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1
Grünig, Andreas Paul. « Acetyl-CoA : L-Glutamat N-Acetyl-Transferase / ». [S.l : s.n.], 1985. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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2
Babka, Heather Leigh. « Acetyl-CoA in plant biology ». [Ames, Iowa : Iowa State University], 2009. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3389084.
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3
Atalay, Aycin. « N-acetyl Transferase (nat1& ». Master's thesis, METU, 2007. http://etd.lib.metu.edu.tr/upload/2/12607767/index.pdf.
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Breast cancer is the most frequent malignancy among women, especially in Western societies. Highly penetrant genes such as BRCA1 and BRCA2, together with the reproductive history can constitute only 30% of the cause, so there should be other common genes, which may play a role in breast carcinogenesis according to one's lifestyle. In our case, the effect of N-acetyl transferases (NAT1, NAT2) and glutathione-S transferases (GSTM1&
GSTT1) were investigated, since variations in these genes may alter their enzymatic activity and therefore their capacity to biotransform xenobiotic compounds. To evaluate the potential association between NAT1, NAT2, GSTM1 and GSTT1 genotypes and development of breast cancer, a hospital based case-control study was conducted in a Turkish study population consisting of 37 histologically confirmed incident breast cancer cases and 34 control subjects with no present or previous history of cancer. The only recognizable difference between case and control groups is the percentage of GSTM1 deletion, 67.6% and 44.1% respectively (p=0.047). The frequency of rapid NAT2 acetylator genotype is 44.4% in cases and 23.5% in controls. Especially, women with NAT2 rapid acetylator and GSTM1 null genotypes were at the elevated risk (OR, 3.8
CI, 0.9-15.4). NAT1 rapid acetylator genotype showed no association with breast cancer. These results suggest that GSTM1 null genotype is a susceptibility factor for breast cancer, particularly in the presence of NAT2 rapid acetylator genotype.
4
Sheridan, Rose Mary. « Acetyl CoA metabolism in Candida albicans ». Thesis, University of Hull, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241601.
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Anconi, Glasiela Lemos. « Aplicação de peptídeos em cosméticos : desenvolvimento de formulações, estabilidade e eficácia ». Universidade de São Paulo, 2008. http://www.teses.usp.br/teses/disponiveis/60/60137/tde-31032009-144332/.
Texte intégralRésumé :
O objetivo desta pesquisa foi o desenvolvimento, avaliação da estabilidade e da eficácia de formulações cosméticas contendo acetil hexapeptídeo-3 (AHP) ou acetil tetrapeptídeo-5 (ATP) ou mistura de di e tripeptídeos (DTP). Para tal, foram desenvolvidas 6 formulações à base hidroxietilcelulose (HEC), metilfenil polissiloxano (MFP) e álcool batílico e lecitina de soja (ABL) (F1), ou de HEC, MFP, ésteres de polietilenoglicol com cadeia alquílica com 12 a 20 carbonos (EP) (F2), ou de polímero de acrilatos (PA), MFP e ABL (F3) ou de PA, MFP e EP (F4), ou de HEC e MFP (F5) ou de PA e MFP (F6), contendo ou não (veículo) 10% de AHP, ou 10% de ATP ou 4% de DTP, as quais foram submetidas a um estudo de estabilidade física por determinação da reologia e a uma avaliação sensorial. Para o estudo de eficácia dos peptídeos objeto de estudo as formulações foram aplicadas nos antebraços, na face, na região dos olhos e da boca de 60 voluntárias, sendo realizadas medidas do conteúdo aquoso do estrato córneo, da perda de água transepidérmica (TEWL), do micro-relevo cutâneo e das propriedades mecânicas da pele (anisotropia), antes (basal), após 2 horas da aplicação única (efeitos imediatos) e após 15 e 30 dias de uso contínuo (efeitos a longo prazo) das formulações. Os dados foram analisados estatisticamente pelo teste paramétrico análise de variância. Nos testes de estabilidade física, as formulações de nos 1, 2 e 5 foram consideradas as mais estáveis e as formulações de nº 5 e 6 foram as que apresentaram melhor sensorial, sendo, portanto, selecionada a formulação de nº 5 como veículo para os estudos de eficácia. Na avaliação dos efeitos imediatos na pele, observou-se que as formulações estudadas proporcionaram um aumento significativo no conteúdo aquoso do estrato córneo dos antebraços, enquanto que, somente as formulações acrescidas dos peptídeos provocaram um aumento significativo neste conteúdo na face. Em relação ao micro-relevo cutâneo, as formulações contendo ou não os peptídeos provocaram uma redução do parâmetro Ser (aspereza da pele) e Rt (rugosidade) nos antebraços e a formulação contendo DTP provocou um efeito imediato significativo no parâmetro Sesm (textura da pele). Na avaliação dos efeitos a longo prazo, as formulações ocasionaram uma diminuição significativa na TEWL e as acrescidas dos peptídeos objetos de estudo proporcionaram um aumento significativo no conteúdo aquoso do estrato córneo na região dos olhos, enquanto que nos antebraços e na região da boca todas as formulações acrescidas ou não dos peptídeos ocasionaram um aumento nesse parâmetro. Em relação ao micro-relevo cutâneo, a aplicação das formulações contendo os peptídeos, na região da boca, provocou um aumento significativo nos valores de Sesm. A aplicação das formulações contendo os peptídeos objeto de estudo, nos antebraços ocasionou uma diminuição significativa da anisotropia da pele. A formulação nº 5 contendo os peptídeos objeto de estudo, apresentou efeitos imediatos na hidratação, aspereza, rugosidade e textura da pele e, efeitos a longo prazo, na hidratação, textura e anisotropia da pele, mostrando a importância do emprego destes peptídeos em produtos cosméticos com finalidades hidratantes e antienvelhecimento.The aim of this study was the development, evaluation of the stability and the efficacy of cosmetic formulations containing acetyl hexapeptide-3 (AHP), or acetyl tetrapeptide-5 (ATP) or mixture of di- and peptides (DTP). For this purpose the 6 following formulations (F) were developed: F1- containing hydroxyethyl cellulose (HEC), methylphenyl polysiloxane (MPPS), batyl alcohol, and lecithin (BAL); F2- HEC, MPPS and C12-C20 PEG-8 alkyl ester (AE); F3- acrylate copolymer (AC), MPPS and BAL; F4- AC, MPPS and AE; F5- HEC and MPPS and F6- AC and MPPS, which were supplemented or not (vehicle) with 10% of AHP or 10% of ATP or 4% of DTP and submitted to the evaluation of physical stability by the determination of the rheologic behavior and also to the sensorial analysis. For clinical efficacy studies, formulations were applied to the volar forearm and to the face skin (eye corner and cheek region), of 60 female volunteers. Skin conditions in terms of skin moisture, transepidermal water loss (TEWL), skin mechanical properties (anisotropy) and skin microrelief, before and after 2 hours (immediate effects) and after 15 and 30-day period of daily application (long term effects). Results obtained were statistically analyzed using the ANOVA parametric test. In the rheological study, the formulations number 1, 2, and 5 were considered more stable than the others. Moreover, the formulations number 5 and 6 showed the best sensorial attributes, and for this reason the formulation number 5 was selected for the efficacy study. The evaluation of immediate effects of formulations showed that the application of the formulations studied in the volar forearm increased the water content of the stratum corneum, while only the formulations containing the peptides provoked an increased in this content, when face skin was analyzed. When the volar forearm skin microrelief was analyzed, the application of all the formulations studied provoked a significant decrease in skin roughness (Ser) and depth of roughness (Rt), furthermore only the formulation supplemented with the DTP showed a significant increase in the skin smoothness (Sesm). In the evaluation of long term effects, all formulations provoked a significant reduction in TEWL values and the formulations containing the peptides studied provoked a significant increase in the water content of the stratum corneum of eye corner; when the volar forearms and the cheek region were analyzed, all the formulations containing or not the peptides studied, provoked an increase in this parameter. When the skin microrelief was analyzed, only the formulation supplemented with AHP or ATP or DTP, provoked a significant increase in the skin smoothness (Sesm), when applied in the cheek region. The application of formulations containing the peptides studied in the volar forearms provoked a significant decrease in the skin anisotropy. The formulation nº 5 (F5) containing the peptides studied, showed immediate effects on skin hydration, roughness and smoothness, and also long-term effects on skin hydration, smoothness and mechanical properties, which demonstrated the importance of the use of these peptides in cosmetic formulations with hydration and anti-aging purposes.
6
Khew-Goodall, Yee Sim. « Pyruvate carboxylase : its interactions with acetyl CoA / ». Title page, table of contents and summary only, 1985. http://web4.library.adelaide.edu.au/theses/09PH/09phk454.pdf.
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7
Evans, Michael R. « Labeled mimics of N-Acetyl-D-Fucosamine / ». Connect to resource online, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1210527108.
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Watkins, Richard William. « Assimilation of acetyl-CoA by methylotrophic bacteria ». Thesis, Cranfield University, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278721.
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Evans, Michael Ryan. « Labeled Mimics of N-Acetyl-D-Fucosamine ». Youngstown State University / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ysu1210527108.
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10
Quayle, Katherine Amanda. « Regulation of rat liver acetyl CoA carboxylase ». Thesis, University of British Columbia, 1986. http://hdl.handle.net/2429/26028.
Texte intégralRésumé :
Acetyl-CoA carboxylase was purified 750-fold from rat liver cytosol using a modified purification procedure involving high speed ultracentrifugation, sucrose density step gradients, ion-exchange chromatography and avidin-sepharose affinity chromatography. The purified preparation had a specific activity of about 2 U/mg protein and a Km of 80uM for acetyl-CoA. Silver stain of the sample separated by denaturing polyacrylamide gel electrophoresis indicated 95% of the protein migrates as a single protein band with subunit Mr approximately 230Kd. There is approximately 2% contamination of low molecular mass material and 3-5% of the protein runs as a minor band of 240Kd. As the major protein band co-migrates on SDS-po1yacry1 amide gels with immunoprecipitated acetyl-CoA carboxylase from a fresh rat epididymal fat pad tissue extract, it appears that the 240Kd band in the rat liver sample may be a pre-form of the enzyme which undergoes post-translational modification to the mature form of the enzyme.
Despite appearing almost homogeneous after silver-stain, the purified enzyme preparation still contains both cyclic AMP-independent and cyclic AMP-dependent protein kinase activity, the former causing incorporation of 0.1mol Pi/mol acetyl-CoA carboxylase subunit/hr, and the latter causing incorporation of 0.5mol Pi/mol subunit/hr. Addition of specific inhibitor to cyclic AMP-dependent protein kinase effectively blocks all cyclic AMP-dependent protein kinase activity. The cyclic AMP-independent
protein kinase activity co-purifying with acetyl-CoA carboxylase phosphorylates the "control sites" as demonstrated by 2 -dimensional peptide analysis of radioactively labelled ACC. This phosphorylation has no apparent effect on enzyme activity. Phosphorylation by cyclic AMP-dependent protein kinase increases phosphorylation of the control sites and also results in incorporation of [32p] into the two A peptides and one of the B group of phosphopeptides. Neither of these endogenous protein kinase activities cause incorporation of the label into the insulin responsive site of acetyl-CoA carboxylase.
At least 90% of the cyclic AMP-independent protein kinase activity (assayed using ACC as substrate) in the rat liver cytosol co-purifies with acetyl-CoA carboxylase upon sucrose density gradient centrifugation. Under the conditions described, approximately 90% of this protein kinase activity is separated from ACC by DEAE-ce11ulose chromatography, eluting with the other unbound protein from this column. 2-dimensiona1 tryptic peptide analysis of acetyl-CoA carboxylase phosphorylated by this protein kinase fraction increases incorporation of [32p] mainly into the control sites. Further fractionation of this sample however does not reveal increased I site phosphorylation. Protein kinase activity eluted together with ACC (at high salt) from DEAE-cellulose appeared to lead mainly to phosphorylation of the B group of peptides. However, in this case further fractionation of the DEAE-HS fraction on casein-sepharose produces a protein kinase fraction (eluted at 0.5M KC1) which brings about phosphorylation of the insulin-directed site of
acetyl-CoA carboxylase. Thus a cyclic AMP-independent protein kinase activity which phosphorylates acetyl-CoA carboxylase at an insulin responsive site, has been partially purified from rat liver cytosol. We are therefore in a position to explore the effects of insulin-directed phosphorylation on the activity of acetyl-CoA carboxylase.Medicine, Faculty of
Biochemistry and Molecular Biology, Department of
Graduate
11
Quayle, Katherine Amanda. « Mechanisms of regulation of acetyl-CoA carboxylase ». Thesis, University of British Columbia, 1990. http://hdl.handle.net/2429/30657.
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One of the major physiological responses to insulin secretion is the activation of lipogenesis in target tissues (principally fat and liver). As acetyl-CoA carboxylase (ACC) is the rate limiting enzyme in fatty acid synthesis, the mechanisms involved in the short term regulation of this enzyme represent a pertinent model system for determining elements involved in amplification of the signals produced in response to stimulation of cells with lipogenic and counter regulatory hormones. The regulation of mammalian ACC by hormones is a complex phenomenon involving interplay between allosteric and covalent mechanisms. While the effects of adrenaline and glucagon are well characterised, the mechanism of regulation by insulin has still to be defined and formed the focus for the work presented in this thesis.
To study the role of phosphorylation in the response of ACC to insulin, the site-specific phosphorylation of the enzyme observed following exposure of intact cells to insulin has been reproduced in vitro. These studies for the first time describe the conditions required to achieve distribution of [³²P] in vitro among sites of acetyl-CoA carboxylase, very similar to that seen after hormone treatment of intact cells and employing endogenous polyamine-sensitive kinase(s). No corresponding increase in catalytic activity was detected following phosphorylation, in vitro, of insulin directed phosphorylation sites on purified rat liver acetyl-CoA carboxylase in these studies. Subsequently, ACC was phosphorylated by an exogenous protein kinase from maturation activated sea-star oocytes which led to high stoichiometric incorporation of ³²P into the unique site (I-site) phosphorylated in intact cells in
response to insulin (0.3 mol phosphate / mol 240,000 kD subunit). Again no change in ACC activity was observed following I-site phosphorylation. The peptide containing the I-site was separated from other tryptic phosphopeptides by reverse phase HPLC and then sequenced. Phosphorylation of serine 1186 was determined to be the major phosphorylation site of ACC in response to insulin. The amino acid sequence corresponding to the peptide containing Ser 1186 is located in the putative "hinge" region of ACQ which is some 300 amino acids towards the C-terminal of the biotin binding site (Lys-784).
Subsequent re-evaluation of the kinetic properties of acetyl-CoA carboxylase during purification has led to the identification of a fraction containing low Mr inhibitor(s) and an apparently novel protein activator present in rat liver. Affinity purified rat liver acetyl-CoA carboxylase can be activated 2-3 fold at physiological citrate concentrations (0.1-0.5mM) by the addition of the heat and pro tease-sensitive cytosolic protein. The ACC activator has been extensively purified (though not yet to homogeneity) from a 100,000 g supernatant fractions from rat liver extract, by a combination of ammonium sulphate precipitation, ion-exchange chromatography and gel filtration. From these results we concluded that the activator is a protein and the native molecular weight in solution is estimated to be approximately 75 kDaltons.
A popular hypothesis regarding the short term regulation of ACC involves a phosphorylation-dephosphorylation mechanism resulting in inhibition and activation respectively. A number of experiments have been carried out in order to test the hypothesis that the activator preparation may contain protein phosphatase activity directed towards ACC. The results strongly suggest that under the assay conditions
described for the expression of activation of catalytic activity of ACC, there is little or no apparent dephosphorylation. Indeed, the most purified preparations of ACC activator do not contain any detectable phosphatase activity towards the model substrates histone III-S and casein. The activation of ACC occurs rapidly, in a time dependent manner (within 20 min at 37°C) and involves protein-protein interaction which is antagonized by avidin. The interactions between ACC, avidin and activator protein suggest that the activator not only induces conformational change at the active site of ACC but may also bind in such a way as to be displaced (perhaps directly) by avidin. From the data presented it is concluded that this acetyl-CoA carboxylase activator protein represents a novel factor which may be involved in the short term regulation of ACC activity.Medicine, Faculty of
Biochemistry and Molecular Biology, Department of
Graduate
12
Shriver, Brent James. « Studies on the role of the mitochondrial subunits of acetyl CoA carboxylase and formation of acetyl CoA carboxylase holoenzyme / ». The Ohio State University, 1989. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487683756126816.
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Matas, Nada. « Molecular genetics of human arylamine N-acetyl transferases ». Thesis, University of Oxford, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.338241.
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Yuen, Wai-lan, et 袁慧蘭. « Expression of acetyl-histone H4 in breast cancer ». Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2014. http://hdl.handle.net/10722/206593.
Texte intégralRésumé :
Altered histone modifications are known to be observed in cancer cells. Acetylation of histone H4 (acetyl-H4) occurs reversibly on its amino-terminal end at four lysines positions 5, 8, 12 and 16 by Histone Acetyltransferase (HATs). Acetyl-H4 is responsible for a complex set of post-translational modifications that regulate the accessibility of DNA, transcription activation and DNA repair processes. Acetyl-H4 can also acetylate non-histone proteins which eventually control numerous cell signal pathways such as 53BP1, BRCA, AKT. Accumulated evidence showed that P13K, AKT controls the survival signaling pathway and is crucial in developing in drug resistance. This study investigates the global level of all lysine sites of acetyl-H4, its association with p-AKT as well as its prognostic significance in breast cancer.
The expression levels of acetyl-H4 were assessed by immunohistochemistry on 102 cases of breast cancer from Queen Mary Hospital in Hong Kong using tissue microarray technology. Nuclear expression of acetyl-H4 was scored and SPSS used for statistical analysis. p-AKT expression data previously obtained in our laboratory (Chen et al.) was also retrieved for correlation with nuclear acetyl-H4 scores. Nuclear acetyl-H4 scores were analyzed for association with a) various clinico-pathological parameters, b) luminal subtypes (ER-and PR-positive), HER-2-positive and triple negative breast cancer, c) p-AKT in breast cancer and d) patient survival by Kaplan-Meier analysis and Cox-regression.
By Pearson correlation test, we observed high acetyl-H4 expression was significantly associated with PR-positive breast cancer but not correlated with other clinical parameters and phenotypes of breast cancers (p>0.05). High acetyl-H4 expression was not correlated with p-AKT activity (p=0.84), although it showed inverse correlation with high nuclear p-AKT score. By Kaplan-Meier and Cox-regression analysis, high nuclear acetyl-H4 expression was significantly correlated with poor disease-specific survival in invasive ductal carcinoma (p=0.008 and 0.017 respectively). Multivariate Cox regression analysis confirmed high acetyl-H4 expression (p=0.047) when analyzed together with lymph node involvement (p=0.032) and T-stage (p=0.008) was an independent predictor of poor disease-specific survival in invasive ductal carcinoma.
Our results suggest that high acetyl-H4 expression is significantly associated with PR-positive phenotype and lower disease-free survival. The expression of acetyl-H4 was not correlated with p-AKT. Acetyl-H4 may be a potential biomarker to predict poor disease-specific survival for invasive ductal carcinoma. Further investigation is needed for possible use as therapeutic targeting for breast cancer.published_or_final_version
Pathology
Master
Master of Medical Sciences
15
Martin, Christopher J. « Analogues of acetyl acetonate as nucleophiles & ; ligands ». Thesis, Loughborough University, 1997. https://dspace.lboro.ac.uk/2134/13914.
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This thesis contains the synthesis of a series of novelligands that include the enantiomerically pure 2-oxazoline moiety. The thesis also considers the application of new nucleophiles for the palladium catalysed allylic substitution reaction. The synthesis of enantiomerically enriched analogues of y-amino butyric acid (GABA) is presented. The first series of ligands are designed as analogues of acetyl acetonate (acac). The ligands include the enantiomerically pure 2-oxazoline ring and a carbonyl moiety. The ligands are available in good yield in two steps. The second series of ligands include a ligating sulfur atom. The synthesis of novel oxazoline-sulfide ligands is detailed. The diastereoselective oxidation of these ligands is considered. Diastereomerically pure oxazoline-sulfoxide ligands are prepared in good yield. New nucleophiles are applied to the palladium catalysed allylic substitution reaction. The substitution products are available in good yield and with excellent stereoselectivity. The synthesis of analogues of GABA is considered. The preparation of enantiomerically enriched a-substituted-y-amino butyric acids is presented. The stereocentre is introduced in the first step of the synthesis. The analogues are subsequently isolated in good yield after six steps.
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Mahmoud, Ahmed B. Abdelwahab. « Synthesis and reactivity of 3-acetyl-2-aminothiophenes ». Thesis, Université de Lorraine, 2016. http://www.theses.fr/2016LORR0318/document.
Texte intégralRésumé :
Un intérêt grandissant pour le système thiéno[2,3-b] pyridine est apparu ces trois dernières décennies. De nombreux chercheurs ont présentés des composés basés sur ce système comme traitement possible de l'anxiété et de la dépression, comme bactéricide, contre l'inflammation et la leishmania, la malaria et les maladies auto-immunes. Les ortho-amino acyl thiophènes sont des produits de départ possible pour synthétiser ces motifs. L'accès à ce type de composés sera la première étape de ce travail. Nous décrivons ici la première synthèse de 3-acétyl-2-aminothiophènes en utilisant la réaction à 3 composants de Gewald. Ces composés montrent différents modes de cyclisation dans le cas de traitement avec le réactif de Vilsmeier-Haack. comparé au ortho aminoacétophénones, leurs analogues benzéniques. Ceci semble être du à la présence du noyau thiophénique. Cette réaction a permis l'accès à de nouveaux dérivés 4-chlorothiéno[2,3-b]pyridines. Ces derniers ont été couplés via la réaction de Buchwald-Hartwig catalysée par le palladium.à des anilines avec des rendements moyens à bons. D'autre part, les 4-chloro-3-formylthiéno[2,3-b]pyridines ont été préparés par réaction du réactif de Vilsmeier-Haack sur les acétamido thiophènes correspondants dans les conditions classiques. Ces dérivés ne sont pas accessibles sans la protection de l'amine et non plus à partir des dérivés chlorés en 4. La synthèse de 4-méthylthiéno[2,3-b]pyridines a pu être réalisée par réaction des 3-acétyl-2-aminothiophènes avec des cétones dans les conditions de FriedländerSignificant interest in the thieno[2,3-b]pyridine nucleus has arisen during the last three decades. Many researchers have reported the use of compounds based on this scaffold as a possible treatment of anxiety and depression, bacterial infection, inflammation, leishmaniasis, malaria and autoimmune diseases. Ortho-amino acyl thiophenes are possible starting material allowing to reach the thienopyridine structure. Access to these compounds was our first task for this thesis. We report here the first synthesis of 3-acetyl-2-aminothiophene by using the three-component Gewald reaction. These compounds exhibit a different mode of cyclisation in the reaction with Vilsmeier–Haack reagent than that reported for the reaction with o-aminoacetophenone, which could be ascribed to the influence of the thiophene nucleus. This simple, two-step reaction allows the construction of some novel 4-chlorothieno[2,3-b]pyridine derivatives from very simple building unit while which reacted further with aniline by palladium-catalysed C–N cross-coupling to give the coupled product in moderate to high yield. On other hand, 4-chloro-3-formylthieno[2,3-b]pyridine derivatives were synthesized by reaction between protected 3-acetyl-2-aminothiophenes and vilsmeier-Haack reagent under normal conditions. These products were not accessible neither without N-protection of the starting materials nor by reaction between the reagent and 4-chlorothieno [2,3-b]pyridine under any condition. Some derivatives of 4-methylthieno[2,3-b]pyridine were prepared by reaction between 3-acetyl-2-aminothiophene and some ketones under Friedländer condition
17
Galley, Peter Timothy. « The development of enzyme electrodes for neurophysiology ». Thesis, Imperial College London, 1991. http://hdl.handle.net/10044/1/46777.
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Lee, Weissy Michelle. « Non-covalent control of mammalian acetyl-CoA carboxylase isoforms ». Thesis, University of British Columbia, 2010. http://hdl.handle.net/2429/21518.
Texte intégralRésumé :
Acetyl-CoA carboxylase (ACC) plays several crucial roles in lipid metabolism and has been identified as a potential drug target for the treatment of obesity and cancer. Many aspects of ACC structure, function and control remain unclear and my general goal was to provide new insights into two unresolved areas. The first part of this thesis describes work to characterize the key allosteric site that is responsible for citrate-induced ACC activation. The second area addressed is the hypothesis that protein-protein interactions provide critical aspects of ACC control. The effects of citrate on ACC were probed by studying the effects of pyridoxal phosphate (PLP), modeled on earlier studies of phosphofructokinase. A comprehensive assessment of the inhibition kinetics of ACC by PLP provides support for the effects of PLP being non-competitive with respect to substrates and therefore perhaps mediated by binding to a non-catalytic site. Further studies established methods for covalent attachment of PLP via Schiff base reduction with sodium borohydride and set the stage for more precise localization of PLP binding. To define proteins that interact specifically with ACC, techniques were established to separate large polymeric forms of ACC from smaller dimeric forms of the enzyme by size exclusion chromatography. Analysis of the citrate-induced ACC polymers by tandem mass spectrometry led to the identification of a small number of proteins that consistently associated with ACC in a citrate-dependent manner, including fatty acid synthase (FASN) and tubulin. The interactions of ACC with FASN and tubulin were further explored by Western blotting, co-immunoprecipitation, ACC activity assays and immunofluorescence analysis of primary rat hepatocytes. The evidence from several complementary experimental approaches supports specific interactions between ACC and tubulin. Tubulin appears to have subtle effects on ACC catalytic activity and may be more critical for structural organization and cellular localization of ACC. Immunofluorescence microscopy of ACC within primary rat hepatocytes led to novel insights, notably that ACC is localized into discrete structures rather than being distributed through the cytosolic compartment. This work opens the way to further characterization of the relevant subcellular structures and the role this localization plays in the control of ACC isoforms.
19
Guo, Jian Xin. « Chiroptical properties of Lyotropic (Acetyl)(Ethyl)cellulose liquid crystals ». Thesis, McGill University, 1992. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=39513.
Texte intégralRésumé :
(Acetyl)(ethyl)cellulose (AEC) polymers with an ethyl degree of substitution (DS) of 2.5 and acetyl DS ranging from 0 to 0.5 form chiral nematic liquid crystals in many organic solvents. The chiroptical properties of these lyotropic AEC mesophases are extremely sensitive to the acetyl DS of AEC and the nature of the solvents although the acetyl group and solvents are achiral and all the polymers share the same chiral cellulose backbone. As the acetyl DS increases from 0 to 0.5, the pitch of AEC mesophases in a given solvent varies from a few nanometer to infinity and a reversal of handedness occurs as a compensated degree of acetylation (DA$ sp*$), where the corresponding mesophase is characterized by an infinite pitch and the absence of macroscopic chirality. The value of DA$ sp*$ and the sign of the temperature dependence of pitch depend on the solvent. Achiral dyes dissolved in these AEC mesophases display liquid crystal induced circular dichroism (LCICD), which results from the helicoidal orientation of the dyes by their chiral matrices. The sign and magnitude of the LCICD are correlated with the handedness and pitch of the AEC mesophases. The mechanism for the handedness inversion for lyotropic AEC mesophases with variation in acetyl DS is discussed.
20
Day, Philip John. « The acetyl coenzyme A binding site of chloramphenicol acetyltransferase ». Thesis, University of Leicester, 1990. http://hdl.handle.net/2381/35203.
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Jamonnak, Nuttara. « Novel N(Epsilon)-Acetyl-Lysine Analogs : Synthesis and Application ». University of Akron / OhioLINK, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=akron1216313957.
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Appleton, Martin Lee. « Part 1, NMR assignments of acetyl and trityl groups in derivatized carbohydrates via proton-carbon long-range couplings ; Part 2, the conformational equilibria of 1,2,3,4-tetra-O?-acetyl-?-D-ribopyranose and 1,2,3,4-tetra-O?-acetyl-?-D-xylopyranose / ». The Ohio State University, 1988. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487591658173866.
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Günther, Simone Manuela. « Molekularbiologische Untersuchungen der Acetyl-CoA Carboxylase (EC 6.4.1.2) verschiedener Vertreter der Gramineen = Molecularbiological investigations on the acetyl-CoA-carboxylase (EC 6.4.1.2) of different grasses / ». Karlsruhe : Botan. Inst. d. Univ, 1998. http://www.gbv.de/dms/bs/toc/246324953.pdf.
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Götzl, Sebastian. « Biochemische und strukturelle Untersuchungen an Proteinen des reduktiven Acetyl-CoA-Weges ». Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2014. http://dx.doi.org/10.18452/17072.
Texte intégralRésumé :
Zahlreiche strikt anaerob lebende Mikroorganismen, darunter acetogene Bakterien, Sulfatreduzierer und methanogene Archaeen, nutzen den reduktiven Acetyl-CoA-Weg zur autotrophen Kohlenstoff-Fixierung oder Energiegewinnung. Die letzten Schritte der Acetyl-CoA-Bildung beruhen hierbei auf dem Zusammenspiel dreier Proteine, dem Corrinoid-Eisen/Schwefel-Protein (CoFeSP), der Methyltetrahydrofolat:CoFeSP-Methyltransferase (MeTr) und dem Acetyl-CoA-Synthase/CO-Dehydrogenase-Komplex (ACS/CODH). In der vorliegenden Arbeit wurde die Substratbindung an MeTr durch thermodynamische und kinetische Messungen untersucht. MeTHF bindet stärker an das Enzym als das demethylierte Produkt Tetrahydrofolat (THF) und scheint dabei einem einstufigen Bindungsmodell zu folgen. Das Substrat wird bei der Bindung an MeTr protoniert, wobei Asn200 eine protonierte H-N5(+)-CH3-Position des MeTHF durch eine alternative Konformation stabilisieren könnte. Asp44 und Asp76 bilden eine funktionelle Dyade bei der Substratbindung, kommen als Protondonoren zur Substrataktivierung jedoch nicht in Frage. Die Kristallstruktur von CoFeSP wurde erstmals vollständig mit der flexiblen N-terminalen [4Fe4S]-Cluster-Bindedomäne bestimmt. Die für die Cobalamin-Bindedomäne erwarteten Konformationsänderungen wurden anhand der Interaktion mit dem reduktiven Aktivator von CoFeSP (RACo) analysiert. Durch Förster-Resonanzenergietransfer wurde eine Annäherung der ortsspezifisch markierten CoFeSP-Positionen beobachtet und anhand des Fluoreszenzsignals die Kinetik der Komplexbildung mit RACo bestimmt. Durch gepulste Elektronendoppelresonanz konnte ebenfalls eine Abstandsänderung nachgewiesen werden. ACS wurde als apo-Enzym gereinigt und durch NiCl2-Rekonstitution in die aktive Form überführt. Durch die Kristallisation der C-terminalen ACS-Domäne wurden hochaufgelöste Strukturen erzeugt, welche eine Diskussion der strukturellen Details des aktiven Zentrums ermöglichen.Several anaerobic microorganisms, including acetogenic bacteria, sulfate-reducing bacteria and methanogenic archaea operate the reductive acetyl-CoA pathway for autotrophic carbon fixation or to gain energy. The last steps of acetyl-CoA formation rely on three enzymes, the corrinoid-iron/sulfur-protein (CoFeSP), the methyltetrahydrofolate:CoFeSP methyltransferase (MeTr) and the acetyl-CoA synthase/CO dehydrogenase complex (ACS/CODH). Substrate binding to MeTr was investigated by thermodynamic and kinetic meassurements. MeTHF binds slightly stronger than the demethylated product tetrahydrofolate (THF), likely following a simple one-step-binding mechanism. Substrate binding to MeTr is coupled to proton uptake. A H-N5(+)-CH3-transition state of MeTHF could be stabilized by an alternative conformation of Asn200. Asp44 and Asp76 form a functional dyade in substrate binding but can be excluded as proton donors for substrate activation. The crystal structure of CoFeSP was solved completely, including the previously disordered N-terminal [4Fe4S]-cluster binding domain. The expected conformational change of the corrinoid binding domain was characterized by analyzing the interaction between CoFeSP and its reductive activator (RACo). An approach of the labeled CoFeSP positions in the CoFeSP:RACo complex was observed by Förster resonance energy transfer. Based on the corresponding fluorescence signal, the kinetics of complex formation were meassured in solution. Pulsed electron double resonance also showed that the labeled positions approach upon complex formation. Full-length ACS was purified in the apo state. A reconstitution of the A-cluster with NiCl2 resulted in active enzyme. Different crystal structures of the isolated C-terminal domain of ACS were solved at high resolution. Therefore, structural details of the active site could be discussed.
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Bramlett, Matthew Richard. « Mechanistic investigations of the A-cluster of acetyl-CoA synthase ». Texas A&M University, 2004. http://hdl.handle.net/1969.1/3233.
Texte intégralRésumé :
The A-cluster of acetyl-CoA synthase (ACS) catalyzes the formation of acetyl-
CoA from CO, coenzyme-A, and a methyl group donated by a corrinoid iron-sulfur
protein. Recent crystal structures have exhibited three different metals, Zn, Cu, and Ni,
in the proximal site, which bridges a square-planar nickel site and a [Fe4S4] cubane.
Contradicting reports supported both the nickel and copper containing forms as
representing active enzyme. The results presented here indicate that copper is not
necessary or sufficient for catalysis and that copper addition to ACS is deleterious.
Several proposed mechanisms exist for the synthesis of acetyl-CoA, the two most
prominent are the Âparamagnetic and Âdiamagnetic mechanisms. The ÂdiamagneticÂ
mechanism proposes a two electron activation that precedes methylation to produce an
EPR silent Ni2+-CH3 species. This then reacts with CO and coenzyme-A to form acetyl-
CoA and regenerate the starting species. The Âparamagnetic mechanism assumes a one
electron activation prior to the methylation of the paramagnetic Ni1+-CO state to form an
unstable Ni3+-acetyl species. This is immediately reduced by an electron shuttle.
Results are presented here that no shuttle or external redox mediator is necessary for
catalysis. This supports the Âdiamagnetic mechanism, specifically that a two-electron
reductive activation is necessary and that the Ni1+-CO species is not an intermediate.
The two-electron reductive activation required by the Âdiamagnetic mechanism
results in an unknown electronic state. Two proposals have been made to describe this
form of the A-cluster. The first hypothesis from Brunold et al involves a one-electron
reduction of the [Fe4S4]2+ cube and a one-electron reduction of the Nip
2+. This should
result in a spin-coupled state that is S = integer. The Ni0 hypothesis requires both
electrons to localize on the Nip
2+ forming a zero-valent proximal nickel. Mössbauer
spectroscopy has been used to probe the oxidation state and spin state of the [Fe4S4] cube
in the reduced active form. No integer spin system is found and this is interpreted as
supporting the Ni0 hypothesis. Additionally, spectra are presented that indicate the
heterogeneous nature of the A-cluster is not caused by the occupancy of the proximal
site.
26
Scoponi, Giulia. « Lewis acid catalysed direct glycosylation of N-acetyl-D-glucosamine ». Master's thesis, Alma Mater Studiorum - Università di Bologna, 2017. http://amslaurea.unibo.it/14450/.
Texte intégralRésumé :
Incorporation of the relevant monosaccharide N-Acetyl-D-glucosamine (GlcNAc) into synthetic oligosaccharides by chemical glycosylation is still a very challenging object of studies, since direct reactions are low yielding. This issue is generally ascribed to its low solubility in common solvents and to the formation of a poorly reactive oxazoline intermediate, which is typically bypassed by introducing extra synthetic steps to avoid the presence of the NHAc moiety during glycosylation. Recently, a new direct Lewis acids-catalysed GlcNAc-ylation protocol has been disclosed, with acylated donors appearing to hold potential for high yielding glycosylation reactions. This master project focused indeed on a novel synthesis of promising 1-acyl GlcNAc donors, in order to test them in direct Lewis acid catalysed glycosylation without the need of N-protecting groups. Screening of various Lewis acids and reaction conditions with these acylated donors has been carried out, in presence of reactive primary alcohols as well as more challenging carbohydrate acceptor alcohols. These experiments demonstrated that the fine tuning of the leaving group combined with a suitable metal triflate could lead to a successful reaction outcome in the direct glycosylation.
Successful methodology of this kind would provide rapid access to naturally occurring N-glycan motifs, such as the highly relevant human milk oligosaccharides (HMOs).
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Colston, Nicola Jane. « Palladium-catalysed enantioselective hydrogenation of N-acetyl dehydrophenylalanine methyl ester ». Thesis, Cardiff University, 2004. http://orca.cf.ac.uk/55407/.
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Baxter, Scott. « Directed evolution of an industrial N-acetyl-amino acid racemase ». Thesis, University of Edinburgh, 2013. http://hdl.handle.net/1842/7686.
Texte intégralRésumé :
The use of stereoselective aminohydrolases (acylases) in kinetic resolutions is a commonly employed industrial route to both L- and D- α-amino acids from Nacetylated- DL-starting materials. However, a flaw in this process is the need for repeated racemisation steps of the non-desired enantiomer to achieve yields >50%. A solution to this drawback would be a dynamic kinetic resolution driven by an in situ racemisation step that would allow the yield to approach 100% A cheap and “green” catalyst for this racemisation would be an enzyme such as N-acyl amino acid racemase (NAAAR) from the actinobacteria Amycolatopsis sp. Ts-1-60. This enzyme requires no organic cofactor, is stable at high temperatures (~60°C) and importantly, shows no racemase activity toward free amino acids. Unfortunately, the activity of NAAAR with N-acetyl substrates is low and reported to suffer from inhibition above substrate concentrations of 50 mM, prohibiting its use in NAAAR/acylase coupled dynamic kinetic resolutions under industrial conditions. In an attempt to remove these limitations, directed evolution has been applied to the Amycolatopsis Ts-1-60 NAAAR to engineer a variant enzyme with increased activity towards N-acetyl substrates. An improved variant NAAAR may allow for a commercial NAAAR/acylase coupled dynamic resolution process. Directed evolution has proven to be a highly versatile and successful tool for protein engineering. However, the ability to screen for improved variants is often technically difficult or time consuming and in the case of NAAAR this is especially true as the substrate and product are simply enantiomers of an N-acetyl amino acid. To overcome this, an enantioselective genetic selection system has been employed to allow the screening of mutagenic NAAAR libraries. After several rounds of selection, a NAAAR variant (NAAAR G291D F323Y) has been isolated with increased racemase activity towards a range of synthetically useful N-acetyl substrates. This enzyme has been over-expressed, purified and its characteristics compared to the wild-type and other variants discovered during the evolution process. NAAAR G291D F323Y has been crystallised to 2.71 Å allowing a molecular basis for the increase in catalytic activity to be proposed. Coupling of this enzyme with a stereoselective acylase has been used to produce enantiopure amino acids in >99% yield, twice the inherent 50% maximum yield of acylase based resolutions. Early results suggest this NAAAR variant has the potential to be employed on a multi kilogram scale for the economical production of enantiopure L- and D- α-amino acids.
29
Seago, Amanda Jane Helen. « Studies towards the synthesis of pseudo-N-acetyl neuraminic acid ». Thesis, University of Liverpool, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.365900.
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McGlone, Adam Phillip. « Enantioselective recognition of carboxylates : N-acetyl amino acids and Naproxen ». Thesis, University of Bristol, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.419688.
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Schmidt, Joel D. « Functional analysis of paralogous genes in acetyl coenzyme A metabolism ». [Ames, Iowa : Iowa State University], 2008. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3307102.
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Jäger, Karin. « Glycosyl-phosphatidylinositol-anchored acetyl-cholinesterase and phosphatidylinositol-specific phospholipase C / ». Bern, 1990. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
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Bowers, Diana Fullen. « Identification and characterization of acetyl CoA carboxylase as a glycoprotein / ». The Ohio State University, 1991. http://rave.ohiolink.edu/etdc/view?acc_num=osu148768711592399.
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Lima, ?dila Lorena Morais. « Purifica??o e caracteriza??o parcial de duas N-acetil-?-hexosaminidases do Equinoderma marinho Echinometra lucunter ». Universidade Federal do Rio Grande do Norte, 2006. http://repositorio.ufrn.br:8080/jspui/handle/123456789/12620.
Texte intégralRésumé :
Made available in DSpace on 2014-12-17T14:03:43Z (GMT). No. of bitstreams: 1
AdilaLML.pdf: 743306 bytes, checksum: 8c2b4b2827dafcc2f2edd7664a266e10 (MD5)
Previous issue date: 2006-11-30Two b-N-acetylhexosaminidases (F11 e F15) were purified from Echinometra lucunter gonads extracts. The purified enzymes were obtained using ammonium sulfate fractionation, followed by gel filtration chromatographies (Sephacryl S-200, Sephadex G-75 and Sephacryl S-200). The F11 fraction was purified 192.47 -fold with a 28.5% yield, and F15 fraction 85.41 -fold with a 32.3% yield. The molecular weights of the fractions were 116 kDa for F11 and 42 kDa for F15 using SDS-PAGE. In Sephacryl S-200, F15 was 84 kDa, indicating that it is a dimeric protein. When p-nitrophenyl-?-D-glycosaminide was used as substrate, we determined an apparent Km of 0.257 mM and Vmax of 0.704 for F11 and for F15 the Km was 0.235 mM and Vmax of 0.9 mM of product liberated by hour. Both enzymes have optimum pH and temperature respectively at 5.0 and 45 ?C. The enzymes showed inhibition by silver nitrate, while the glucuronic acid was a potent activator. The high inhibition of F15 by N-etylmaleimide indicates that sulphydril groups are involved in the catalysis of synthetic substrate
Neste trabalho foram purificadas e caracterizadas parcialmente duas N-acetil-b- hexosaminidases (F11 e F15) extra?das de g?nadas do equinoderma marinho Echinometra lucunter. As enzimas foram purificadas com protocolo seq?encial por precipita??o com sulfato de am?nio e cromatografias de exclus?o molecular (Sephacryl S-200, Sephadex G-75 e Sephacryl S-200). A fra??o F11 foi purificada 192,47 vezes com recupera??o de 28,5% e F15 85,41 vezes com recupera??o de 32,3%. Suas massas moleculares, determinadas por eletroforese em gel de poliacrilamida com SDS, foram respectivamente 116 e 42 kDa. Em Sephacryl S-200 F15 apresentou massa molecular de 84 KDa, sugerindo que esta enzima possui forma dim?rica. Utilizando-se p-nitrofenil N-acetil-b-glicosamin?deo como substrato obtivemos Km aparente de 0,257 mM e Vmax de 0,704 unidades de absorb?ncia a 405 nm / h para a fra??o 11, e 0,235 mM e Vmax de 0,9 unidades de absorb?ncia a 405 nm / h para F15. Ambas fra??es apresentaram pH e a temperatura ?tima de cat?lise 5,0 e 45 ?C, respectivamente. A atividade N-acetil-b-glicosaminid?sica foi potencialmente inibida por prata, iodoacetamida, N-etilmaleimida e PMSF. A forte inibi??o de F15 por N-etilmaleimida indica o envolvimento de radicais sulfidrila na hidr?lise do substrato sint?tico, caracterizando tamb?m ser uma enzima altamente sensitiva a este sal
35
Musfeldt, Meike. « ADP-bildende Acetyl-CoA-Synthetasen aus hyperthermophilen Archaea molekularbiologische und biochemische Charakterisierung von neuartigen Enzymen der Acetat-Bildung und ATP-Synthese / ». [S.l. : s.n.], 2001. http://e-diss.uni-kiel.de/diss/d482.pdf.
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Hartness, Marion Elizabeth. « Design and synthesis of novel inhibitors of Tip60 histone acetyl-transferase ». Thesis, University of Newcastle Upon Tyne, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.430340.
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Heesom, Kate J. « The regulation of acetyl-CoA carboxylase by insulin in adipose tissue ». Thesis, University of Bristol, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294552.
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Shu, Ningcheng. « Structural studies of biotinyl domain of E. coli acetyl-CoA carboxylase ». Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620559.
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KUO, MING-WEN. « ROLE OF N-ACETYL CYSTEINE IN PREVENTING AGE-RELATED HEARING LOSS ». University of Cincinnati / OhioLINK, 2007. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1172356377.
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Kornacki, Catherine. « MANIPULATING OIL SEED BIOCHEMISTRY TO ENHANCE THE PRODUCTION OF ACETYL-TAGS ». Thesis, Kansas State University, 2016. http://hdl.handle.net/2097/35753.
Texte intégralRésumé :
Master of ScienceBiochemistry and Molecular Biophysics Interdepartmental Program
Timothy P. Durrett
Using vegetable oils directly as an alternative biofuel presents several problems as such oils typically possess poor fuel qualities including high viscosity, low volatility, and poor cold temperature properties. The ornamental shrub Euonymus alatus produces unusual acetyl-1,2-diacyl-sn-glycerols (acetyl-TAGs) that have an acetyl group in the sn-3 position instead of a long chain fatty acid. The presence of this sn-3 acetyl-group give acetyl-TAGs properties desirable for biofuels, such as reduced viscosity, comparted to the normal long chain triacyglycerols found in most vegetable oils. Acetyl-TAGs are synthesized by the Euonymus alatus diacylglycerol acetyltransferase (EaDAcT) and Euonymus fortunei diacylglycerol acetyltransferase (EfDAcT) enzymes. Both enzymes catalyze the transfer of an acetyl group from acetyl-CoA to diaclglycerol (DAG) to produce acetyl-TAGs. Previous work demonstrated that expression of EaDAcT combined with the suppression of a diacylglycerol aceyltransferase (DGAT1) in Camelina sativa led to seeds with 85 mol % acetyl-TAGs. Increasing acetyl-TAG levels further was explored using two strategies. Over expression of citrate lyase to increase the pool of acetyl-CoA to be used as a substrate for the acetyltransferase enzymes failed to increased levels of acetyl-TAGs. A second approach involved expressing EfDAcT in Camelina sativa. EfDAcT has demonstrated higher activity in vitro and in vivo and its expression in yeast leads to approximately 50 % higher levels of acetyl-TAGs compared to EaDAcT. The expression of EfDAcT coupled with the suppression of DGAT1 in Camelina sativa resulted in 90 mol % acetyl-TAGs in the transgenic seeds. Levels of EfDAcT protein analyzed in developing transgenic Camelina sativa seeds across a 40 day time period were highest at 15 and 20 days after flowering. Following these time points acetyl-TAG accumulation increased rapidly, coinciding with the higher enzyme expression levels. The optimization of additional promoters to ensure expression of EfDAcT in the last half of seed development could represent another way to further increase acetyl-TAGs in the future.
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Karalija, Amar. « Diagnostic and therapeutic strategies following spinal cord and brachial plexus injuries ». Doctoral thesis, Umeå universitet, Anatomi, 2016. http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-127519.
Texte intégralRésumé :
Traumatic injuries to the spinal cord and brachial plexus induce a significant inflammatory response in the nervous tissue with progressive degeneration of neurons and glial cells, and cause considerable physical and mental suffering in affected patients. This thesis investigates the effects of the antioxidants N-acetyl-cysteine (NAC) and acetyl-L- carnitine (ALC) on the survival of motoneurons in the brainstem and spinal cord, the expression of pro-apoptotic and pro-inflammatory cell markers, axonal sprouting and glial cell reactions after spinal hemisection in adult rats. In addition, a novel MRI protocol has been developed to analyse the extent of neuronal degeneration in the spinal cord. Rubrospinal neurons and tibial motoneurons were pre-labelled with the fluorescent tracer Fast Blue one week before cervical C3 or lumbar L5 spinal cord hemisection. The intrathecal treatment with the antioxidants NAC (2.4mg/day) or ALC (0.9 mg/day) was initiated immediately after injury using Alzet2002 osmotic mini pumps. Spinal cord injury increased the expression of apoptotic cell markers BAX and caspase 3, induced significant degeneration of rubrospinal neurons and spinal motoneurons with associated decrease in immunoreactivity for microtubule-associated protein-2 (MAP2) in dendritic branches, synaptophysin in presynaptic boutons and neurofilaments in nerve fibers. Immunostaining for the astroglial marker glial fibrillary acidic protein and microglial markers OX42 and ED1 was markedly increased. Treatment with NAC and ALC attenuated levels of BAX, caspase 3, OX42 and ED1 expression after 2 weeks postoperatively. After 4-8 weeks of continuous intratheca ltreatment, NAC and ALC rescued approximately half of the rubrospinal neurons and spinal motoneurons destined to die, promoted axonal sprouting, restored the density of MAP2 and synaptophysin immunoreactivity and reduced the microglial reaction. However, antioxidant therapy did not affect the reactive astrocytes in the trauma zone. The inflammation modulating properties of ALC were also studied using cultures of human microglial cells. ALC increased the microglial production of interleukin IL-6 and BDNF, thereby possibly mediating the anti-inflammatory and pro-regenerative effects shown in vivo. To study degeneration in the spinal cord following pre-ganglionic and post-ganglionic brachial plexus injuries, adult rat models of ventral root avulsion and peripheral nerve injury were used. A novel MRI protocol was employed and the images were compared to morphological changes found in histological preparations. Ventral root avulsion caused degeneration of dendritic branches and axonal terminals in the spinal cord, followed by significant shrinkage of the ventral horn. Extensive astroglial and microglial reactions were detected in the histological preparations. Peripheral nerve injury reduced the density of dendritic branches but did not cause shrinkage of the ventral horn. Quantitative analysis of MRI images demonstrated changes in the ventral horn following ventral root avulsion only, thus validating the developed MRI technique as a possible tool for the differentiation of pre-ganglionic and post-ganglionic nerve injuries.
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Keogh, Michael-Christopher. « Regulation and function of CD2 in the mouse ». Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.321779.
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Jin, Huanan. « Genetic, biochemical and physiological studies of acetyl-CoA metabolism via acyl-condensation ». [Ames, Iowa : Iowa State University], 2010. http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqdiss&rft_dat=xri:pqdiss:3403808.
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Danowski, Lisa Marie. « CHARACTERIZATION OF CONIFERYL ALCOHOL ACETYL TRANSFERASE (CAAT) FROM SWEET BASIL (OCIUM BASILICUM) ». Thesis, The University of Arizona, 2009. http://hdl.handle.net/10150/192317.
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Tessier, Wayne Danny. « The role of aldehyde dehydrogenases in Acetyl-CoA production by Saccharomyces cerevisiae ». Thesis, University of Hull, 1998. http://hydra.hull.ac.uk/resources/hull:11284.
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Schmidt, Claudia [Verfasser]. « Acetyl-Lupeolsäure - ein potentieller natürlicher Wirkstoff zur Behandlung chemoresistenter Tumore / Claudia Schmidt ». Ulm : Universitätsklinikum Ulm, 2013. http://d-nb.info/1031237739/34.
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Morrice, Jane. « Isolation and characterisation of the acetyl-CoA carboxylase gene of Aspergillus nidulans ». Thesis, University of East Anglia, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.267542.
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Sellwood, Chloe. « Effects of manipulating expression of acetyl-coa carboxylase in Brassica napus embryos ». Thesis, University of East Anglia, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.251652.
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Chaure, Pushpalata Trimbak. « A regulatory role for acetyl-CoA synthetase (acu-5) in Neurospora crassa ». Thesis, University of Reading, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.239059.
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Choudhury, Mahua Shukla Shivendra D. « Alcohol induced histone acetylation mediated by histone acetyl transferase GCN5 in liver ». Diss., Columbia, Mo. : University of Missouri-Columbia, 2008. http://hdl.handle.net/10355/6866.
Texte intégralRésumé :
The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Title from PDF of title page (University of Missouri--Columbia, viewed on April 6, 2010). Vita. Thesis advisor: Shivendra D. Shukla. "August 2008" Includes bibliographical references