 and elevated liver CoA levels during fasting to support the metabolic transition from glucose utilization and fatty acid synthesis to gluconeogenesis and fatty acid oxidation. The findings also suggest that PanK1 may be a suitable target for therapeutic intervention in metabolic disorders that feature hyperglycemia and hypertriglyceridemia.

  20. Holographic Weapons Sight as Crew Optical Alignment Sight

    Merancy, Nujoud; Dehmlow, Brian; Brazzel, Jack P.

    2011-01-01

    Crew Optical Alignment Sights (COAS) are used by spacecraft pilots to provide a visual reference to a target spacecraft for lateral relative position during rendezvous and docking operations. NASA s Orion vehicle, which is currently under development, has not included a COAS in favor of automated sensors, but the crew office has requested such a device be added for situational awareness and contingency support. The current Space Shuttle COAS was adopted from Apollo heritage, weighs several pounds, and is no longer available for procurement which would make re-use difficult. In response, a study was conducted to examine the possibility of converting a commercially available weapons sight to a COAS for the Orion spacecraft. The device used in this study was the XPS series Holographic Weapon Sight (HWS) procured from L-3 EOTech. This device was selected because the targeting reticule can subtend several degrees, and display a graphic pattern tailored to rendezvous and docking operations. Evaluations of the COAS were performed in both the Orion low-fidelity mockup and rendezvous simulations in the Reconfigurable Operational Cockpit (ROC) by crewmembers, rendezvous engineering experts, and flight controllers at Johnson Space Center. These evaluations determined that this unit s size and mounting options can support proper operation and that the reticule visual qualities are as good as or better than the current Space Shuttle COAS. The results positively indicate that the device could be used as a functional COAS and supports a low-cost technology conversion solution.

  1. A liquid crystal of ascorbyl palmitate, used as vaccine platform, provides sustained release of antigen and has intrinsic pro-inflammatory and adjuvant activities which are dependent on MyD88 adaptor protein.

    Sánchez Vallecillo, María F; Minguito de la Escalera, María M; Aguirre, María V; Ullio Gamboa, Gabriela V; Palma, Santiago D; González-Cintado, Leticia; Chiodetti, Ana L; Soldano, Germán; Morón, Gabriel; Allemandi, Daniel A; Ardavín, Carlos; Pistoresi-Palencia, María C; Maletto, Belkys A

    2015-09-28

    Modern subunit vaccines require the development of new adjuvant strategies. Recently, we showed that CpG-ODN formulated with a liquid crystal nanostructure formed by self-assembly of 6-O-ascorbyl palmitate (Coa-ASC16) is an attractive system for promoting an antigen-specific immune response to weak antigens. Here, we showed that after subcutaneous injection of mice with near-infrared fluorescent dye-labeled OVA antigen formulated with Coa-ASC16, the dye-OVA was retained at the injection site for a longer period than when soluble dye-OVA was administered. Coa-ASC16 alone elicited a local inflammation, but how this material triggers this response has not been described yet. Although it is known that some materials used as a platform are not immunologically inert, very few studies have directly focused on this topic. In this study, we explored the underlying mechanisms concerning the interaction between Coa-ASC16 and the immune system and we found that the whole inflammatory response elicited by Coa-ASC16 (leukocyte recruitment and IL-1β, IL-6 and IL-12 production) was dependent on the MyD88 protein. TLR2, TLR4, TLR7 and NLRP3-inflammasome signaling were not required for induction of this inflammatory response. Coa-ASC16 induced local release of self-DNA, and in TLR9-deficient mice IL-6 production was absent. In addition, Coa-ASC16 revealed an intrinsic adjuvant activity which was affected by MyD88 and IL-6 absence. Taken together these results indicate that Coa-ASC16 used as a vaccine platform is effective due to the combination of the controlled release of antigen and its intrinsic pro-inflammatory activity. Understanding how Coa-ASC16 works might have significant implications for rational vaccine design. PMID:26188153

  2. Analysis of Leigh syndrome mutations in the yeast SURF1 homolog reveals a new member of the cytochrome oxidase assembly factor family.

    Bestwick, Megan; Jeong, Mi-Young; Khalimonchuk, Oleh; Kim, Hyung; Winge, Dennis R

    2010-09-01

    Three missense SURF1 mutations identified in patients with Leigh syndrome (LS) were evaluated in the yeast homolog Shy1 protein. Introduction of two of the Leigh mutations, F(249)T and Y(344)D, in Shy1 failed to significantly attenuate the function of Shy1 in cytochrome c oxidase (CcO) biogenesis as seen with the human mutations. In contrast, a G(137)E substitution in Shy1 results in a nonfunctional protein conferring a CcO deficiency. The G(137)E Shy1 mutant phenocopied shy1Delta cells in impaired Cox1 hemylation and low mitochondrial copper. A genetic screen for allele-specific suppressors of the G(137)E Shy1 mutant revealed Coa2, Cox10, and a novel factor designated Coa4. Coa2 and Cox10 are previously characterized CcO assembly factors. Coa4 is a twin CX(9)C motif mitochondrial protein localized in the intermembrane space and associated with the inner membrane. Cells lacking Coa4 are depressed in CcO activity but show no impairment in Cox1 maturation or formation of the Shy1-stabilized Cox1 assembly intermediate. To glean insights into the functional role of Coa4 in CcO biogenesis, an unbiased suppressor screen of coa4Delta cells was conducted. Respiratory function of coa4Delta cells was restored by the overexpression of CYC1 encoding cytochrome c. Cyc1 is known to be important at an ill-defined step in the assembly and/or stability of CcO. This new link to Coa4 may begin to further elucidate the role of Cyc1 in CcO biogenesis. PMID:20624914

  3. Production of Coenzyme A by a Mutant of Brevibacterium ammoniagenes Resistant to Oxypantetheine

    Shimizu, Sakayu; Esumi, Akihiko; Komaki, Ryohei; Yamada, Hideaki

    1984-01-01

    For improved production of coenzyme A (CoA), a mutant of Brevibacterium ammoniagenes IFO127071 resistant to oxypantetheine, the corresponding oxygen analog of pantetheine, was obtained. In the mutant, activity of pantothenate kinase (EC 2.7.1.33), the first-step enzyme for the biosynthesis of CoA from pantothenic acid, l-cysteine, and ATP, was about threefold higher than that in the parent strain. As the main regulation mechanism of CoA biosynthesis in this bacterium is negative feedback inhi...

  4. Purification to homogeneity and characterization of acyl coenzyme A:6-aminopenicillanic acid acyltransferase of Penicillium chrysogenum.

    E. Alvarez; Cantoral, J M; Barredo, J L; Díez, B; Martín, J F

    1987-01-01

    The acyl coenzyme A (CoA):6-aminopenicillanic acid (6-APA) acyltransferase of Penicillium chrysogenum AS-P-78 was purified to homogeneity, as concluded by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing. The enzyme is a monomer with a molecular weight of 30,000 +/- 1,000 and a pI of about 5.5. The optimal pH and temperature were 8.0 and 25 degrees C, respectively. This enzyme converts 6-APA into penicillin by using phenylacetyl CoA or phenoxyacetyl CoA as ac...

  5. Trimetazidine therapy prevents obesity-induced cardiomyopathy in mice.

    Ussher, John R; Fillmore, Natasha; Keung, Wendy; Mori, Jun; Beker, Donna L; Wagg, Cory S; Jaswal, Jagdip S; Lopaschuk, Gary D

    2014-08-01

    Obesity is a significant risk factor for the development of cardiovascular disease. Inhibiting fatty acid oxidation has emerged as a novel approach for the treatment of ischemic heart disease. Our aim was to determine whether pharmacologic inhibition of 3-ketoacyl-coenzyme A thiolase (3-KAT), which catalyzes the final step of fatty acid oxidation, could improve obesity-induced cardiomyopathy. A 3-week treatment with the 3-KAT inhibitor trimetazidine prevented obesity-induced reduction in both systolic and diastolic function. Therefore, targeting cardiac fatty acid oxidation may be a novel therapeutic approach to alleviate the growing burden of obesity-related cardiomyopathy. PMID:25064584

  6. Untersuchungen zur Produktion von Vanillin durch Amycolatopsis sp. HR167, Ferulasäurekatabolismus und Etablierung eines Transformationssystems

    Achterholt, S. (Sandra)

    2002-01-01

    Die Arbeit befaßt sich mit dem Gram-positiven Bakterium Amycolatopsis sp. HR167, welcher von der Firma Haarmann und Reimer (Holzminden) für die biotechnologische Produktion von Vanillin aus Ferulasäure eingesetzt wird. Es wurden die an dieser Umsetzung beteiligten Gene (Ferulasäure-CoA-Thiolase und Enoyl-CoA-Hydratase/Aldolase) identifiziert und molekularbiologisch charakterisiert. Desweiteren wurde ein Transformationssystem für den Stamm entwickelt, um Fremd-DNA in den Stamm einzubringen. Hi...

  7. USCG MARPOL Servicing Facilities

    Department of Homeland Security — Datasets containing a listing of U.S. Ports and Terminals holding valid MARPOL Certificates of Adequacy (COAs). U.S. Ports and Terminals are issued Certificates of...

  8. Synthesis and transformations of 4-chromene 4-hydroxy-2-pyran-2-one and 4-chromene 4-hydroxycoumarin conjugates

    H Surya Prakash Rao; Venkata Swamy Tangeti

    2013-07-01

    The reaction of -methyl-4-(methylthio)-3-nitro-4-chromen-2-amine and its derivatives with 4-hydroxy-6-methyl-2-pyran-2-one in EtOH reflux for 5 min furnish 4-hydroxy-6-methyl-3-(2-(methylamino)-3-nitro-4-chromen-4-yl)-2-pyran-2-ones in quantitative yield. By extending EtOH reflux for 2 h, the 4-chromene 4-hydroxy-2-pyranone conjugates get converted into acetoacetyl coumarins. Similar reaction of -methyl-4-(methylthio)-3-nitro-4-chromen-2-amine and its derivatives with 4-hydroxycoumarin in EtOH reflux furnish 4-hydroxy-2'-(methylamino)-3'-nitro-2,4'-3,4'-bichromen-2-ones. In contrast to earlier system, prolonging reflux in EtOH or in -PrOH reflux the product gets transformed into trans-ethyl 3-(2-hydroxyaryl)-4-oxo-3,4-dihydro-2-furo[3,2-c]chromene-2-carboxylates. Thus, facile synthesis and characterization of 4-chromene 4-hydroxy-2-pyrone, 4-chromene 4-hydroxycoumarin conjugates, acetoacetyl coumarins and trans2,3-disubstituted dihydrofuro[3,2-c]coumarins is described.

  9. The Hypolipidemic Activity of Metal Complexes of Amine Carboxyboranes in Rodents

    Hall, Iris H.; Spielvogel, Bernard F.; Sood, Anup; Morse, Karan W.; Norwood III, Verrill M.; Wong, Oi. T.

    1994-01-01

    The metal complexes of amine-carboxyborane including copper, chromium, zinc, calcium amd cobalt were effective hypolipidemic agents lowering both serum cholesterol and triglyceride levels significantly in mice at 8 mg/kg/day, I.P. after 16 days. The agents reduced acetyl CoA synthetase, ATP-dependent citrate lyase, acyl CoA cholesterol acyl transferase, sn¯-glycerol-3-phosphate acyl transferase activities of rat liver and small intestinal mucosa after 14 days treatment. The neutral cholestero...

  10. Biochemical characterization and substrate specificity of jojoba fatty acyl-CoA reductase and jojoba wax synthase.

    Miklaszewska, Magdalena; Banaś, Antoni

    2016-08-01

    Wax esters are used in industry for production of lubricants, pharmaceuticals and cosmetics. The only natural source of wax esters is jojoba oil. A much wider variety of industrial wax esters-containing oils can be generated through genetic engineering. Biotechnological production of tailor-made wax esters requires, however, a detailed substrate specificity of fatty acyl-CoA reductases (FAR) and wax synthases (WS), the two enzymes involved in wax esters synthesis. In this study we have successfully characterized the substrate specificity of jojoba FAR and jojoba WS. The genes encoding both enzymes were expressed heterologously in Saccharomyces cerevisiae and the activity of tested enzymes was confirmed by in vivo studies and in vitro assays using microsomal preparations from transgenic yeast. Jojoba FAR exhibited the highest in vitro activity toward 18:0-CoA followed by 20:1-CoA and 22:1-CoA. The activity toward other 11 tested acyl-CoAs was low or undetectable as with 18:2-CoA and 18:3-CoA. In assays characterizing jojoba WS combinations of 17 fatty alcohols with 14 acyl-CoAs were tested. The enzyme displayed the highest activity toward 14:0-CoA and 16:0-CoA in combination with C16-C20 alcohols as well as toward C18 acyl-CoAs in combination with C12-C16 alcohols. 20:1-CoA was efficiently utilized in combination with most of the tested alcohols. PMID:27297992

  11. Drug: D07474 [KEGG MEDICUS

    Full Text Available D07474 Drug Atorvastatin ... (INN); Lipitor (TN); Sortis (TN) C33H35FN2O5 558.253 558.6398 D07474.gi ... , PLAIN C10AA HMG CoA reductase inhibitors C10AA05 Atorvastatin ... D07474 Atorvastatin ... (INN) USP drug classification ... Agents Dyslipidemics, HMG CoA Reductase Inhibitors Atorvastatin ... D07474 Atorvastatin ... (INN) Target-based classificat ...

  12. In Vitro Enzymatic Synthesis of New Penicillins Containing Keto Acids as Side Chains

    Ferrero, Miguel A.; Reglero, Angel; Martínez-Blanco, Honorina; Fernández-Valverde, Martiniano; Luengo, Jose M.

    1991-01-01

    Seven different penicillins containing α-ketobutyric, β-ketobutyric, γ-ketovaleric, α-ketohexanoic, δ-ketohexanoic, ε-ketoheptanoic, and α-ketooctanoic acids as side chains have been synthesized in vitro by incubating the enzymes phenylacetyl coenzyme A (CoA) ligase from Pseudomonas putida and acyl-CoA:6-aminopenicillanic acid acyltransferase from Penicillium chrysogenum with CoA, ATP, Mg2+, dithiothreitol, 6-aminopenicillanic acid, and the corresponding side chain precursor.

  13. Determination of bacterial meningitis: a retrospective study of 80 cerebrospinal fluid specimens evaluated by four in vitro methods.

    Wasilauskas, B L; Hampton, K D

    1982-01-01

    A total of 80 cerebrospinal fluid specimens were analyzed for bacterial meningitis by four procedures readily available to most laboratories. These tests included routine culturing. Gram staining, countercurrent immunoelectrophoresis, staphylococcal coagglutination (CoA) with laboratory-prepared reagents, and CoA with Pharmacia Diagnostics reagents. A total of 56 specimens were positive for bacterial agents by routine culturing: Gram stain results were positive for 64% of all specimens positi...

  14. Integrated Electroosmotic Perfusion of Tissue with Online Microfluidic Analysis to Track the Metabolism of Cystamine, Pantethine and Coenzyme A

    Wu, Juanfang; Sandberg, Mats; Weber, Stephen G.

    2013-01-01

    We have developed an approach that integrates electroosmotic perfusion of tissue with a substrate-containing solution and online microfluidic analysis of products, in this case thiols. Using this approach we have tracked the metabolism of cystamine, pantethine and CoA in the extracellular space of organotypic hippocampal slice cultures (OHSCs). Currently, little is known about coenzyme A (CoA) biodegradation and even less is known about the regulation and kinetic characteristics for this sequ...

  15. The STM4195 Gene Product (PanS) Transports Coenzyme A Precursors in Salmonella enterica

    Ernst, Dustin C.; Downs, Diana M.

    2015-01-01

    Coenzyme A (CoA) is a ubiquitous coenzyme involved in fundamental metabolic processes. CoA is synthesized from pantothenic acid by a pathway that is largely conserved among bacteria and eukaryotes and consists of five enzymatic steps. While higher organisms, including humans, must scavenge pantothenate from the environment, most bacteria and plants are capable of de novo pantothenate biosynthesis. In Salmonella enterica, precursors to pantothenate can be salvaged, but subsequent intermediates...

  16. Inhibitors of Fatty Acid Synthesis Induce PPAR α -Regulated Fatty Acid β -Oxidative Genes: Synergistic Roles of L-FABP and Glucose

    Huan Huang; McIntosh, Avery L.; Martin, Gregory G.; Petrescu, Anca D.; Landrock, Kerstin K.; Danilo Landrock; Kier, Ann B.; Friedhelm Schroeder

    2013-01-01

    While TOFA (acetyl CoA carboxylase inhibitor) and C75 (fatty acid synthase inhibitor) prevent lipid accumulation by inhibiting fatty acid synthesis, the mechanism of action is not simply accounted for by inhibition of the enzymes alone. Liver fatty acid binding protein (L-FABP), a mediator of long chain fatty acid signaling to peroxisome proliferator-activated receptor-α (PPARα) in the nucleus, was found to bind TOFA and its activated CoA th...

  17. Role of Subcellular Differentiation in Plant Disease Resistance

    Lang, Saara Susanna

    1997-01-01

    3-Hydroxy-3-methylglutaryl CoA reductase (HMGR, EC 1.1.1.34) catalyzes the reaction from hydroxymethylglutaryl CoA to mevalonate in the isoprenoid pathway. In solanaceous plants, one class of endproducts of the pathway are sesquiterpenoid phytoalexins, antibiotic compounds produced by plants in response to pathogens. We are interested in the role of the defense-inducible isoforms of HMGR in phytoalexin production and disease resistance. Transgenic tobacco, ...

  18. Mild coarctation of the aorta: to touch or not to touch the patient?

    Keshavarz-Motamed, Zahra; Randles, Amanda; Rikhtegar Nezami, Farhad; Partida, Ramon; Nakamura, Kenta; Staziaki, Pedro V.; Ghoshhajra, Brian; Bhatt, Ami; Edelman, Elazer R.

    2015-11-01

    Coarctation of the aorta (COA) is an aortic obstruction. A peak-to-peak trans-coarctation pressure gradient (PKdP) of greater than 20 mmHg warns severe COA and the need for interventional/surgical repair. The optimal method and timing of intervention remain uncertain especially for mild COA (PKdP treatment strategies for mild COA may need to be redefined as transcatheter interventions emerge, benefits of such interventions are unclear. We investigated the effects of transcatheter interventions on the aorta and left ventricle (LV) hemodynamics in 11 patients with mild COA using a developed computational fluid dynamics and lumped parameter modeling framework along with particle image velocimetry and clinical measurements. Such interventions can improve aortic hemodynamics to some extent (e.g., time-averaged wall shear stress and kinetic energy were reduced by about 20%). However there is no concomitant effect on the LV hemodynamics (e.g., stroke work and LV pressure were reduced by only less than 4%). Our computational approach can effectively predict clinical conditions. Herein one must question intervention for mild COA, as it has limited utility in reducing myocardial strain.

  19. Contribution of Staphylococcus aureus Coagulases and Clumping Factor A to Abscess Formation in a Rabbit Model of Skin and Soft Tissue Infection

    Malachowa, Natalia; Kobayashi, Scott D.; Porter, Adeline R.; Braughton, Kevin R.; Scott, Dana P.; Gardner, Donald J.; Missiakas, Dominique M.; Schneewind, Olaf; DeLeo, Frank R.

    2016-01-01

    Staphylococcus aureus produces numerous factors that facilitate survival in the human host. S. aureus coagulase (Coa) and von Willebrand factor-binding protein (vWbp) are known to clot plasma through activation of prothrombin and conversion of fibrinogen to fibrin. In addition, S. aureus clumping factor A (ClfA) binds fibrinogen and contributes to platelet aggregation via a fibrinogen- or complement-dependent mechanism. Here, we evaluated the contribution of Coa, vWbp and ClfA to S. aureus pathogenesis in a rabbit model of skin and soft tissue infection. Compared to skin abscesses caused by the Newman wild-type strain, those caused by isogenic coa, vwb, or clfA deletion strains, or a strain deficient in coa and vwb, were significantly smaller following subcutaneous inoculation in rabbits. Unexpectedly, we found that fibrin deposition and abscess capsule formation appear to be independent of S. aureus coagulase activity in the rabbit infection model. Similarities notwithstanding, S. aureus strains deficient in coa and vwb elicited reduced levels of several proinflammatory molecules in human blood in vitro. Although a specific mechanism remains to be determined, we conclude that S. aureus Coa, vWbp and ClfA contribute to abscess formation in rabbits. PMID:27336691

  20. Simulation-based planning for peacekeeping operations: selection of robust plans

    Cekova, Cvetelina; Chandrasekaran, B.; Josephson, John; Pantaleev, Aleksandar

    2006-05-01

    This research is part of a proposed shift in emphasis in decision support from optimality to robustness. Computer simulation is emerging as a useful tool in planning courses of action (COAs). Simulations require domain models, but there is an inevitable gap between models and reality - some aspects of reality are not represented at all, and what is represented may contain errors. As models are aggregated from multiple sources, the decision maker is further insulated from even an awareness of model weaknesses. To realize the full power of computer simluations to support decision making, decision support systems should support the planner in exporing the robustness of COAs in the face of potential weaknesses in simulation models. This paper demonstrates a method of exploring the robustness of a COA with respect to specific model assumptions about whose accuracy the decision maker might have concerns. The domain is that of peacekeeping in a country where three differenct demographic groups co-exist in tension. An external peacekeeping force strives to achieve stability, an improved economy, and a higher degree of democracy in the country. A proposed COA for such a force is simluated multiple times while varying the assumptions. A visual data analysis tool is used to explore COA robustness. The aim is to help the decision maker choose a COA that is likely to be successful even in the face of potential errors in the assumptions in the models.

  1. Peroxisomal beta-oxidation defect with detectable peroxisomes: a case with neonatal onset and progressive course.

    Barth, P G; Wanders, R J; Schutgens, R B; Bleeker-Wagemakers, E M; van Heemstra, D

    1990-07-01

    A progressive demyelinating cerebral disorder is described in a normally-appearing female infant with neonatal seizures, progressive psychomotor deterioration, deafness, retinopathy, peripheral neuropathy and loss of myelin observed on magnetic resonance imaging (MRI) scanning. MRI also showed the absence of macroscopic neocortical dysplasia which is usually found in Zellweger syndrome (ZS). Adrenal cortical function was normal. The patient died at the age of 37 months. Extensive biochemical investigations of peroxisomal functions in the patient revealed an impairment of peroxisomal beta-oxidation resulting in elevated levels of very long (greater than C22) chain fatty acids in plasma and fibroblasts. Moreover, elevated plasma levels of intermediates of bile acid biosynthesis such as tri- and dihydroxycholestanoic acid were found. Other peroxisomal functions were normal. Immunoblotting of the peroxisomal beta-oxidation enzyme proteins in liver from the patient revealed normal responses with antisera against acyl-CoA oxidase, bifunctional protein and thiolase respectively. From these data we conclude that the patient had a deficiency of a single peroxisomal beta-oxidation enzyme at the level of either the bifunctional protein or peroxisomal thiolase with retained immunoreactivity against these enzymes. PMID:2209666

  2. The role of UPF0157 in the folding of M. tuberculosis dephosphocoenzyme A kinase and the regulation of the latter by CTP.

    Guneet Walia

    Full Text Available BACKGROUND: Targeting the biosynthetic pathway of Coenzyme A (CoA for drug development will compromise multiple cellular functions of the tubercular pathogen simultaneously. Structural divergence in the organization of the penultimate and final enzymes of CoA biosynthesis in the host and pathogen and the differences in their regulation mark out the final enzyme, dephosphocoenzyme A kinase (CoaE as a potential drug target. METHODOLOGY/PRINCIPAL FINDINGS: We report here a complete biochemical and biophysical characterization of the M. tuberculosis CoaE, an enzyme essential for the pathogen's survival, elucidating for the first time the interactions of a dephosphocoenzyme A kinase with its substrates, dephosphocoenzyme A and ATP; its product, CoA and an intrinsic yet novel inhibitor, CTP, which helps modulate the enzyme's kinetic capabilities providing interesting insights into the regulation of CoaE activity. We show that the mycobacterial enzyme is almost 21 times more catalytically proficient than its counterparts in other prokaryotes. ITC measurements illustrate that the enzyme follows an ordered mechanism of substrate addition with DCoA as the leading substrate and ATP following in tow. Kinetic and ITC experiments demonstrate that though CTP binds strongly to the enzyme, it is unable to participate in DCoA phosphorylation. We report that CTP actually inhibits the enzyme by decreasing its Vmax. Not surprisingly, a structural homology search for the modeled mycobacterial CoaE picks up cytidylmonophosphate kinases, deoxycytidine kinases, and cytidylate kinases as close homologs. Docking of DCoA and CTP to CoaE shows that both ligands bind at the same site, their interactions being stabilized by 26 and 28 hydrogen bonds respectively. We have also assigned a role for the universal Unknown Protein Family 0157 (UPF0157 domain in the mycobacterial CoaE in the proper folding of the full length enzyme. CONCLUSIONS/SIGNIFICANCE: In view of the evidence

  3. Electrical/thermal transport and electronic structure of the binary cobalt pnictides CoPn2 (Pn = As and Sb)

    We demonstrate the electrical and thermal transport properties of polycrystalline CoPn2 (Pn = As and Sb) between 300 and 900 K. CoAs2 shows semiconducting electrical transport up to 900 K, while CoSb2 exhibits degenerate conduction. Sign inversion of the Seebeck coefficient is observed at ∼310 and ∼400 K for CoAs2 and CoSb2, respectively. Thermal conductivity at 300 K is 11.7 Wm−1K−1 for CoAs2 and 9.4 Wm−1K−1 for CoSb2. The thermoelectric power factor of CoAs2 is ∼10 μWcm−1K−2, although the dimensionless figure of merit is limited to ∼0.1 due to relatively high thermal conductivity. Using electronic structure calculations, the band gap value is calculated to be 0.55 eV for CoAs2 and 0.26 eV for CoSb2

  4. Cyberwar XXI: quantifying the unquantifiable: adaptive AI for next-generation conflict simulations

    Miranda, Joseph; von Kleinsmid, Peter; Zalewski, Tony

    2004-08-01

    The era of the "Revolution in Military Affairs," "4th Generation Warfare" and "Asymmetric War" requires novel approaches to modeling warfare at the operational and strategic level of modern conflict. For example, "What if, in response to our planned actions, the adversary reacts in such-and-such a manner? What will our response be? What are the possible unintended consequences?" Next generation conflict simulation tools are required to help create and test novel courses of action (COA's) in support of real-world operations. Conflict simulations allow non-lethal and cost-effective exploration of the "what-if" of COA development. The challenge has been to develop an automated decision-support software tool which allows competing COA"s to be compared in simulated dynamic environments. Principal Investigator Joseph Miranda's research is based on modeling an integrated military, economic, social, infrastructure and information (PMESII) environment. The main effort was to develop an adaptive AI engine which models agents operating within an operational-strategic conflict environment. This was implemented in Cyberwar XXI - a simulation which models COA selection in a PMESII environment. Within this framework, agents simulate decision-making processes and provide predictive capability of the potential behavior of Command Entities. The 2003 Iraq is the first scenario ready for V&V testing.

  5. Inhibition of 3-Hydroxy-3-methylglutaryl Coenzyme A Reductase (Ex Vivo by Morus indica (Mulberry

    Vanitha Reddy Palvai

    2014-01-01

    Full Text Available Phytochemicals are the bioactive components that contribute to the prevention of cardiovascular and other degenerative diseases. Inhibition of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA reductase would be an effective means of lowering plasma cholesterol in humans. The present study explores the HMG CoA reductase inhibitory effect of extracts from leaves of Morus indica varieties, M5, V1, and S36, compared with the statin, using an ex vivo method. The assay is based on the stoichiometric formation of coenzyme A during the reduction of microsomal HMG CoA to mevalonate. Dechlorophyllised extract of three varieties was studied at 300 µg. The coenzyme A released at the end of assay in control (100.31 nmoles and statins (94.46 nm was higher than the dechlorphyllised extracts of the samples. The coenzyme A released during the reduction of HMG CoA to mevalonate in dechlorophyllised extracts of the samples was as follows: S36 < M5 < V1. The results indicated that the samples were highly effective in inhibiting the enzyme compared to statins (standard drug. The results indicate the role of Morus varieties extracts in modulating the cholesterol metabolism by inhibiting the activity of HMG CoA reductase. These results provide scope for designing in vivo animal studies to confirm their effect.

  6. Chaos optimization algorithms based on chaotic maps with different probability distribution and search speed for global optimization

    Yang, Dixiong; Liu, Zhenjun; Zhou, Jilei

    2014-04-01

    Chaos optimization algorithms (COAs) usually utilize the chaotic map like Logistic map to generate the pseudo-random numbers mapped as the design variables for global optimization. Many existing researches indicated that COA can more easily escape from the local minima than classical stochastic optimization algorithms. This paper reveals the inherent mechanism of high efficiency and superior performance of COA, from a new perspective of both the probability distribution property and search speed of chaotic sequences generated by different chaotic maps. The statistical property and search speed of chaotic sequences are represented by the probability density function (PDF) and the Lyapunov exponent, respectively. Meanwhile, the computational performances of hybrid chaos-BFGS algorithms based on eight one-dimensional chaotic maps with different PDF and Lyapunov exponents are compared, in which BFGS is a quasi-Newton method for local optimization. Moreover, several multimodal benchmark examples illustrate that, the probability distribution property and search speed of chaotic sequences from different chaotic maps significantly affect the global searching capability and optimization efficiency of COA. To achieve the high efficiency of COA, it is recommended to adopt the appropriate chaotic map generating the desired chaotic sequences with uniform or nearly uniform probability distribution and large Lyapunov exponent.

  7. Myocardial hypertrophy and the maturation of fatty acid oxidation in the newborn human heart.

    Yatscoff, Michael A; Jaswal, Jagdip S; Grant, Meghan R; Greenwood, Rachel; Lukat, Trish; Beker, Donna L; Rebeyka, Ivan M; Lopaschuk, Gary D

    2008-12-01

    After birth dramatic decreases in cardiac malonyl CoA levels result in the rapid maturation of fatty acid oxidation. We have previously demonstrated that the decrease in malonyl CoA is due to increased activity of malonyl CoA decarboxylase (MCD), and decreased activity of acetyl CoA carboxylase (ACC), enzymes which degrade and synthesize malonyl CoA, respectively. Decreased ACC activity corresponds to an increase in the activity of 5'-AMP activated protein kinase (AMPK), which phosphorylates and inhibits ACC. These alterations are delayed by myocardial hypertrophy. As rates of fatty acid oxidation can influence the ability of the heart to withstand an ischemic insult, we examined the expression of MCD, ACC, and AMPK in the newborn human heart. Ventricular biopsies were obtained from infants undergoing cardiac surgery. Immunoblot analysis showed a positive correlation between MCD expression and age. In contrast, a negative correlation in both ACC and AMPK expression and age was observed. All ventricular samples displayed some degree of hypertrophy, however, no differences in enzyme expression were found between moderate and severe hypertrophy. This indicates that increased expression of MCD, and the decreased expression of ACC and AMPK are important regulators of the maturation of fatty acid oxidation in the newborn human heart. PMID:18614968

  8. Metabolic annotation of 2-ethylhydracrylic acid.

    Ryan, Robert O

    2015-08-25

    Increased levels of the organic acid, 2-ethylhydracrylic acid (2-EHA) occur in urine of subjects with impaired L(+)-isoleucine metabolism. Chiral intermediates formed during isoleucine degradation are (S) enantiomers. Blockage of (S) pathway flux drives racemization of (2S, 3S) L(+)-isoleucine and its (2S, 3R) stereoisomer, L(+)-alloisoleucine. This non-protein amino acid is metabolized to (R)-2-methylbutyryl CoA via enzymes common to branched chain amino acid degradation. Subsequently, (R) intermediates serve as alternate substrates for three valine metabolic enzymes, generating 2-EHA. Once formed, 2-EHA accumulates because it is poorly recognized by distal valine pathway enzymes. Thus, urinary 2-EHA represents a biomarker of isoleucine pathway defects. 2-EHA levels are also increased in rats exposed to the industrial solvent, ethylene glycol monomethyl ether or the neurotoxin precursor, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. In these cases, a block in (S) pathway isoleucine catabolism occurs at the level of (S)-2-methylbutyryl CoA conversion to tiglyl CoA via inhibition of electron transferring flavoprotein/ubiquinone oxidoreductase dependent reactions. Elevated urinary 2-EHA in propionyl CoA carboxylase deficiency and methylmalonic aciduria results from a buildup of distal intermediates in the (S) pathway of isoleucine degradation. In Barth syndrome and dilated cardiomyopathy with ataxia syndrome, 2-EHA is a byproduct of impeded propionyl CoA entry into the Krebs cycle. PMID:26115894

  9. Electrical/thermal transport and electronic structure of the binary cobalt pnictides CoPn2 (Pn = As and Sb

    Yosuke Goto

    2015-06-01

    Full Text Available We demonstrate the electrical and thermal transport properties of polycrystalline CoPn2 (Pn = As and Sb between 300 and 900 K. CoAs2 shows semiconducting electrical transport up to 900 K, while CoSb2 exhibits degenerate conduction. Sign inversion of the Seebeck coefficient is observed at ∼310 and ∼400 K for CoAs2 and CoSb2, respectively. Thermal conductivity at 300 K is 11.7 Wm−1K−1 for CoAs2 and 9.4 Wm−1K−1 for CoSb2. The thermoelectric power factor of CoAs2 is ∼10 μWcm−1K−2, although the dimensionless figure of merit is limited to ∼0.1 due to relatively high thermal conductivity. Using electronic structure calculations, the band gap value is calculated to be 0.55 eV for CoAs2 and 0.26 eV for CoSb2.

  10. Parallel and four-step synthesis of natural-product-inspired scaffolds through modular assembly and divergent cyclization

    Hiroki Oguri

    2012-06-01

    Full Text Available By emulating the universal biosynthetic strategy, which employs modular assembly and divergent cyclizations, we have developed a four-step synthetic process to yield a collection of natural-product-inspired scaffolds. Modular assembly of building blocks onto a piperidine-based manifold 6, having a carboxylic acid group, was achieved through Ugi condensation, N-acetoacetylation and diazotransfer, leading to cyclization precursors. The rhodium-catalyzed tandem cyclization and divergent cycloaddition gave rise to tetracyclic and hexacyclic scaffolds by the appropriate choice of dipolarophiles installed at modules 3 and 4. A different piperidine-based manifold 15 bearing an amino group was successfully applied to demonstrate the flexibility and scope of the unified four-step process for the generation of structural diversity in the fused scaffolds. Evaluation of in vitro antitrypanosomal activities of the collections and preliminary structure–activity relationship (SAR studies were also undertaken.

  11. Overexpression of human fatty acid transport protein 2/very long chain acyl-CoA synthetase 1 (FATP2/Acsvl1) reveals distinct patterns of trafficking of exogenous fatty acids

    Melton, Elaina M. [Department of Biochemistry, University of Nebraska, Lincoln, NE (United States); Center for Cardiovascular Sciences, Albany Medical College, Albany, NY (United States); Cerny, Ronald L. [Department of Chemistry, University of Nebraska, Lincoln, NE (United States); DiRusso, Concetta C. [Department of Biochemistry, University of Nebraska, Lincoln, NE (United States); Black, Paul N., E-mail: pblack2@unl.edu [Department of Biochemistry, University of Nebraska, Lincoln, NE (United States)

    2013-11-01

    Highlights: •Roles of FATP2 in fatty acid transport/activation contribute to lipid homeostasis. •Use of 13C- and D-labeled fatty acids provide novel insights into FATP2 function. •FATP2-dependent trafficking of FA into phospholipids results in distinctive profiles. •FATP2 functions in the transport and activation pathways for exogenous fatty acids. -- Abstract: In mammals, the fatty acid transport proteins (FATP1 through FATP6) are members of a highly conserved family of proteins, which function in fatty acid transport proceeding through vectorial acylation and in the activation of very long chain fatty acids, branched chain fatty acids and secondary bile acids. FATP1, 2 and 4, for example directly function in fatty acid transport and very long chain fatty acids activation while FATP5 does not function in fatty acid transport but activates secondary bile acids. In the present work, we have used stable isotopically labeled fatty acids differing in carbon length and saturation in cells expressing FATP2 to gain further insights into how this protein functions in fatty acid transport and intracellular fatty acid trafficking. Our previous studies showed the expression of FATP2 modestly increased C16:0-CoA and C20:4-CoA and significantly increased C18:3-CoA and C22:6-CoA after 4 h. The increases in C16:0-CoA and C18:3-CoA suggest FATP2 must necessarily partner with a long chain acyl CoA synthetase (Acsl) to generate C16:0-CoA and C18:3-CoA through vectorial acylation. The very long chain acyl CoA synthetase activity of FATP2 is consistent in the generation of C20:4-CoA and C22:6-CoA coincident with transport from their respective exogenous fatty acids. The trafficking of exogenous fatty acids into phosphatidic acid (PA) and into the major classes of phospholipids (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidyserine (PS)) resulted in distinctive profiles, which changed with the expression of FATP2. The

  12. Clinical Outcome Assessments: Conceptual Foundation-Report of the ISPOR Clinical Outcomes Assessment - Emerging Good Practices for Outcomes Research Task Force.

    Walton, Marc K; Powers, John H; Hobart, Jeremy; Patrick, Donald; Marquis, Patrick; Vamvakas, Spiros; Isaac, Maria; Molsen, Elizabeth; Cano, Stefan; Burke, Laurie B

    2015-09-01

    An outcome assessment, the patient assessment used in an endpoint, is the measuring instrument that provides a rating or score (categorical or continuous) that is intended to represent some aspect of the patient's health status. Outcome assessments are used to define efficacy endpoints when developing a therapy for a disease or condition. Most efficacy endpoints are based on specified clinical assessments of patients. When clinical assessments are used as clinical trial outcomes, they are called clinical outcome assessments (COAs). COAs include any assessment that may be influenced by human choices, judgment, or motivation. COAs must be well-defined and possess adequate measurement properties to demonstrate (directly or indirectly) the benefits of a treatment. In contrast, a biomarker assessment is one that is subject to little, if any, patient motivational or rater judgmental influence. This is the first of two reports by the ISPOR Clinical Outcomes Assessment - Emerging Good Practices for Outcomes Research Task Force. This report provides foundational definitions important for an understanding of COA measurement principles. The foundation provided in this report includes what it means to demonstrate a beneficial effect, how assessments of patients relate to the objective of showing a treatment's benefit, and how these assessments are used in clinical trial endpoints. In addition, this report describes intrinsic attributes of patient assessments and clinical trial factors that can affect the properties of the measurements. These factors should be considered when developing or refining assessments. These considerations will aid investigators designing trials in their choice of using an existing assessment or developing a new outcome assessment. Although the focus of this report is on the development of a new COA to define endpoints in a clinical trial, these principles may be applied more generally. A critical element in appraising or developing a COA is to

  13. Psychological characteristics of children of alcoholics.

    Sher, K J

    1997-01-01

    More than 20 years ago, researchers first noted that children of alcoholics (COA's) appeared to be affected by a variety of problems over the course of their life span. Such problems include fetal alcohol syndrome, which is first manifested in infancy; emotional problems and hyperactivity in childhood; emotional problems and conduct problems in adolescence; and the development of alcoholism in adulthood. Although much has been learned over the ensuing two decades, a number of controversial research areas remain. In particular, debate stems from the fact that despite a common interest in COA's, clinically focused literature and research-focused literature have resulted in two distinct bodies of knowledge. This article reviews important research results, with emphasis on findings generated by the alcohol-research community. Attention also is given to examining the empirical validity of concepts that have been advanced by several influential clinicians from the COA field. PMID:15706777

  14. Creating clinical trial designs that incorporate clinical outcome assessments.

    Gilbert, Mark R; Rubinstein, Lawrence; Lesser, Glenn

    2016-03-01

    Clinical outcome assessments (COAs) are increasingly being used in determining the efficacy of new treatment regimens. This was typified in the recent use of a symptom-based instrument combined with an organ-based measure of response for the approval of ruxolitinib in myelofibrosis. There are challenges in incorporating these COAs into clinical trials, including designating the level of priority, incorporating these measures into a combined or composite endpoint, and dealing with issues related to compliance and interpretation of results accounting for missing data. This article describes the results of a recent panel discussion that attempted to address these issues and provide guidance to the incorporation of COAs into clinical trials, including novel statistical designs, so that the testing of new treatments in patients with cancers of the central nervous system can incorporate these important clinical endpoints. PMID:26989129

  15. Overexpression of human fatty acid transport protein 2/very long chain acyl-CoA synthetase 1 (FATP2/Acsvl1) reveals distinct patterns of trafficking of exogenous fatty acids

    Highlights: •Roles of FATP2 in fatty acid transport/activation contribute to lipid homeostasis. •Use of 13C- and D-labeled fatty acids provide novel insights into FATP2 function. •FATP2-dependent trafficking of FA into phospholipids results in distinctive profiles. •FATP2 functions in the transport and activation pathways for exogenous fatty acids. -- Abstract: In mammals, the fatty acid transport proteins (FATP1 through FATP6) are members of a highly conserved family of proteins, which function in fatty acid transport proceeding through vectorial acylation and in the activation of very long chain fatty acids, branched chain fatty acids and secondary bile acids. FATP1, 2 and 4, for example directly function in fatty acid transport and very long chain fatty acids activation while FATP5 does not function in fatty acid transport but activates secondary bile acids. In the present work, we have used stable isotopically labeled fatty acids differing in carbon length and saturation in cells expressing FATP2 to gain further insights into how this protein functions in fatty acid transport and intracellular fatty acid trafficking. Our previous studies showed the expression of FATP2 modestly increased C16:0-CoA and C20:4-CoA and significantly increased C18:3-CoA and C22:6-CoA after 4 h. The increases in C16:0-CoA and C18:3-CoA suggest FATP2 must necessarily partner with a long chain acyl CoA synthetase (Acsl) to generate C16:0-CoA and C18:3-CoA through vectorial acylation. The very long chain acyl CoA synthetase activity of FATP2 is consistent in the generation of C20:4-CoA and C22:6-CoA coincident with transport from their respective exogenous fatty acids. The trafficking of exogenous fatty acids into phosphatidic acid (PA) and into the major classes of phospholipids (phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidyserine (PS)) resulted in distinctive profiles, which changed with the expression of FATP2. The

  16. AcEST: DK944175 [AcEST

    Full Text Available 51|FADA_ECOLI 3-ketoacyl-CoA thiolase OS=Escherichia coli... 30 9.0 sp|Q9ERQ6|CSPG5_RAT Chondroit...L PRA Sbjct: 213 ETTVEALATLRPAFDPVNGMVTAGTSSALSDGAAAMLVMSESRAHELGLKPRA 265 >sp|Q9ERQ6|CSPG5_RAT Chondroit...e... 34 5.4 tr|B3NTX0|B3NTX0_DROER GG18628 OS=Drosophila erecta GN=GG18628 P... 34 5.4 tr|B4Q0W1|B4Q0W1_DROYA GE16281 OS=Dro...GTAGGGACGATTGCATC ■■Homology search results ■■ - Swiss-Prot (release 56.9) Link to BlastX Result : Swiss-Prot sp_hit..._id Q14586 Definition sp|Q14586|ZN267_HUMAN Zinc finger protein 267 OS=Homo sapiens Align length 78 Score (bit

  17. Uranium determination in zirconium

    The method used for the spectrometric uranium determination with 2-(2-thiolase)-5-diethylaminophenol was modified for its application in the zirconium samples analysis with an uranium content of the 0.1% order. The samples, previously dissolved in nitric acid, were submitted to a separative stage of liquid-liquid extraction, with a trioctylphosphine (TOPO) oxide diluted in cyclohexane. A sodium fluoride aqueous solution was necessary to be aggregated in the spectrometric determination so as to complex the zirconium vestiges, which could be present, originated by the Zr/U high relation of the initial sample. Under the established working conditions, different spectrometric assays, dyes absorption spectra and its uranium complex, complex stability, PH influence determination of the dyes-uranium relation, calculation of the complex's apparent formation constant and its molar absorption, were performed. (Author)

  18. Adjuvant activity of CpG-ODN formulated as a liquid crystal.

    Sánchez Vallecillo, María F; Ullio Gamboa, Gabriela V; Palma, Santiago D; Harman, María F; Chiodetti, Ana L; Morón, Gabriel; Allemandi, Daniel A; Pistoresi-Palencia, María C; Maletto, Belkys A

    2014-03-01

    The adjuvants approved in human vaccine with recombinant/purified antigens induce weak cellular immune response and so the development of new adjuvant strategies is critical. CpG-ODN has successfully been used as an adjuvant (phase I-III clinical trials) but its bioavailability needs to be improved. We investigated the adjuvant ability of CpG-ODN formulated with a liquid crystal nanostructure of 6-O-ascorbyl palmitate (Coa-ASC16). Mice immunized with OVA/CpG-ODN/Coa-ASC16 elicited a potent specific IgG1, IgG2a, Th1 and Th17 cellular response without systemic adverse effects. These responses were superior to those induced by OVA/CpG-ODN (solution of OVA with CpG-ODN) and to those induced by the formulation OVA/CpG-ODN/Al(OH)3. Immunization with OVA/CpG-ODN/Coa-ASC16 resulted in a long-lasting cell-mediated immune response (at least 6.5 months). Furthermore, Coa-ASC16 alone allows a controlled release of CpG-ODN in vitro and induces local inflammatory response, independent of TLR4 signaling, characterized by an influx of neutrophils and Ly6C(high) monocytes and pro-inflammatory cytokines. Remarkably, the adjuvant capacity of CpG-ODN co-injected with Coa-ASC16 (OVA/CpG-ODN plus Coa-ASC16) was similar to the adjuvant activity of OVA/CpG-ODN, supporting the requirement for whole formulation to help CpG-ODN adjuvanticity. These results show the potential of this formulation, opening a new avenue for the development of better vaccines. PMID:24382332

  19. Decreased hepatic contents of coenzyme A molecular species in mice after subchronic mild social defeat stress.

    Kubota, Yoshifumi; Goto, Tatsuhiko; Hagiya, Yuki; Chohnan, Shigeru; Toyoda, Atsushi

    2016-03-01

    Social stress may precipitate psychiatric disorders such as depression, which is related to the occurrence of the metabolic syndrome, including obesity and type 2 diabetes. We have evaluated the effects of social stress on central and peripheral metabolism using a model of depression in mice. In the present study, we focused on coenzyme A (CoA) molecular species [i.e. non-esterified CoA (CoASH), acetyl-CoA and malonyl-CoA] which play important roles in numerous metabolic pathways, and we analyzed changes in expression of these molecules in the hypothalamus and liver of adult male mice (C57BL/6J) subjected to 10 days of subchronic mild social defeat stress (sCSDS) with ICR mice as aggressors. Mice (n = 12) exposed to showed hyperphagia- and polydipsia-like symptoms and increased body weight gain compared with control mice which were not affected by exposure to ICR mice (n = 12). To elucidate the underlying metabolic features in the sCSDS model, acetyl-CoA, malonyl-CoA and CoASH tissue levels were analyzed using the acyl-CoA cycling method. The levels of hypothalamic malonyl-CoA, which decreases feeding behavior, were not influenced by sCSDS. However, sCSDS reduced levels of acetyl-CoA, malonyl-CoA and total CoA (sum of the three CoA molecular species) in the liver. Hence, hyperphagia-like symptoms in sCSDS mice evidently occurred independently of hypothalamic malonyl-CoA, but might consequently lead to down-regulation of hepatic CoA via altered expression of nudix hydrolase 7. Future studies should investigate the molecular mechanism(s) underlying the down-regulation of liver CoA pools in sCSDS mice. PMID:26864137

  20. Coenzyme A disulfide reductase, the primary low molecular weight disulfide reductase from Staphylococcus aureus. Purification and characterization of the native enzyme.

    delCardayre, S B; Stock, K P; Newton, G L; Fahey, R C; Davies, J E

    1998-03-01

    The human pathogen Staphylococcus aureus does not utilize the glutathione thiol/disulfide redox system employed by eukaryotes and many bacteria. Instead, this organism produces CoA as its major low molecular weight thiol. We report the identification and purification of the disulfide reductase component of this thiol/disulfide redox system. Coenzyme A disulfide reductase (CoADR) catalyzes the specific reduction of CoA disulfide by NADPH. CoADR has a pH optimum of 7.5-8.0 and is a dimer of identical subunits of Mr 49,000 each. The visible absorbance spectrum is indicative of a flavoprotein with a lambdamax = 452 nm. The liberated flavin from thermally denatured enzyme was identified as flavin adenine dinucleotide. Steady-state kinetic analysis revealed that CoADR catalyzes the reduction of CoA disulfide by NADPH at pH 7.8 with a Km for NADPH of 2 muM and for CoA disulfide of 11 muM. In addition to CoA disulfide CoADR reduces 4,4'-diphosphopantethine but has no measurable ability to reduce oxidized glutathione, cystine, pantethine, or H2O2. CoADR demonstrates a sequential kinetic mechanism and employs a single active site cysteine residue that forms a stable mixed disulfide with CoA during catalysis. These data suggest that S. aureus employs a thiol/disulfide redox system based on CoA/CoA-disulfide and CoADR, an unorthodox new member of the pyridine nucleotide-disulfide reductase superfamily. PMID:9488707

  1. Bicuspid aortic valve and aortic coarctation are linked to deletion of the X chromosome short arm in Turner syndrome

    Bondy, Carolyn; Bakalov, Vladimir K; Cheng, Clara; Olivieri, Laura; Rosing, Douglas R; Arai, Andrew E

    2013-01-01

    Background Congenital heart disease (CHD) is a cardinal feature of X chromosome monosomy, or Turner syndrome (TS). Haploinsufficiency for gene(s) located on Xp have been implicated in the short stature characteristic of the syndrome, but the chromosomal region related to the CHD phenotype has not been established. Design We used cardiac MRI to diagnose cardiovascular abnormalities in four non-mosaic karyotype groups based on 50-metaphase analyses: 45,X (n=152); 46,X,del(Xp) (n=15); 46,X,del(Xq) (n=4); and 46,X,i(Xq) (n=14) from peripheral blood cells. Results Bicuspid aortic valves (BAV) were found in 52/152 (34%) 45,X study subjects and aortic coarctation (COA) in 19/152 (12.5%). Isolated anomalous pulmonary veins (APV) were detected in 15/152 (10%) for the 45,X study group, and this defect was not correlated with the presence of BAV or COA. BAVs were present in 28.6% of subjects with Xp deletions and COA in 6.7%. APV were not found in subjects with Xp deletions. The most distal break associated with the BAV/COA trait was at cytologic band Xp11.4 and ChrX:41,500 000. One of 14 subjects (7%) with the 46,X,i(Xq) karyotype had a BAV and no cases of COA or APV were found in this group. No cardiovascular defects were found among four patients with Xq deletions. Conclusions The high prevalence of BAV and COA in subjects missing only the X chromosome short arm indicates that haploinsufficiency for Xp genes contributes to abnormal aortic valve and aortic arch development in TS. PMID:23825392

  2. Autotrophic growth: the methyl binding site of CO dehydrogenase in the synthesis of acetyl-CoA

    A pathway in which CO or CO2 and H2 is used as a source of energy and carbon to synthesize acetyl-CoA is used for autotrophic growth of acetogenes, methanogens and some sulfate-reducing bacteria. All enzymes involved in this pathway have been purified from C. thermoaceticum. Five of them: CO dehydrogenase (CODH), corrinoid protein, methyltransferase, CODH disulfide reductase (SSRd) and ferredoxin catalyzed synthesis of acetyl-CoA from methyltetrahydrofolate, CO and CoA. CODH is a central enzyme catalyzing the condensation of CH3, CO and CoA and per se it catalyzes a reversible exchange of CO with acetyl-CoA. Thus, CODH must have binding sites for CH3, CO and CoA. They have succeeded in methylating β subunits of CODH using 14CH3I or 14CH-corrinoid protein, a native donor of the CH3 group in synthesis of acetyl-CoA. With resulting [14CH3]CODH, only SSRd is required for synthesis of [14C]acetyl-CoA from CO and CoA. The kinetic studies show that CH3I is a competitive inhibitor for exchange reaction between CO and acetyl-CoA. Acetaldehyde and acetyl-CoA but not acetic acid and CoA protected CODH against methylation by CH3I. Methyl group bound to CODH is very slowly removed by CO and CoA and acetyl-CoA accelerated this process. These data confirm that CH3 group from CH3I and CH3-corrinoid protein is bound to the methyl binding site of CODH

  3. A Case of Glutaric Aciduria Type I with a Novel Mutation

    Nilgun Uyduran Unal; Deniz Kor; Didem Yucel; Gulen Gul Mert; Neslihan Onenli Mungan

    2013-01-01

    Glutaric aciduria type I is an autosomal recessive inherited disorder caused by the deficiency of glutaryl CoA dehydrogenase. The incidence of the disease is 1/100.000. Glutaryl CoA dehydrogenase gene is located on locus 19p13.2. More than 200 mutations have been described for this gene. Most common mutation in the population is C1240T. Clinical symptoms included neurological regression complications such as loss of sucking and swallowing reflexes choreoathetosis, seizures, rigidity and opist...

  4. Isothermal titration calorimetry with micelles: Thermodynamics of inhibitor binding to carnitine palmitoyltransferase 2 membrane protein ☆

    Perspicace, Samantha; Rufer, Arne C.; Thoma, Ralf; Mueller, Francis; Hennig, Michael; Ceccarelli, Simona; Schulz-Gasch, Tanja; Seelig, Joachim

    2013-01-01

    Carnitine palmitoyl transferase 2 (CPT-2) is a key enzyme in the mitochondrial fatty acid metabolism. The active site is comprised of a Y-shaped tunnel with distinct binding sites for the substrate acylcarnitine and the cofactor CoA. We investigated the thermodynamics of binding of four inhibitors directed against either the CoA or the acylcarnitine binding sites using isothermal titration calorimetry (ITC). CPT-2 is a monotopic membrane protein and was solubilized by β-octylglucoside (β-OG) ...

  5. Detection of Cysticercus antigens and antibodies in cerbrospinal fluid of patients with chronic meningitis Detecção de antígenos e anticorpos de Cysticercus em fluido cerebrospinal de pacientes com meningite crônica

    Subhash Chandra Parija

    2007-10-01

    Full Text Available Chronic meningitism is a less frequent manifestation of neurocysticercosis caused by Taenia solium cysticerci. In the present study we used Co-agglutination (Co-A, a simple and rapid slide agglutination test to detect specific Cysticercus antigen in the 67 cerebrospinal fluid (CSF samples from patients with chronic meningitis of unknown etiology. The results were compared with that of ELISA for detection of antibodies. Among these samples four (5.97% were positive for Cysticercus antigen by Co-A test and six (8.95% were positive for antibodies by ELISA. Two samples were positive by both Co-A and ELISA, two were positive only by Co-A and four were positive only by ELISA. In the present study, although Cysticercus antigen and antibodies were present in CSF samples from eight (11.94% patients, we cannot affirm that all the cases of chronic meningitis are due to cysticercosis, but for any case of chronic meningitis of unknown origin, it would be useful to consider the possibility of cysticercal meningitis.Meningite crônica é manifestação pouco freqüente de neurocisticercose causada por cisticerco de Taenia solium. No presente estudo utilizamos co-aglutinação (Co-A um teste simples e rápido de aglutinação para detectar antígeno específico de Cysticercus nas 67 amostras de fluido cerebrospinal (CSF de pacientes com meningite crônica de etiologia desconhecida. Os resultados foram comparados com os de ELISA para detecção de anticorpos. Dentre estas amostras quatro (5,97% foram positivas para antígenos de Cysticercus pelo teste Co-A e seis (8,95% foram positivas para anticorpos por ELISA. Duas amostras foram positivas por ambos Co-A e ELISA, duas foram positivas somente por Co-A e quatro foram positivas somente por ELISA. No presente estudo embora antígenos e anticorpos de Cysticercus estivessem presentes nas amostras de CSF de oito pacientes (11,94%, não podemos afirmar que todos os casos de meningite crônica sejam devidos

  6. Hypocholesterolemic mechanism of phenolics-enriched extract from Moringa oleifera leaves in HepG2 cell lines

    Peera Tabboon

    2016-04-01

    Full Text Available Previous studies have demonstrated the hypolipidemic activity of Moringa oleifera (MO leaves via lowering serum levels of cholesterol, but the mechanism of action is unknown. In this study, we demonstrated the hypocholesterolemic mechanism of a phenolics-enriched extract of Moringa oleifera leaf (PMO in HepG2 cells. When compared to the control treatment, PMO significantly decreased total intracellular cholesterol, inhibited the activity of HMG CoA reductase in a dosedependent manner and enhanced LDL receptor binding activity. Moreover, PMO also significantly increased the genetic expressions of HMG CoA reductase and LDL receptor.

  7. Model for the Production of CO Cameron band emission in Comet 1P/Halley

    Raghuram, Susarla; Bhardwaj, Anil

    2012-01-01

    The abundance of CO2 in comets has been derived using CO Cameron band (a3pi --> X1Sigma+) emission assuming that photodissociative excitation of CO2 is the main production process of CO(a3pi). On comet 1P/Halley the Cameron (1-0) band has been observed by International Ultraviolet Explorer (IUE) on several days in March 1986. A coupled chemistry-emission model is developed for comet 1P/Halley to assess the importance of various production and loss mechanisms of CO(a3pi) and to calculate the i...

  8. Structural studies on the enzymatic units of the peroxisomal multifunctional enzyme type 2 (MFE-2)

    Koski, K.

    2004-01-01

    Abstract Multifunctional enzyme type 2 (MFE-2) is a peroxisomal enzyme participating in the breakdown of fatty acids in eukaryotes. Depending on the organism, MFE-2 is composed of two to four functional units, out of which the two enzymatic ones, 2-enoyl-coenzyme A (CoA) hydratase 2 and (3R)-hydroxyacyl-CoA dehydrogenase, are found in the all MFE-2s. These units are responsible for the catalysis of the second and third steps of the peroxisomal β-oxidation of various CoA thioesters of fatty...

  9. Insight into cofactor recognition in arylamine N-acetyltransferase enzymes

    Xu, Ximing; Li de la Sierra-Gallay, Inés; Kubiak, Xavier Jean Philippe;

    2015-01-01

    Bacillus anthracis NAT1 and Homo sapiens NAT2. Therefore, in contrast to previous data, this study shows that different orthologous NATs can bind their cofactors in a similar way, suggesting that the mode of binding CoA in this family of enzymes is less diverse than previously thought. Moreover, it...

  10. 75 FR 19827 - Acquisition Regulation Rewrite

    2010-04-15

    ... Liability Act CFR Code of Federal Regulations CIO Chief Information Officer CO Contracting Officer COA... suspected antitrust violations. Subpart 1403.4--Contingent Fees 1403.405 Misrepresentations or violations of the Covenant Against Contingent Fees. Subpart 1403.5--Other Improper Business Practices...

  11. GenBank blastx search result: AK288212 [KOME

    Full Text Available AK288212 J090009P04 AY899214.1 AY899214 Streptomyces aizunensis strain NRRL B-11277 glycosyltran ... yl transferase, membrane protein, ABC transporter, sugar ... dehydratase/epimerase, sugar ... epimerase, sugar ... nucl ... eotidyltransferase, sugar ... dehydratase/epimerase, thioesterase, acyl CoA liga ...

  12. Modeling SOA formation from the oxidation of intermediate volatility n-alkanes

    J. Lee-Taylor

    2012-06-01

    Full Text Available The chemical mechanism leading to SOA formation and ageing is expected to be a multigenerational process, i.e. a successive formation of organic compounds with higher oxidation degree and lower vapor pressure. This process is here investigated with the explicit oxidation model GECKO-A (Generator of Explicit Chemistry and Kinetics of Organics in the Atmosphere. Gas phase oxidation schemes are generated for the C8–C24 series of n-alkanes. Simulations are conducted to explore the time evolution of organic compounds and the behavior of secondary organic aerosol (SOA formation for various preexisting organic aerosol concentration (COA. As expected, simulation results show that (i SOA yield increases with the carbon chain length of the parent hydrocarbon, (ii SOA yield decreases with decreasing COA, (iii SOA production rates increase with increasing COA and (iv the number of oxidation steps (i.e. generations needed to describe SOA formation and evolution grows when COA decreases. The simulated oxidative trajectories are examined in a two dimensional space defined by the mean carbon oxidation state and the volatility. Most SOA contributors are not oxidized enough to be categorized as highly oxygenated organic aerosols (OOA but reduced enough to be categorized as hydrocarbon like organic aerosols (HOA, suggesting that OOA may underestimate SOA. Results show that the model is unable to produce highly oxygenated aerosols (OOA with large yields. The limitations of the model are discussed.

  13. Win-Win Trade

    NI YANSHUO

    2011-01-01

    On May 27,a total of 210 orphans in the three states around Abuja,capital of Nigeria,went to a summer camp to celebrate the country's Children's Day.Huawei Technologies Co.,a leading global information and communications technology solutions provider from China,sponsored the event.

  14. Win-Win Trade

    2011-01-01

    China and Afrca find new ways to drive mutual development On May 27,a total of 210 orphans in the three states around Abuja,capital of Nigeria,went to a summer camp to celebrate the country’s Children’s Day. Huawei Technologies Co.,a leading global information and communications technology solutions provider from China,sponsored the event.

  15. Adding Extra Value

    NiYanshuo

    2011-01-01

    A total of 210 orphans in the three states around Abuja,capital of Nigeria,went to a summer camp to celebrate the country's Children's Day on May 27.Huawei Tech nologies Co.,a leading global informa tion and communications technology solutions provider from China,sponsored the event.

  16. CCoAOMT down-regulation activates anthocyanin biosynthesis in petunia

    Shaipulah, N.F.M.; Muhlemann, Joëlle K.; Woodworth, Benjamin D.; Moerkercke, Van Alex; Verdonk, J.C.; Ramirez, A.A.; Haring, Michel A.; Dudareva, Natalia; Schuurink, Robert C.

    2016-01-01

    Anthocyanins and volatile phenylpropenes (isoeugenol and eugenol) in petunia (Petunia hybrida) flowers have the precursor 4-coumaryl coenzyme A (CoA) in common. These phenolics are produced at different stages during flower development. Anthocyanins are synthesized during early stages of flower d

  17. Acyl-CoA synthetase activity links wild-type but not mutant a-Synuclein to brain arachidonate metabolism

    Golovko, Mikhail; Rosenberger, Thad; Færgeman, Nils J.;

    2006-01-01

    an established steady-state kinetic model. Liver was used as a negative control, and no changes were observed between groups. In Snca-/- brains, there was a marked reduction in 20:4n-6-CoA mass and in microsomal acyl-CoA synthetase (Acsl) activity toward 20:4n-6. Microsomal Acsl activity was...

  18. Drosophila phosphopantothenoylcysteine synthetase is required for tissue morphogenesis during oogenesis

    Bosveld, Floris; Rana, Anil; Lemstra - Wierenga, Willemina; Kampinga, Harm; Sibon, Ody

    2008-01-01

    Background: Coenzyme A (CoA) is an essential metabolite, synthesized from vitamin B5 by the subsequent action of five enzymes: PANK, PPCS, PPCDC, PPAT and DPCK. Mutations in Drosophila dPPCS disrupt female fecundity and in this study we analyzed the female sterile phenotype of dPPCS mutants in detai

  19. A Dual-Band Coaxial Waveguide Mode Converter for High-Power Microwave Applications

    A dual-band coaxial waveguide mode converter is investigated. In the converter, the TEM mode (Coa.TEM) and TM01 circular waveguide (Cir.TM01) mode are transformed simultaneously into TE11 coaxial waveguide (Coa.TE11) mode and TE11 circular waveguide (Cir.TE11) mode, respectively. The optimized geometrical dimensions are achieved by employing the mode coupling theory. A mode converter at 1.3 GHz and 5.0 GHz is designed, and conversion efficiencies of Coa.TEM-to-Coa.TE11 and Cir.TM01-to-Cir.TE11 are 99.88% and 99.70% at central frequency, respectively. Over the frequency ranges 1.15–1.51 GHz and 4.87–5.19 GHz, the conversion efficiency exceeds 90%. A good agreement between theoretical calculations and computer simulations is observed, demonstrating the feasibility of the dual-band mode converter. (cross-disciplinary physics and related areas of science and technology)

  20. Sequence Classification: 182868 [

    Full Text Available TMB Non-TMH Non-TMB TMB Non-TMB Non-TMB >gi|17987345|ref|NP_539979.1| BIOTIN CARBOX...YL CARRIER PROTEIN OF ACETYL-COA CARBOXYLASE || http://www.ncbi.nlm.nih.gov/protein/17987345 ...

  1. Sequence Classification: 565760 [

    Full Text Available TMB Non-TMH Non-TMB TMB Non-TMB Non-TMB >gi|15965073|ref|NP_385426.1| PROBABLE BIOTIN CARB...OXYL CARRIER PROTEIN OF ACETYL-COA CARBOXYLASE (BCCP) || http://www.ncbi.nlm.nih.gov/protein/15965073 ...

  2. Sequence Classification: 512243 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|17547505|ref|NP_520907.1| PROBABLE BIOTIN CARB...OXYL CARRIER PROTEIN OF ACETYL-COA CARBOXYLASE (BCCP) || http://www.ncbi.nlm.nih.gov/protein/17547505 ...

  3. Sequence Classification: 400246 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|57117158|ref|NP_218316.2| PROBABLE PROPIONYL-CoA CARB...OXYLASE BETA CHAIN 4 ACCD4 (PCCASE) (PROPANOYL-COA:CARBON DIOXIDE LIGASE) || http://www.ncbi.nlm.nih.gov/protein/57117158 ...

  4. Sequence Classification: 399719 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|15610416|ref|NP_217797.1| PROBABLE PROPIONYL-CoA CARB...OXYLASE BETA CHAIN 5 ACCD5 (PCCASE) (PROPANOYL-COA:CARBON DIOXIDE LIGASE) || http://www.ncbi.nlm.nih.gov/protein/15610416 ...

  5. Sequence Classification: 697789 [

    Full Text Available Non-TMB Non-TMH Non-TMB Non-TMB Non-TMB Non-TMB >gi|34557455|ref|NP_907270.1| PUTATIVE BIOTIN CARB...OXYL CARRIER PROTEIN OF ACETYL-COA CARBOXYLASE || http://www.ncbi.nlm.nih.gov/protein/34557455 ...

  6. Arabidopsis CDS blastp result: AK241568 [KOME

    Full Text Available AK241568 J065179E12 At5g22500.1 68418.m02626 acyl CoA reductase, putative / male -sterility prote ... nensis] GI:5020215; contains Pfam profile PF03015: Male ... sterility protein; identical to cDNA male ... sterilit ...

  7. Arabidopsis CDS blastp result: AK065894 [KOME

    Full Text Available AK065894 J013044F22 At5g22500.1 acyl CoA reductase, putative / male -sterility protein, putative ... nensis] GI:5020215; contains Pfam profile PF03015: Male ... sterility protein; identical to cDNA male ... sterilit ...

  8. Arabidopsis CDS blastp result: AK071956 [KOME

    Full Text Available AK071956 J013084H10 At5g22500.1 acyl CoA reductase, putative / male -sterility protein, putative ... nensis] GI:5020215; contains Pfam profile PF03015: Male ... sterility protein; identical to cDNA male ... sterilit ...

  9. Arabidopsis CDS blastp result: AK069659 [KOME

    Full Text Available AK069659 J023028D15 At5g22500.1 acyl CoA reductase, putative / male -sterility protein, putative ... nensis] GI:5020215; contains Pfam profile PF03015: Male ... sterility protein; identical to cDNA male ... sterilit ...

  10. Arabidopsis CDS blastp result: AK242888 [KOME

    Full Text Available AK242888 J090079L06 At5g22500.1 68418.m02626 acyl CoA reductase, putative / male -sterility prote ... nensis] GI:5020215; contains Pfam profile PF03015: Male ... sterility protein; identical to cDNA male ... sterilit ...