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Boehm, Haydn M. "Tandem radical cascade cyclisation reactions in steroid synthesis." Thesis, University of Nottingham, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.364673.
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Neunzig, Jens [Verfasser], and Rita [Akademischer Betreuer] Bernhardt. "The role of sulfonated steroids and parmaceutical compouds in steroid hormone biosynthesis / Jens Neunzig. Betreuer: Rita Bernhardt." Saarbrücken : Saarländische Universitäts- und Landesbibliothek, 2014. http://d-nb.info/1064305865/34.
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Depledge, Nigel William. "Design of inhibitors for two oxygen-requiring metalloenzymes in steroid biosynthesis." Thesis, University of Southampton, 1997. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.242299.
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Lucki, Natasha Chrystman. "Characterization of the role of acid ceramidase in adrenocortical steroid hormone biosynthesis." Diss., Georgia Institute of Technology, 2011. http://hdl.handle.net/1853/42804.
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Sphingolipids modulate multiple cellular functions, including steroid hormone biosynthesis. Sphingosine is an antagonist ligand for the nuclear receptor steroidogenic factor 1 (SF-1), which is the primary transcriptional regulator of most steroidogenic genes. Furthermore, sphingosine-dependent repression of SF-1 function is dependent on the expression of acid ceramidase (ASAH1), an enzyme that forms sphingosine. Based on these data, I hypothesized that ACTH/cAMP signaling regulates ASAH1 function at both transcriptional and post-transcriptional levels. In addition, because SF-1 is predominantly a nuclear protein, I postulated that ASAH1 modulates SF-1 function and, therefore, steroidogenic gene expression by controlling the nuclear concentrations of SPH. To test these hypotheses, I first examined the effect of chronic ACTH/cAMP signaling on the transcription of the ASAH1 gene. Next, the functional significance of ASAH1 expression in adrenocortical cells was probed by generating an ASAH1-knockdown cell line. I subsequently characterized the role of ASAH1 as a transcriptional nuclear receptor coregulator. Finally, I defined the role of sphingosine-1-phosphate, a bi-product of ASAH1 activity, in the acute phase of cortisol biosynthesis. Using a variety of experimental approaches, I identified cAMP response element binding protein as an essential transcriptional activator of the ASAH1 gene. Analysis of adrenocortical cells lacking ASAH1 revealed that ASAH1 is a global regulator of steroidogenic capacity. Furthermore, I identified ASAH1 as a nuclear protein and defined the molecular determinants of the interaction between ASAH1 and SF-1. Collectively, this body of work establishes the integral role of ASAH1 in the regulation of ACTH-dependent adrenocortical cortisol biosynthesis.
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Boerboom, Derek. "Gene regulation of prostaglandin and steroid hormone biosynthesis in equine preovulatory follicles." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2000. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape2/PQDD_0021/NQ55454.pdf.
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Rone, Malena Beth. "Role of protein-protein interactions in protein import, cholesterol transport and steroid biosynthesis." Connect to Electronic Thesis (CONTENTdm), 2010. http://worldcat.org/oclc/642829125/viewonline.
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Heerdegen, Desirée [Verfasser], and Franz [Akademischer Betreuer] Bracher. "Synthesis of steroid-like analogues of cholesterol biosynthesis inhibitors / Desirée Heerdegen ; Betreuer: Franz Bracher." München : Universitätsbibliothek der Ludwig-Maximilians-Universität, 2020. http://d-nb.info/1219852112/34.
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Liu, Hong. "Molecular isolation and characterization of Macaca fascicularis hydroxysteroid dehydrogenases involved in sex steroid biosynthesis and metabolism." Thesis, Université Laval, 2007. http://www.theses.ulaval.ca/2007/24499/24499.pdf.
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Reitemeier, Susanne. "Morphologische und immunzytochemische Charakterisierung der Gonaden männlicher Papageienvögel." Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-133392.
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Gefährdete Spezies in Menschenobhut zu reproduzieren und zu erhalten soll dem weltweiten Rückgang zahlreicher Papageienarten entgegenwirken. Der Erfolg solcher Zuchtprogramme wird unter anderem durch begrenzte Kenntnisse über physiologische und pathologische Vorgänge im Fortpflanzungssystem dieser Vogelordnung erschwert.
Ziel der vorliegenden Arbeit war die Etablierung aussagekräftiger Parameter zur Einordnung des Reproduktionsstatus von männlichen Papageienvögeln. Dabei wurde ein Probenumfang fixierter, männlicher Reproduktionsorgane acht verschiedener Gattungen mit standardisierten histologischen und immunzytochemischen Methoden untersucht. Im Vordergrund stand die morphologische Beurteilung der untersuchten Gonaden im Bezug auf Fortpflanzungsaktivität und -status. Gleichzeitig sollten die immunzytochemischen Analysen Aufschluss über die beteiligten Hormone und Enzyme geben. Für die Etablierung vogel-spezifischer Marker wurde als Vertreter der Psittaciformes der Wellensittich (Melopsittacus undulatus, n=45) als Modellspezies ausgewählt. 15 verschiedene Antikörper aus der Gruppe der Steroidrezeptoren, steroidogenen Enzyme, Relaxinpeptide und Proliferationsmarker wurden an dieser Art getestet. Anschließend erfolgte der Transfer der erarbeiteten Methodik auf sieben weitere Papageiengattungen (Nymphicus, Eolophus, Cacatua, Psittacus, Amazona, Ara, Cyanopsitta).
Anhand der Histologie konnten alle untersuchten Gonaden den drei verschiedenen Reproduktionsstadien aktiv, intermediär und inaktiv zugeordnet werden. Hierbei wurden Kriterien wie die Ausdehnung von Samenkanälchen und Interstitium, Morphologie des Keimepithels, Vorhandensein von Lipofuszin in den Samenkanälchen sowie die Teilungsaktivität von Keimzellen herangezogen. Aktive Hoden zeigen ausgedehnte Tubuli und ein schmales Interstitium, ein Keimepithel mit allen Keimzellstadien, wenig Lipofuszin und eine hohe Teilungsaktivität bei den Keimzellen. Inaktive Hoden hingegen besitzen schmale Tubuli und ein breites Interstitium, ein Keimepithel bestehend aus Sertoli-Zellen und Spermatogonien, Massen an Lipofuszin im Lumen der Samenkanälchen und eine geringe Proliferationsrate der Keimzellen.
14 der 15 getesteten Marker konnten mittels Immunzytochemie erfolgreich am Wellensittich etabliert werden. Hinsichtlich der Einordnung des Reproduktionsstatus war in erster Linie ein Absinken der steroidogenen Enzymaktivität von 3β-Hydroxysteroid-Dehydrogenase (HSD) und 17β-HSD-2 bei sexuell inaktiven gegenüber aktiven und intermediären Tieren zu verzeichnen. Auch der Androgenrezeptor (AR) wurde im Ruhestadium nicht mehr exprimiert. Die übrigen Steroidrezeptoren, steroidogenen Enzyme und Relaxinpeptide zeigten variable zelluläre Verteilungsmuster, die keine klare Aussage zum Fortpflanzungsstatus zuließen. Dennoch konnten anhand der Lokalisation dieser Faktoren in Keimzellen, somatischen Zellen des Hodens und Zellen des Nebenhodenepithels funktionelle Gesichtspunkte geklärt werden. Beispielsweise zeigte die Koexistenz des Östrogenrezeptors ERα und des steroidogenen Enzyms Aromatase in Hoden und Nebenhoden, dass nicht nur androgene Einflüsse in die Steuerung der Gonaden involviert sind. Auch der erstmalige Nachweis von Relaxin, Relaxin-like factor und ihren Rezeptoren in testikulären und epididymalen Zellen deutet darauf hin, dass diese die Funktion der beim Vogel nicht vorhandenen Prostata übernehmen.
Zudem ist der Transfer der etablierten immunzytochemischen Methoden auf sieben weitere Papageiengattungen (Nymphicus, Eolophus, Cacatua, Psittacus, Amazona, Ara, Cyanopsitta) gelungen. Auch hier konnten 14 Marker in verschiedenen Zellen von Hoden und Nebenhoden sichtbar gemacht werden. Die teilweise heterogene Verteilung der Marker in verschiedenen Zelltypen war eindeutig spezies-abhängig. Dies hat gezeigt, dass die beim Wellensittich mittels Immunzytochemie erzielten Resultate nur eingeschränkt auf andere Papageienspezies übertragbar sind. Entscheidend für die Beurteilung des Reproduktionsstatus ist daher die individuelle Auswahl der Marker in Abhängigkeit von der untersuchten Spezies.
Die Resultate dieser Studie liefern die Grundlage für weitere Forschungsansätze in der Reproduktionsdiagnostik von Papageienvögeln. Zum einen können die etablierten Marker in Analyse-Systemen zum Einsatz kommen, die nicht-invasiv gewonnene Medien (z. B. Faezes) untersuchen und vor allem in Zuchterhaltungsprogrammen bedrohter Arten hilfreich sind. Zum anderen ist die immunzytochemische Untersuchung von Hodenbioptaten pathologisch veränderter Hoden (z. B. Tumoren oder Entzündungen) als eine sinnvolle Ergänzung der Diagnostik von Infertilität bei männlichen Psittaziden anzusehen.
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Taton, Maryse. "Mecanisme et inhibition rationnelle d'enzymes de la biosynthese des phytosterols." Université Louis Pasteur (Strasbourg) (1971-2008), 1986. http://www.theses.fr/1986STR13224.
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Zschockelt, Lina. "The contribution of steroids and prostaglandins to the lifespan of corpora lutea in domestic cats and lynxes." Doctoral thesis, Humboldt-Universität zu Berlin, Lebenswissenschaftliche Fakultät, 2016. http://dx.doi.org/10.18452/17496.
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Iberische und Eurasische Luchse zeigen einen saisonalen Monoöstrus. Nach der Ovulation findet man frisch gebildete (freshCL) und physiologisch persistierende Gelbkörper (corpora lutea, perCL). Funktionelle perCL verhindern eine Ovulation außerhalb der Zuchtsaison durch konstant erhöhte Progesteron-(P4)-Plasmawerte. Hauskatzen zeigen einen saisonalen Polyöstrus. Nach der Ovulation werden CL gebildet, deren Lebensspanne in Abhängigkeit von einer Trächtigkeit durch unterschiedliche P4-Plasmaprofile charakterisiert ist. Ziel der Dissertation war es, die Synthese und Rezeption von Steroiden und Prostaglandinen (PG) in CL von Feliden zu untersuchen, um potentiell luteotrophe und luteolytische Faktoren zu identifizieren. Während der Gelbkörperphase trächtiger und nicht-trächtiger Katzen weisen CL gleicher Histomorphologie, unabhängig vom Vorhandensein einer Trächtigkeit, ähnliche steroidogene Kapazitäten auf. Die Abnahme der CL-Funktion spiegelt sich im graduellen Verlust der Steroidbiogenese wider. Bei Luchsen ist die steroidogene Kapazität der perCL im Proöstrus herabgesetzt, aber im Metöstrus wieder verstärkt. Die steroidogene Kapazität ist demnach mit verschiedenen CL-Stadien und dem Reproduktionszyklus assoziiert. Die Synthese und Rezeption von PGE2 erfolgen bei Katze und Luchs unabhängig vom CL-Stadium und dem Reproduktionszyklus. Hohe Werte an luteotrophem PGE2 in perCL könnten für die funktionelle und strukturelle CL-Persistenz beim Luchs verantwortlich sein. Der feline CL ist zur Bindung von luteolytischem PGF2alpha fähig, jedoch ist die Kapazität zur Synthese begrenzt. Feliden weisen keine PGF2alpha-assoziierte luteale Regression in Abwesenheit einer Trächtigkeit auf. Allerdings wurden Höchstwerte an PGF2alpha in der Plazenta, wie auch im Plasma (PGFM), im letzten Trächtigkeitstrimester der Katze gemessen. Folglich ist die feline Plazenta zur Synthese von luteolytischem PGF2alpha fähig, welches die CL-Regression und Geburt am Ende der Trächtigkeit ermöglicht.Iberian and Eurasian lynxes exhibit a seasonal monooestrus. After ovulation, freshly formed (freshCL) coexist with physiologically persistent luteal bodies (corpora lutea, perCL). Functional perCL prevent ovulation outside the breeding season through constantly elevated plasma progesterone (P4) levels. Domestic cats show a seasonal polyoestrus. After ovulation, CL are built with lifespans being characterised by different plasma P4 profiles dependent on pregnancy. The aim of the dissertation was to characterise the synthesis and reception of steroids and prostaglandins (PGs) in CL of felids to identify potential luteotrophic and luteolytic factors. During the luteal lifespan of pregnant and non-pregnant cats, CL of equal histomorphology exhibit similar steroidogenic capacities, irrespectively of an ongoing pregnancy. The functional demise of CL mirrors the gradual loss of steroid biogenesis. In lynxes, the steroidogenic capacity of perCL is limited at prooestrus, but is enhanced again during metoestrus. The steroidogenic capacity is thus associated with different CL stages and the reproductive cycle. The synthesis and reception of PGE2 in cat and lynx is independent on the CL stage and reproductive cycle. High levels of luteotrophic PGE2 in perCL might be responsible for the functional and structural CL persistence in lynxes. The feline CL is capable of binding luteolytic PGF2alpha; however, the capacity to synthesise PGF2alpha is limited. Felids show no PGF2alpha-associated luteal regression in the absence of pregnancy. Interestingly, peak levels of PGF2alpha in the placenta, as well as in plasma (PGFM), were measured during the last trimester of pregnancy in the cat. Therefore, the feline placenta is capable of synthesising luteolytic PGF2alpha, which enables CL regression and parturition at the end of pregnancy.
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Gill, H. K. "The biosynthesis of novel plant steroids." Thesis, University of Nottingham, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.371123.
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Hares, Owen. "Synthetic methodology towards inhibitors of aromatase." Thesis, University of Nottingham, 1990. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.278530.
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Babin, Patrick. "Lipoproteines et apolipoproteines plasmatiques chez les poissons teleosteens." Paris 6, 1987. http://www.theses.fr/1987PA066032.
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Caracterisation des lipoproteines plasmatiques et de leurs apolipoproteines chez salmo gairdneri. Determination de leur masse moleculaire et de leur densite. L'etude au long du cycle annuel de reproduction a permis de demontrer la presence de proteines vitellines ovulaires dans le plasma. De plus, le role des lipoproteines, plasmatiques dans la steroidogenese ovarienne a ete etudie
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Boulez, Florence. "Étiologies moléculaires des insuffisances surrénales primaires congénitales : développements statistiques pour la validation du séquençage parallèle massif." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSE1057.
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L'insuffisance surrénale primaire (ISP) se caractérise par un déficit en hormones stéroïdiennes lié à un trouble du cortex surrénal qui expose au risque d'insuffisance aiguë et de menace vitale. Actuellement, 80% des formes pédiatriques d'ISP sont d'origine génétique et 5% restent sans étiologie génétique identifiée. Les récentes découvertes de mutations de gènes du stress oxydant ouvrent le champ des recherches d'anomalies génétiques non spécifiques de la glande surrénale. Le séquençage parallèle massif (MPS) autorise aujourd'hui la réalisation de millions de séquences et l'étude simultanée de plusieurs gènes de plusieurs patients ce qui permet d'accélérer le diagnostic. C'est aussi la technique de choix pour la recherche de nouveaux gènes. Cependant, parmi les défis de cette nouvelle technologie, il est possible de citer la gestion de la très grande quantité de données qu'elle génère et le besoin d'une validation rigoureuse préalable à son utilisation à des fins diagnostiques.Le premier objectif du présent travail était d'établir un diagnostic génétique dans une cohorte de patients atteints d'ISP et de rechercher de nouveaux gènes. L'étude des génotypes et des phénotypes permet de comprendre les mécanismes physiopathologiques pour les engager dans le traitement et le conseil génétique.Le second objectif était le développement de méthodes bio-informatiques et d'inférence statistique pour faciliter le transfert du séquençage classique (Sanger) vers la technique MPS. Ce développement comprend l'analyse graphique de la qualité du séquençage, l'ajustement de modèles log-linéaires pour comparer les propriétés de différents « pipelines », et l'ajustement de modèles additifs généralisés pour estimer les contributions des sources d'erreurs de séquençage. Les analyses statistiques ont considéré chaque paire de bases comme unité statistique et chaque patient comme étude indépendante, ce qui confère à l'analyse simultanée de tous les patients le caractère d'une méta-analysePrimary adrenal insufficiency (PAI) is characterized by an impaired production of steroid hormones due to an adrenal cortex defect. This condition exposes to the risk of acute insufficiency which may be life-threatening. Today, 80% of pediatric forms of PAI have a genetic origin but 5% have no clear genetic support. Recently discovered mutations in genes relative to the oxidative stress have opened the way to research works on genes unrelated to the adrenal gland. Massive Parallel Sequencing (MPS) is now able to perform millions of sequences and study simultaneously several genes in several patients, which accelerates the diagnosis. Above all, MPS is the preferred technique for new gene discoveries. However, among the challenges of this new technology one may cite the management of the huge amount of data MPS generates and the need for a strict validation process before the use of MPS for diagnosis purposes.The first objective of the present work was to establish a genetic diagnosis in a cohort of patients with PAI and search for new genes. Study the genotypes and phenotypes allows a better understanding of the physiopathological mechanisms of PAI and offering appropriate care for the patients and counseling for families. The second objective was the development of bioinformatic and statistical inference methods to help shifting from the classical Sanger sequencing to MPS. This shift involves a graphical analysis of the quality of sequencing, an adjustment of log-linear models to allow comparing the properties of different pipelines, an adjustment of the generalized additive models to allow estimating the contributions of various sources of sequencing errors. The statistical methods have considered each DNA base-pair as a statistical unit and each patient as a separate study which confers the simultaneous study of all patients the status of a meta-analysis
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Smith, Susan Janette. "In vitro biosynthesis of steroids in equine testicular tissue." Thesis, University of Liverpool, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.328222.
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Yates, Phillip John. "Sterol biosynthesis and plant culture growth." Thesis, University of Liverpool, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317319.
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Parker, Stephen R. "Sterol biosynthesis in Aspergillus and its inhibition by azole antimycotics." Thesis, University of Cambridge, 1991. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.307142.
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Al-Shakarchi, E. M. D. "Transformation of sterols in plant tissue cultures." Thesis, Bucks New University, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.384187.
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Pullen, Margaret Leighton. "Studies on sterol biosynthesis mutants of Arabidopsis." Thesis, Durham University, 2005. http://etheses.dur.ac.uk/2952/.
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This thesis examines the gene promoter activity and morphological characteristics of mutants of HYDRA 1 (HYD 1) and HYDRA2 I FACKEL (HYD2 I FK) (Mayer et al. 1991, Topping et al. 1997) from Arabidopsis. These loci are unique, and encode components of the sterol biosynthesis pathway (Schrick et al. 2000, Souter et at. 2002). Various patterning processes are disrupted in hydra mutants (Topping et at. 1997), and bulk sterol profiles are altered (Schrick et at. 2000, Souter et al. 2002). The mutants show heightened responses to auxin, and their phenotype is partly ameliorated by inhibition of ethylene signalling (Souter et al. 2002, 2004, He et al. 2003). Although much previous attention has been given to the analysis of their phenotype, the precise basis of the pleiotropic defects seen in the hydra mutants have not been attributed to any single phenomenon.This thesis examines the hydra mutants' body patterning and morphology, and aims to test the hypothesis that hydra mutants are defective in pattern coordination across the radial axis. The basis of phenotypic rescue through reduced ethylene perception, as conveyed by the ethylene insensitive2 (ein2) mutation (Alonso et al. 1999), is also examined using anatomical and transgenic markers of pattern definition and phytohormone signalling response. Mutants at the hydra loci have a substantial inter-sibling variability, including duplication or dissociation of the longitudinal axis. Reporter activities of the HYDRA 1 (HYD1) promoter implies an association of gene activity with stipules, and functional epidermal cells and ground tissue in both root and shoot tissues at the point of cell differentiation. Reporter expression defines a radial gradient across the root longitudinal axis which is maximal in thedifferentiation zone. All cell types highlighted by pHYD1 GUS activity sow anomalous cellular patterning in the root and rosette of hydra mutant seedlings, although pattern definition in lateral organs of the inflorescence stem appear relatively normal. Tissues of the hydra embryo and vegetative rosette have ectopic cell division activity; this persists in cotyledons beyond the point where wild-type cotyledon development has ceased Reduced ethylene perception via ein2 appears to confer a partial rescue of the hydra phenotype by facilitating an earlier transition from cell division to cell fate commitment, thus allowing greater coordination between cells in longitudinal cell files. This phenomenon may be attributable to enhanced auxin transport. In contrast, shoot dorsiventral cues are variably skewed or reversed, correlating with a loss of stipular function, in a manner independent of ethylene signalling. Other phytohormone signalling systems, as revealed by reporter constructs for auxin, cytokinin and gibberellin responsive genes, show a varied activity between seedlings. All of these responses appear anomalous in hydra single mutants, some with distinct differences between the two mutant sibling populations. These responses are partly modulated by ein2 in the hydra-ein2 double mutants, although ein2 itself has little or no effect on reporter activity. In particular the distinctive differences in cytokinin positional response between the two hydra mutants are abolished by the presence of ein2. HYDRA gene activity appears to modulate radial patterning and differentiation associated processes. The mutant shoot phenotypes suggest a role for sterolsin the definition of organ lateral boundaries and coordinated centrolateral expansion in flattened organs. In the mutant root, the control of the transition from division to differentiation in cortex cells is disrupted in hydra and may reflect a disrupted phosphate perception. As HYDRA gene activity is associated specifically with functional cells in the epidermis, this suggests that sterols may activate a mechanism for the timed differentiation of 'target cells'. Models are proposed to integrate the HYDRA gene expression data and the hydra mutant phenotype into a functional scheme of plant development.
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Joffrion, Tiffany Michelle. "Sterol biosynthesis and sterol uptake in the fungal pathogen Pneumocystis carinii." University of Cincinnati / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1267556286.
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Kroon, Paul Anthony. "Regulation of phytosterol and phytoalexin biosynthesis in plant tissue cultures." Thesis, University of Hull, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262429.
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Parkin, Edward T. "Regulation of phosphatidylcholine biosynthesis in Apium graveolens." Thesis, University of Central Lancashire, 1995. http://clok.uclan.ac.uk/20021/.
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When grown in the presence of the sterol biosynthesis inhibitor, paclobutrazol, suspension cultures of Apium graveolens (celery) accumulate substantial amounts of I 4a-methylsterols, at the expense of 4-demethylsterols. These changes have been correlated with reduced synthesis of phosphatidylcholine (PC) via the CDP-base pathway (Roiph & Goad, 1991). It was subsequently proposed that changes in the membrane sterol composition of plant cells may regulate the activity of CTP: cholinephosphate cytidylyltransferase (CT), the rate-determining enzyme of this pathway (Kinney & Moore, 1989). In preliminary studies, the membrane-associated form of CT in A.graveolens, was found to exhibit optimal activity at pH 7.7, in the presence of 8.0 mM CTP and 3.5 mM Mg2t Microsomal membrane fractions, in which a large proportion of CT activity was found to reside, were analysed in terms of lipid composition. The predominant phospholipid in such membranes, PC, constituted approximately 70% of the total phospholipid content. Other, more minor constituents, included phosphatidylethanolamine (PE), phosphatidylglycerol (PU), phosphatidylinositol (P1), phosphatidylserine (PS), and phosphatidic acid (PA). All phospholipids present in A.graveolens were found to be rich in linoleate (18:2) and palmitate (16:0). Lesser amounts of stearate (18:0), oleate (18:1), and a-linolenate (a- 18:3), were also present. The major phytosterols in microsomes were identified as campesterol, stigmasterol, sitosterol, and isoflicosterol, with trace amounts of cholesterol and 24-methylene cholesterol. The sterol biosynthesis inhibitors, miconazole, terbinafine, fenpropimorph, and tomatidine, proved to be useflul tools in the manipulation of membrane sterol composition in suspension cultures of A.graveolens. Treatment with these inhibitors caused significant alterations in lipid composition with corresponding changes in the activity of membrane-associated CT. Terbinaflne and fenpropimorph caused a large increase in the stigmasterol/sitosterol ratio of cells with a concomitant stimulation of CT activity. The latter compound also resulted in the accumulation of various 9$, 19- cyclopropyl sterols. Similarly, the azasterol inhibitor, tomatidine, resulted in an enhancement of CT activity, but with very lift le change in the stigmasterol/sitosterol ratio of cells. Conversely, miconazole resulted in a decline in the stigmasterol/sitosterol ratio, corresponding to lower membrane-associated CT activity. The latter inhibitor also caused an accumulation of oleoyl residues in the PC fraction of cells, suggesting an inhibition of A 1 2-desaturase activity. Radiolabelling studies with [3IflS-adenosyl-L-methionine revealed a degree of coordinate regulation between the CDP-base and methyltransferase pathways of PC biosynthesis. Consequently, despite changes in CT activity, levels of phospholipid in most inhibitor-treated cultures remained relatively constant. Supplementation of miconazole-treated cultures with free fatty acids partially overcame the cytostatic nature of the azole inhibitor, with a concomitant reactivation of CT. Mono- and diunsaturated fatty acids were found to be the most effective compounds in this respect. The addition of stigmasterol or sitosterol to miconazoletreated cultures also resulted in partial growth restoration and reactivation of membrane-bound CT.
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Mweetwa, Alice Mutiti. "Biosynthesis of Steroidal Glycoakaloids in Solanum chacoense Bitter." Diss., Virginia Tech, 2009. http://hdl.handle.net/10919/28572.
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Steroidal glycoalkaloids (SGAs) are secondary metabolites produced by approximately 350 species in the Solanaceae family. SGAs are reported to be important for pest resistance and flavor enhancement at low concentrations but are toxic to humans and other mammals at high concentrations. Studies on sterol / SGA biosynthesis have implicated squalene synthase as a key regulatory enzyme because it catalyzes an irreversible step from the mevalonic acid pathway. However, the regulatory mechanisms of squalene synthase are not yet known. A study was conducted to elucidate the distribution pattern of SGAs and to clone the squalene synthase gene in order to determine a relationship between SGAs and gene expression levels. Solanum chacoense, a wild potato species was used as a model plant from which tissues were harvested at specified developmental stages and analyzed for SGA content. The results from the SGA analysis suggest a qualitative and quantitative tissue- and age-dependent accumulation of SGAs. Regenerative tissues such as, axiliary shoots, flowers and floral buds had the highest levels of 88, 49 and 63 µmole/g DW, respectively. The roots, stems and tubers showed the lowest amounts of SGAs of 1 to 8, 5 to 15 and 7 to 15 µmole/g DW, respectively. Stolons and tubers accumulated higher amounts of α-chaconine (59 to 67%) than α-solanine (61 to 64%) at all developmental stages analyzed. On the other hand, in young expanding, fully expanded, and old senescing leaves where leptine and leptinines tend to dominate, α-solanine and α-chaconine together accounted for only 8 to 15%, 7 to 15%, and 8 to 45%, respectively. Plant organs that showed the highest biosynthetic activity for SGA production also had high levels of transcripts coding for genes of isoprenoid biosynthesis. The results from the cloning and characterization of squalene synthase suggest that the cloned cDNA fragment is a putative S. chacoense squalene synthase gene with an open reading frame / predicted protein precursor of 411 amino acids. The cloned cDNA has high similarity (68-100%) to known plant squalene synthase genes and contains six deduced peptide domains observed in other species. The 3â untranslated regions of floral buds, young leaves (early vegetative stage), and fully expanded leaves (anthesis) were different in length with, 249, 335, and 202 nucleotides, respectively. The Southern blot analysis suggests a single copy gene although the existence of a gene family cannot be ruled out.Ph. D.
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RONDET, SABINE. "Biosynthese des sterols : 4-carboxy-sterol decarboxylases de plante superieure et de levure ; identification, caracterisation et purification." Université Louis Pasteur (Strasbourg) (1971-2008), 1998. http://www.theses.fr/1998STR13225.
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La voie de biosynthese des sterols comporte deux etapes de demethylation en c4. Le systeme multienzymatique catalysant ce processus comprend au moins trois enzymes distinctes : la 4-methylsterol oxydase (4mo), la 4-carboxysterol decarboxylase (4cd) et la 3-ceto steroide oxydoreductase (3 cor). Nous avons pu, pour la premiere fois, identifier la 4cd de plante superieure et de levure dans des microsomes de zea mays et de saccharomyces cerevisiae, apres synthese de differents substrats et identification rigoureuse du produit de reaction, a savoir un 3-cetosteroide decarboxyle. Nous avons ensuite mis au point un test enzymatique operationnel et fiable, ce qui nous a permis d'etablir les parametres enzymologiques de la reaction. Les resultats indiquent notamment que l'etape de decarboxylation n'est pas limitante dans le processus global de demethylation des sterols en c4. Le mode d'action de la 4cd s'apparente a celui d'une 3-hydroxysterol deshydrogenase dependante de nad(p) -, nad + etant beaucoup plus efficace que nadp +. De plus, nous avons montre que la reaction catalysee par la 4cd est independante de l'oxygene moleculaire, ce qui indique l'existence de deux phases distinctes dans le processus de demethylation en c4, a savoir : une phase strictement dependante de l'oxygene catalysee par la 4mo, suivie d'une phase independante de l'oxygene, catalysee par la 4cd et la 3cor. La recherche d'inhibiteurs du systeme de demethylation en c4 nous a conduits a l'obtention de deux inhibiteurs efficaces de la 4mo et de la 4cd de mais respectivement. Nous avons entrepris la purification de la 4cd de mais et nous avons obtenu apres trois etapes de chromatographie (echange d'anions, affinite puis exclusion) un taux de purification de 300 a 500 fois, ce qui permet d'envisager le microsequencage de la proteine ou la production d'anticorps specifiques, dans l'optique du clonage du gene correspondant.
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Chen, Zhenbang. "Biosynthesis and regulation of Steroidal Alkaloids in Solanum Chacoense /." Connect to resource, 1999. http://rave.ohiolink.edu/etdc/view.cgi?acc%5Fnum=osu1250273569.
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Chrisp, P. "Novel azasterol antifungal agents from microorganisms." Thesis, University of Nottingham, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.380145.
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Spike, R. C. "The hamster harderian gland : Regulation of morphology and porphyrin biosynthesis by gonadal steroids." Thesis, University of Glasgow, 1986. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.383239.
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Erlandsson, Maria. "Imaging of Enzymes in the Steroid Biosynthetic Pathway : Synthesis of 18F-Labelled Tracers." Doctoral thesis, Uppsala universitet, Organisk kemi, 2009. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-89177.
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This thesis deals with the synthesis and development of 18F-labelled alkyl etomidate and vorozole analogues, and their use as positron emission tomography (PET) tracers for the imaging of the steroid enzymes 11β-hydroxylase and aromatase. Two synthetic 18F-labelling approaches to the etomidate and vorozole analogues were developed, and the analogues were evaluated in some biological assays. The two-step labelling method was used to synthesise many compounds for biological evaluation. In the first step, a 18F-labelled intermediate based on a ditosylate or a halogenated diethyl ether was synthesised and used directly in the next alkylation step. The decay-corrected (d.c.) radiochemical yield was higher compared to other known two-step labelling methods. Once an appropriate candidate has been chosen for clinical evaluation, a one-step labelling method will be more suitable. We therefore developed a method based on precursors that had leaving groups at the end of their alkyl chains, and used these directly in the 18F-labelling synthesis. The one-step 18F-labelling synthesis required less reaction time and produced higher specific radioactivity and d.c. radiochemical yield than our two-step synthesis. With microwave heating, the reaction time was reduced to seconds and the d.c. radiochemical yield was better than that obtained with conventional heating. The one-step synthesis simplified the technical handling by allowing the tracer syntheses to be automated on the TRACERLab FXFN.
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Arnqvist, Lisa. "Plant sterol metabolism with emphasis on glycoalkaloid biosynthesis in potato /." Uppsala : Dept. of Plant Biology and Forest Genetics, Swedish University of Agricultural Sciences, 2007. http://epsilon.slu.se/2007128.pdf.
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Blanc, Mathieu. "Sterol biosynthesis pathway is part of the interferon host defence response." Thesis, University of Edinburgh, 2011. http://hdl.handle.net/1842/5556.
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Recently, cholesterol metabolism has been shown to modulate the infection of several viruses and there is growing evidence that inflammatory response to infection also modulates lipid metabolism. However little is known about the role of inflammatory processes in modulating lipid metabolism and their consequences for the viral infection. This study investigates host-lipid viral interaction pathways using mouse cytomegalovirus, a large double-stranded DNA genome, which represents one of the few models for a natural infection of its natural host. In this study, transcriptomic and lipidomic profiling of macrophages shows that there is a specific coordinated regulation of the sterol pathways upon viral infection or treatment with IFNγ or β (but not TNFα, IL1β or IL6) resulting in the decrease of free cellular cholesterol. Furthermore, we show that pharmacological and RNAi inhibition of the sterol pathway augments protection against infection in vitro and in vivo and we identified that the prenylation branch of the sterol metabolic network was involved in the protective response. Finally, we show that genetic knock out of IFNβ results in a partial reduction while genetic knock out of Ifnar1 completely abolishes the reduction of the sterol biosynthetic activity upon infection. Overall these results support a role for part of the sterol metabolic network in protective immunity and show that type 1 IFN signalling is both necessary and sufficient for reducing the sterol metabolic network upon infection; thereby linking the sterol pathway with IFN defence responses.
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Ward, Patrick John. "Development of Steroidal Inhibitors of Cytochrome P450-Dependent Androgen and Estrogen Biosynthesis /." The Ohio State University, 1996. http://rave.ohiolink.edu/etdc/view?acc_num=osu1487935125882057.
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Schuler, Gerhard. "Plazentare Steroide beim Rind Biosynthese und Beziehungen zu Wachstum und Differenzierung der Planzentome /." [S.l.] : [s.n.], 2000. http://deposit.ddb.de/cgi-bin/dokserv?idn=963930478.
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Rasheed, Nabeela. "The effects of sterol biosynthesis inhibitors on the lipid composition of Apium graveolens." Thesis, University of Liverpool, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385160.
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Alkuwayti, Mayyadah. "The role of peroxisomes in sterol biosynthesis by the cellular slime mould Dictyostelium discoideum." Thesis, University of Sheffield, 2014. http://etheses.whiterose.ac.uk/7085/.
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In eukaryotic cells, the mevalonate pathway of isoprenoid biosynthesis provides the cell with essential precursors for several cellular processes. For example, one product, FDP (farnesyl diphosphate) is a fundamental precursor for sterol biosynthesis and it is also used for protein prenylation. In the slime mould Dictyostelium discoideum some of the mevalonate pathway enzymes possess a peroxisomal targeting signal. This suggested that part of the mevalonate pathway may take place in the peroxisomes. In this study, the intracellular locations of the mevalonate pathway enzymes were investigated by transforming D. discoideum amoebae to express each enzyme as a fusion protein with either GFP (green fluorescent protein) or mRFP (monomeric red fluorescent protein). It was found that three of the mevalonate pathway enzymes are peroxisomal: 3-hydroxy-3-methylglutaryl-coenzyme A synthase isozyme B, phosphomevalonate kinase and farnesyl diphosphate synthase. HMG-CoA reductase is associated with the endoplasmic reticulum and the other four enzymes of the mevalonate pathway were most likely to be in the cytosol: HMG-CoA synthase isozyme A, mevalonate kinase, diphosphomevalonate decarboxylase and IDP-isomerase. The intracellular location of the first five enzymes involved in sterol biosynthesis from farnesyl diphosphate was also identified by using the GFP or mRFP tagged enzyme approach. Some of these enzymes possess a strong peroxisomal targeting signal type 1 (PTS1). It was shown that the first four enzymes of the pathway: squalene synthase, squalene epoxidase, oxidosqualene cyclase and cycloartenol -C-24-methyltransferase are peroxisomal whereas the two isozymes of the fifth enzyme, methylsterol monooxygenase, are associated with the endoplasmic reticulum. It was also demonstrated that the first four enzymes on the sterol biosynthesis pathway are strongly associated with the peroxisomal membrane. However, the putative PTS1 present at the C-terminus of squalene synthase, oxidosqualene cyclase and cycloartenol-C-24-methyltransferase would imply that each of these enzymes should be a peroxisomal matrix protein. We therefore investigated whether the putative PTS1s are involved in directing these three enzymes into the peroxisomes. It was found that squalene synthase was largely peroxisomal even when its PTS1 was absent but the PTS1 in oxidosqualene synthase and cycloartenol-C-24-methyltransferase was essential for entry of these enzymes into peroxisomes. It appears that the sterol biosynthesis in D. discoideum is unusual since the enzymes squalene synthase, squalene epoxidase, oxidosqualene cyclase and cycloartenol-C-24-methyltransferase are accumulated in the peroxisomes whereas in all other organisms studied they are in the endoplasmic reticulum.
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Tronik, Le Roux Diana. "Regulation genetique et hormonale de la synthese de renine et de la proteine smr1 chez la souris et le rat." Paris 7, 1988. http://www.theses.fr/1988PA077163.
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Biosynthese et expression genique de renin dans la glande sousmaxillaire. Caracterisation d'une proteine smr1 tres abondante chez le rat male et absente chez la femelle. Les proteines de la glande sousmaxillaire du rat ne sont pas homologues de celles de la souris
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Hsieh, Wei Yuan. "Functional characterisation of the host sterol metabolic network in the interferon antiviral response." Thesis, University of Edinburgh, 2015. http://hdl.handle.net/1842/16187.
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Sterols play many important roles in physiology, including maintaining cell membrane integrity, and producing vitamin D and steroid hormones. Recent studies implicate sterol metabolism in the host innate immune response. Previous work, based on transcriptional profiling studies of mouse cytomegalovirus (MCMV) infection of primary bone-marrow-derived macrophages (BMDM, MΦ), uncovered a previously uncharacterized role of interferon in regulating the cholesterol pathway. Notably, Toll-like receptor (TLR) induced interferon modulates the suppression of SREBP2 (Sterol Regulatory Element-Binding Protein 2) activation, the master transcription factor for sterol biosynthesis. This finding resulted in the downregulation of the sterol biosynthesis pathway. However, how interferon is molecularly linked to sterol metabolism, and what part of the pathway mediates the antiviral effect remains unknown. The central hypothesis of the thesis is that the antiviral effect of interferon is in part mediated by secondary sterol metabolites and the dependency of viral replication on the host mevalonate branch of the sterol biosynthesis pathway. To test this hypothesis, my studies have examined the components of the host sterol pathway and their respective roles in influencing viral replication. Paradigmatically, I used MCMV and BMDM to explore the host- metabolic-virus interactions. Specifically, my findings address the question of how MCMV replication depends on the sterol biosynthesis pathway, and how the pathway is modulated by interferon as an antiviral response. In Chapter 2, the importance of the sterol biosynthesis pathway for viral replication was investigated using a combination of gene silencing and pharmacological inhibitors. These studies demonstrated that resistance to viral infection through suppressing the cholesterol pathway is not due to a requirement of the virus for cholesterol itself, but instead involves the mevalonate-isoprenoid arm of the pathway. This branch of the pathway chemically links lipids to specific host proteins (protein prenylation). These results suggest a new role for the mevalonate arm during viral infection. In Chapter 3, I examined what part of the sterol pathway mediates the antiviral effects. Oxysterols are natural modulators of sterol biosynthesis, and are produced by the oxidation of cholesterol by the enzyme cholesterol hydroxylase. Oxysterol suppression of SREBP2 activation leads to transcriptional repression of the sterol biosynthesis pathway. Additionally, oxysterols also modulate cholesterol homeostasis through cholesterol efflux. My studies led to identifing cholesterol-25-hydroxylase (Ch25h) as an interferon-stimulated gene (ISG). CH25H oxidizes cholesterol to produce a soluble oxysterol metabolite, 25-hydroxycholesterol (25-HC). Treatment of cells with 25-HC resulted in antiviral effects against MCMV and MHV-68. 25-HC was found to have no effects on MCMV entry into the host cell, but rather mediated inhibition of viral gene transcription. In addition, 25-HC-specific antiviral effect partially involved the suppression of the isoprenoid pathway, rather than cholesterol efflux. This work uncovered a physiological role for 25-HC as a sterol-lipid effector of an innate immune pathway. The antiviral activity of 25-HC in a lipid replete condition was found to occur at a concentration higher than the concentration required to inhibit SREBP2 activation. This implies that the antiviral effects of 25-HC is independent of SREBP2 in sterol replete conditions. Conversely, the antiviral action of 25-HC was signifi enhanced in cells under sterol-depleted conditions, suggesting that the antiviral effect of 25- HC is likely mediated through multiple processes involving SREBP2 dependent and independent mechanisms. These sterol dependent and independent mechanisms are examined in Chapter 4, using pathway expression profiling and pharmacological synergy studies. These studies showed that 25-HC suppression of the isoprenoid synthetic pathway is crucial in controlling infection, but also highlighted that other 25-HC dependent antiviral mechanisms are likely to exist. The inhibition of the mevalonate-isoprenoid arm by statins and 25-HC clearly demonstrated that MCMV replication dependents on protein prenylation. Chapter 5 investigation showed that either chemical inhibition of geranylgeranylation of host proteins or limiting mevalonate production led to restriction of MCMV replication. Importantly, through a series of systematic loss of function siRNA screenings demonstrated that specific host RabGTPases mediating vesicular transport pathways play vital roles in the replication and the assembly of the virus. This finding provides new mechanistic insights in to the dependency of cytomegalovirus replication on the host cell trafficking pathways and lays the groundwork for further definition of this important aspect of host-viral interactions. In summary, the overall findings of this research support the original hypothesis, by highlighting the importance of the host mevalonate-isoprenoid pathway, and provide further definition of the mechanisms and components linking sterol metabolism with interferon mediated antiviral effect.
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Al-Hejjaj, Murtakab. "Investigations of the role of peroxisomes in sterol biosynthesis in the slime mould Dictyostelium discoideum." Thesis, University of Sheffield, 2017. http://etheses.whiterose.ac.uk/19025/.
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Dictyostelium discoideum is a good model organism to study a variety of cellular processes. Its complete genome sequence is known (dictybase.org). It has a unique life style, with motile unicellular and multicellular stages, and multiple cell types (Annesley and Fisher 2009). It is widely used to study chemotactic motility and cytoskeletal dynamics. It is also used for studying molecular pathogenesis and treatment of human disease. Furthermore, since Dictyostelium cells readily take up drugs, it has led to identification of drug targets. For instance, farnesyl diphosphate synthase was found, by use of D. discoideum, to be the primary target of bisphosphonate drugs that are widely used to prevent and treat osteoporosis. A major challenge with this organism is the difficulty of making targeted mutations by homologous recombination. It is difficult to generate targeting constructs because of the high AT contents (77.4%) of its genome. Introduction of the Clustered Regularly Interspaced Short Palindromic Repeats system (CRISPR) into D. discoideum for obtaining gene knockouts would therefore be potentially most helpful and here I report on our progress in setting this up. All previous investigations of the intracellular location of the first four enzymes involved in sterol biosynthesis from farnesyl diphosphate (FDP) have found that they locate to the ER membrane in eukaryotic cells. However, we provide strong evidence that these enzymes are peroxisomal in D. discoideum. The first step in the pathway is catalysed by squalene synthase SQS. Surprisingly, (DdSQS) contains a typical peroxisomal targeting signal type 1 (PTS1). All known PTS1-containing proteins are localized to the peroxisomal matrix whereas membrane proteins use a different pathway. However, we found that DdSQS behaves as a membrane protein. Interestingly, as in other organisms, the DdSQS has a C-terminal amino acid sequence potentially forming a hydrophobic helix but which in D. discoideum is located immediately upstream of the PTS1. Deletion of this helix does not affect peroxisomal targeting but does affect DdSQS association with the membrane and may therefore serve as a tail anchor. Furthermore, the helix plays an important role in forming a SQS homodimer. SQS is the first example of a peroxisomal membrane protein that makes use of the PTS1 pathway for its localization. We have shown that the first four enzymes of sterol biosynthesis from FDP are associated with the peroxisomal membrane by using structured illumination microscopy. This is a relatively new technique that allows imaging beyond the resolution limit for light microscopy. Furthermore, the topology of the enzymes with respect to the peroxisomal membrane was experimentally determined. We provide a model of how sterol biosynthesis from FDP takes place in the peroxisomes of D. discoideum.
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Linscott, Kristin Brooke. "DISCOVERING A NOVEL ANTIFUNGAL TARGET IN DOWNSTREAM STEROL BIOSYNTHESIS USING A SQUALENE SYNTHASE FUNCTIONAL MOTIF." UKnowledge, 2017. http://uknowledge.uky.edu/biochem_etds/33.
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The sterol biosynthetic pathway is essential for growth of all eukaryotic cells and the main target of antifungal agents. The emergence of resistance to these antifungals in an already ill patient population indicates a need to develop drugs that have a broad spectrum of activity among pathogenic fungi and have minimal patient toxicity. Squalene synthase is the first committed step in the sterol pathway and has been studied intensively for development of antifungal agents. While the overall architecture of this enzyme is identical throughout eukaryotes, it was shown that plant and animal genes cannot complement a squalene synthase knockout mutation in yeast unless the carboxy-terminal domain is swapped for one of fungal origin. This implies that there is a component of the fungal carboxy-terminal domain that is responsible for the complementation phenotype and that is unique to the fungal kingdom of life.
To determine the role of the carboxy-terminal domain of squalene synthase in the sterol pathway, we used the yeast Saccharomyces cerevisiae with a squalene synthase knockout mutation and expressed squalene synthases originating from fungi, plants, and animals. In contrast to previous observations, all enzymes tested could partially complement the knockout mutation when the genes were weakly expressed. When induced, non-fungal squalene synthases could not complement the knockout mutation and instead led to the accumulation of carboxysterol intermediates, suggesting an interaction between squalene synthase and the downstream sterol C4-decarboxylase. Overexpression of a sterol C4-decarboxylase from any kingdom of life both decreased the accumulation of carboxysterol intermediates and allowed non-fungal squalene synthases to complement the squalene synthase knockout mutation.
Using chimeric squalene synthases from each kingdom of life, the motif in the C-terminal domain responsible for preventing this toxicity was mapped to a kingdom-specific 26-amino acid hinge motif adjacent to the catalytic domain. Furthermore, over-expression of the carboxy-terminal domain alone containing a hinge motif from fungi, not from animals or plants, led to growth inhibition of wild-type yeast. Since this hinge region is unique to and highly conserved within each kingdom of life, this data provides evidence for the development of an antifungal therapeutic as well as for tools to develop an understanding of triterpene catalytic activity and identify similar motifs in other biosynthetic pathways.
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Hubler, Zita. "Enhancing Oligodendrocyte Formation via Inhibition of the Cholesterol Biosynthesis Pathway." Case Western Reserve University School of Graduate Studies / OhioLINK, 2020. http://rave.ohiolink.edu/etdc/view?acc_num=case1595612178572819.
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Souidi, Maâmar. "Modulation de trois activites enzymatiques de la biosynthese des acides biliaires, la cholesterol 7 -hydroxylase, la sterol 27-hydroxylase et l'oxysterol 7 -hydroxylase, par differents steroides chez le hamster." Paris 11, 1999. http://www.theses.fr/1999PA112290.
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La biosynthese des acides biliaires est caracterisee par deux voies metaboliques. La voie neutre est initiee par la cholesterol 7-hydroxylase (c7-ohase) qui transforme le cholesterol en 7-oh-cholesterol et conduit a la production des acides cholique (c) et chenodesoxycholique (cdc). La seconde voie, dite acide, est initiee par la sterol 27-hydroxylase (s27-ohase) qui transforme le cholesterol en 27-oh-cholesterol. Ce compose est metabolise par l'oxysterol 7-hydroxylase (os7-ohase) en 7, 27-dioh-cholesterol et conduit a la formation de cdc. Apres avoir ameliore le dosage des activites de ces enzymes chez le hamster par l'utilisation de l'hydroxypropyl--cyclodextrine comme moyen de solubilisation et de transport du substrat a l'enzyme, nous avons teste l'effet, in vitro, de steroides sur ces activites. Le 7-oh-cholesterol inhibe les trois activites tandis que le 25-oh- et le 27-oh-cholesterol sont sans effet sur la c7-ohase et de la s27-ohase. Le cholesterol inhibe l'activite de l'os7-ohase. Le cholesterol et ses derives peuvent donc moduler l'activite de ces enzymes. De plus, nous avons montre que l'epicoprostanol et la cyclosporine a inhibaient l'activite de la s27-ohase et de l'os7-ohase. Cet effet pourrait etre du a la presence d'une chaine aliphatique commune a ces deux composes. Nous avons ensuite etudie les effets in vivo de regimes contenant 0,1% d'epicoprostanol (e), de 25-oh-cholesterol (s25), de 27-oh-cholesterol (s27) ou d'acide hyodesoxycholique (h) sur les activites des trois enzymes. Nous avons confirme l'inhibition specifique de l'activite de la s27-ohase par e, deja observee in vitro, et montre une inhibition de l'activite de la c7-ohase et de l'os7-ohase par le s27 alors que le s25 n'affecte pas ces activites. La difference d'action de ces oxysterols pourrait s'expliquer par leur capacite d'orienter differemment la synthese des acides biliaires, le 27-oh-cholesterol conduisant a la formation de cdc (hydrophobe) et le 25-oh-cholesterol a celle d'acide cholique (neutre). Enfin, nous avons montre l'inhibition de l'activite de la s27-ohase par le regime h (hydrophile). Ces resultats suggerent que la voie neutre est sensible aux acides biliaires hydrophobes tandis que la voie acide serait influencee par les acides biliaires hydrophiles.
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Müller, Christoph. "Charakterisierung von Sterol-Biosynthese-Inhibitoren und Entwicklung von Methoden für die moderne Spurenanalytik." Diss., Ludwig-Maximilians-Universität München, 2013. http://nbn-resolving.de/urn:nbn:de:bvb:19-168544.
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Die Entwicklung und die Erforschung von Sterol-Biosynthese-Inhibitoren ist ein wichtiges Thema in der pharmazeutischen Chemie.
Durch die Verwendung eines Ganzzell-Assays konnte eine Reihe von Inhibitoren im Post-Lanosterol-Abschnitt der Cholesterol-Biosynthese charakterisiert werden. Darunter waren Inhibitoren der Oxidosqualencylase, der delta24-Reduktase, der delta8/7-Isomerase und der 7-Dehydrocholesterolreduktase. Diese Substanzen zeichneten sich durch zum Teil nanomolare IC50-Werte, gemessen an der Gesamt-Cholesterol-Neubildung aus, sowie durch eine hohe Selektivität. Die Verbindungen könnten als molekulares Werkzeug zur Erforschung von Cholesterol-Biosynthese induzierten Pathogenesen eingesetzt werden oder aber als Adjuvans in der Chemotherapie.
Durch die Neuentwicklung eines Ganzzell-Screening-Assays für den Post-Lanosterol-Abschnitt der Ergosterol-Biosynthese war es nun auch möglich, Verbindungen auf ihre antimykotische Aktivität zu testen. Dabei konnte EMC120B12 als neuer Inhibitor der C14-Demethylase identifiziert werden. In Candida krusei bildeten sich unter dessen Zugabe bis dato unbekannte Sterole. Diese konnten als Derivate von 14-Methylergosta-8,24(28)-dien-3beta,6alpha-diol identifiziert werden. Ebenso wurde eine IC50-Wert-Bestimmung, gemessen an der Gesamt-Ergosterol-Neubildung durch Einbau von nicht-radioaktiven 13C-Acetat in Ergosterol etabliert.
Des Weiteren wurden neue Methoden für die moderne Spurenanalytik entwickelt. Das Kernstück dabei war die Entwicklung einer Methode zur Bestimmung von Nicotin und Coffein in Schokolade mittels Dampfraum-Festphasenmikroextraktion (HS-SPME) gekoppelt mit einem Gaschromatographie-Tandemmassenspektrie Gerät (GC-MS/MS). Dabei konnte zum ersten Mal Nicotin in Schokolade nachgewiesen werden (230-1590 ng/kg). Die gleichzeitige Mitbestimmung des bereits bekannten Inhaltsstoffes Coffein (420-2780 mg/kg) war trotz der hohen Konzentrationsunterschiede möglich.
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Zhang, Shuo. "Characterization and application of the fungal genes involved in the biosynthesis of polyunsaturated fatty acid and sterol." Kyoto University, 2006. http://hdl.handle.net/2433/136505.
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Kyoto University (京都大学)0048
新制・課程博士
博士(農学)
甲第12667号
農博第1590号
新制||農||934(附属図書館)
学位論文||H18||N4193(農学部図書室)
UT51-2006-U372
京都大学大学院農学研究科応用生命科学専攻
(主査)教授 清水 昌, 教授 喜多 恵子, 教授 阪井 康能
学位規則第4条第1項該当
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GRAUSEM, BERNARD. "Transformation de plantes avec des genes codant pour des enzymes de la biosynthese des sterols." Université Louis Pasteur (Strasbourg) (1971-2008), 1996. http://www.theses.fr/1996STR13115.
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Des protoplastes de tabac ont ete transformes par un adn-t contenant le gene cyp51a1 codant pour la lanosterol-14-demethylase de saccharomyces cerevisiae (enzyme homologue de l'obtusifoliol-14-demethylase de plante). Les lignees transgeniques exprimant la lanosterol-14-demethylase presentent une resistance a un triazole herbicide inhibiteur de l'obtusifoliol-14-demethylase. Le mecanisme de resistance mis en jeu provient du contournement de l'inhibition de l'obtusifoliol-14-demethylase par l'herbicide grace a l'expression de la lanosterol-14-demethylase de levure. En effet, cette derniere n'est pas affectee par l'inhibiteur et est en mesure de metaboliser le substrat de l'obtusifiliol-14-demethylase. La composition sterolique des genotypes resistants reflete une teneur en #5-sterols (sterols physiologiques de fin de chaine) proche de celle d'un genotype non traite par l'herbicide. Les genotypes temoins, par contre, accumulent des intermediaires biosynthetiques en presence de l'herbicide. Une autre partie du travail a consiste en la transformation de plantes d'arabidopsis thaliana avec le gene codant pour la cycloartenol synthase en orientation sens ou anti-sens dans le but de modifier la quantite de sterols des plantes ainsi generees. Certaines plantes transformees par ce gene en orientation sens presentent un phenotype biochimique inattendu, a savoir une accumulation de triterpenes pentacycliques (l' et la -amyrine) derivant de l'epoxyde de squalene. L'expression du gene codant pour la cycloartenol synthase en orientation anti-sens n'a pas donne de resultats concluants. Enfin, des tabacs ont ete transformees par le gene codant pour la lanosterol synthase de candida albicans ; le but etant de faire synthetiser a partir de l'epoxyde de squalene du lanosterol, sterol inexistant chez les plantes. Aucun transformant n'a fait apparaitre de phenotype biochimique particulier ; ce qui peut laisser envisager l'hypothese d'une toxicite du lanosterol ou de l'un de ses metabolites dans les plantes
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HUSSELSTEIN, TANIA. "Enzymes de la voie de biosynthese des sterols de plantes : clonages d'alleles sauvages et mutants." Université Louis Pasteur (Strasbourg) (1971-2008), 1998. http://www.theses.fr/1998STR13212.
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Le mutant stel d'arabidopsis thaliana, issu d'une mutagenese ems, se caracterise par l'accumulation de #7-sterols au detriment des #5-sterols accumules majoritairement dans les plantes sauvages. L'expression dans le mutant stel d'une #7-sterol-c5-desaturase sauvage d'arabidopsis thaliana, clonee par complementation fonctionnelle heterologue du mutant erg3 de saccharomyces cerevisiae, a permis de restaurer un phenotype sauvage apportant ainsi la preuve d'une deficience au niveau de l'etape de c5-desaturation chez ce mutant. Nous avons clone l'allele mute de la #7-sterol-c5 desaturase de la plante stel par une reaction de rtpcr a l'aide d'oligonucleotides deduits de la sequence sauvage et ainsi mis en evidence une mutation ponctuelle dans le phase ouverte de lecture de l'enzyme provoquant le remplacement d'une threonine par une isoleucine. Nous avons ensuite caracterise des alleles mutes de la #7-sterol-c5-desaturase, obtenus par mutagenese dirigee ou aleatoire, et ainsi identifie des amino acides indispensables pour une bonne activite catalytique de l'enzyme. Par complementation de fonction de mutants de levures ou par recherche de nouveaux sterols apres transformation de levures sauvages, nous avons egalement caracterise des alleles sauvages codant d'autres enzymes de la voie de biosynthese des phytosterols.
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Briot, Pascal. "Etudes in vivo et in vitro de la biosynthèse des œstrogènes chez la hase (Lepus europaeus)." Paris 6, 1986. http://www.theses.fr/1986PA066159.
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Etude sur le sang des veines périphériques, ovariennes, utérines au cave de femelles gestantes ou non gestantes, stimulées par PMSG ou non stimulées. In vitro étude sur tissus incubés (follicules, corps jaune, surrénale, endomètre ou placenta).
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Müller, Christoph Anton [Verfasser]. "Charakterisierung von Sterol-Biosynthese-Inhibitoren und Entwicklung von Methoden für die moderne Spurenanalytik / Christoph Anton Müller." München : Verlag Dr. Hut, 2014. http://d-nb.info/1052374522/34.
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Delarue, Catherine. "Contribution à l'étude des mécanismes de régulation de la stéroïdogénèse surrénalienne chez les amphibiens." Rouen, 1987. http://www.theses.fr/1987ROUES035.
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Mise en évidence du rôle physiologique de la sérotonine dans la régulation de la stéroïdogénèse par son identification par immunofluorescence et électrochimie dans les cellules chromaffines qui pourraient stimuler la stéroïdogénèse par régulation paracrine sous contrôle orthosympathique. Rôle des prostaglandines dans les mécanismes de couplage stimulus-sécrétion: les PG de la série E et la PG I2 peuvent être considérées comme des seconds messagers potentiels de l'angiotensine II et de l'acétylcholine
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Mbaya, Bonaventure. "Contribution a l'étude des mécanismes de régulation de la biosynthèse des sterols chez la levure saccharomyces cerevisiae." Poitiers, 1988. http://www.theses.fr/1988POIT2290.
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Duba, Nandipha. "Investigation of the link between drought-induced changes in the expression of a novel sterol biosynthesis gene and drought tolerance in soybean." University of the Western Cape, 2017. http://hdl.handle.net/11394/6338.
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Magister Scientiae - MSc (Biotechnology)Glycine max (soybean) is an important crop species globally as it is used as a protein-rich food and feed crop and as a source of oils used in the food and biofuel industry. However, the growth and yield of soybean is adversely affected by drought. Exposure of soybean to drought leads to accumulation of reactive oxygen species (ROS) and cell membrane instability. Sterols are membrane components that regulates membrane fluidity and permeability. Besides being major components of the cell membranes, sterols such as lanosterol appear to play a role in the regulation of ROS scavenging and some are precursors to brassinosteroids that act as signaling molecules with hormonal function that regulate growth, development and responses to abiotic stresses such as drought and salinity. In this study, the involvement of plant sterols, also known as phytosterols, in the regulation of soybean responses to drought stress was investigated in Glycine max by determining the effects of drought on the expression of a candidate lanosterol synthase gene (Glyma08g24160) and the content of a subset of phytosterols in soybean. The effects of inhibition of sterol synthesis on ROS production and on superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT) and dehydroascorbate reductase (DHAR) were investigated. The concentration of hydrogen peroxide (H2O2) as well as superoxide (O2-) increased in response to drought and sterol synthesis inhibition, however, O2- concentration and sterol contents declined under drought stress and sterol synthesis inhibition.