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The Global ETD Search service is a free service for researchers
to find electronic theses and dissertations. This service is
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Networked Digital Library of Theses and Dissertations.
Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
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Showing 1 to 9 of 9 (0.059 seconds)| 1 |
Studies on enzymes involved in the biosynthesis of pterin cofactorsBaker, Stephen John January 1997 (has links)
No description available.
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Deoxyguanosine triphosphate, a possible target for reactive oxygen species-induced mutagenesisTassotto, Mary Lynn Benka 04 September 2002 (has links)
Intracellular dNTP pool sizes are highly asymmetric, with dGTP usually
comprising 5 to 10% of the sum of the dNTP pools. The work presented in this
dissertation addresses the question of whether the underrepresentation of dGTP is
related to its potential to be oxidized by reactive oxygen species. 8-oxo-guanine is
important in oxidative mutagenesis, and current evidence indicates that this lesion
arises in DNA partly through oxidation of dGTP, followed by incorporation of 8-oxo-dGTP
into DNA. The bacterial MutT protein and its mammalian homolog catalyze the
hydrolysis of 8-oxo-dGTP to 8-oxo-dGMP in vitro. It is a widely accepted premise
that the primary function of these enzymes is to remove 8-oxo-dGTP from the
nucleotide pool of cells so that it cannot be used as a substrate for DNA synthesis.
However, this model has been called into question by observations that some mutT
strains of E. coli display a mutator phenotype when grown anaerobically, and by
kinetic studies that showed 8-oxo-dGTP to be a poor DNA polymerase substrate.
In this study, the dNTP pools of mammalian cells cultured in varying oxygen
conditions were measured, with the expectation that the dGTP pool would expand
under low oxygen conditions if it were a target for damage by reactive oxygen species.
HeLa cells cultured in 2% 0��� showed no change in the dGTP pool when compared to
cells cultured in 20% 0���; however, in V79 cells, the dGTP pool did expand in 2% 0���.
This result was not specific to the dGTP pool, as pools of dATP and dTTP also
increased when V79 cells were cultured at 2% 0���. These results suggest that there may
be increased turnover of the dGTP pool when cells are cultured in high oxygen, but
these experiments did not address the reason for this oxygen-dependent change.
In order to determine whether 8-oxo-dGTP accumulates to levels that are
sufficient to cause mutagenesis in cells, an analytical method for the measurement of
8-oxo-dGTP from cell extracts was developed. By use of this method, which involves
reversed-phase high performance liquid chromatography coupled with electrochemical
detection, no 8-oxo-dGTP was detected in mutT E. coli cells, even when they were
cultured in the presence of H���0���. The estimated upper limit of 8-oxo-dGTP in these
cells is about 240 molecules per cell, which corresponds to an intracellular
concentration of approximately 0.34 ��M. When 8-oxo-dGTP was added at this
concentration to an in vitro DNA replication system in which replication errors could
be scored as mutations, along with the four normal dNTPs at their estimated
intracellular concentrations, there was no detectable effect on the frequency of
mutation. Therefore, the presence of 8-oxo-dGTP at physiologically relevant
concentrations does not appear to be significantly mutagenic. The results presented in
this dissertation suggest that the mechanism by which the MutT enzyme counteracts
mutagenesis should be reevaluated. / Graduation date: 2003
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Oxidative stress and the guanosine nucleotide triphosphate pool implications for a biomarker and mechanism of impaired cell function /Bolin, Celeste Maree. January 2008 (has links)
Thesis (Ph. D.)--University of Montana, 2008. / Title from title screen. Description based on contents viewed Aug. 19, 2008. Includes bibliographical references.
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Effector regulation domains on G[alpha]16 and their role in the activation of phospholipase C[Beta] and other effectors /Yu, Yan Mei. January 2004 (has links)
Thesis (M. Phil.)--Hong Kong University of Science and Technology, 2004. / Includes bibliographical references (leaves 94-103). Also available in electronic version. Access restricted to campus users.
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Ornithine decarboxylase:expression and regulation in rat brain and in transgenic miceKilpeläinen, P. (Pekka) 25 March 2002 (has links)
Abstract
Ornithine decarboxylase (EC 4.1.1. 17) is the first and the
rate-controlling
enzyme in polyamine biosynthesis. It decarboxylates L-ornithine to form diamine
putrescine. ODC activity in cells is strictly regulated and one of the central
elements of ODC regulation is an inhibitory protein called antizyme. Antizyme
binds to ODC, inhibits its activity and targets ODC for the proteasomal
degradation. Essentiality of polyamines for the normal cell growth and
proliferation is well known. Recently their roles in the regulation of several
classes of cation channels have been discovered. Some of these channels are
expressed abundantly in the brain, which has increased interest in the polyamine
metabolism in the central nervous system.
In this study guanosine 5'-triphosphate activatable ODC was detected in the
rat
brain lysates. This activation was more significant after antizyme was separated
from ODC. GTP-activatable ODC was more resistant to heat and displayed higher
Vmax than kidney ODC. Previously GTP-activatable ODC had
been found in mammalian tissues only in some tumors. ODC and antizyme expression
in brain was localized by in situ hybridization and
immunocytochemistry. Both proteins displayed wide and largely overlapping
expression patterns restricted to neurons. The proteins were localized
predominantly to cytoplasm at the most brain regions, but antizyme had a main
localization in nuclei in some regions of the brain. In addition, the role of one
of the most highly conserved regions in eukaryotic ODCs was studied using
site-directed mutagenesis. The aspartate-233 to valine mutation was made and
detected to increase Km values for the cofactor PLP and
the substrate L-ornithine as well as Ki value for the
inhibitor DFMO.
In another part of this study a transgenic mouse line expressing ODC under the
control of viral promotor was generated. The most significant changes in ODC
activity were detected in reproductive organs of male mice. The high number of
infertile transgenic males supported earlier reports about the importance of
balanced polyamine metabolism for spermatogenesis. Infertility of female mice was
increased as well, but the involvement of polyamines remained unproven.
Transgenic mice were prone to various pathological conditions such as
inflammations and tumour formation, which may be due to deregulated polyamine
metabolism.
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Studies towards a general method for attachment of a nuclear import signal. Stabilization of the m<sub>3</sub>G-Cap.Lindvall, Mattias January 2010 (has links)
<p>A synthetic pathway towards the cap-structure of 2,2,7-trimethylguanosine containing a methylene modified triphosphate bridge have been investigated. The modification to the triphosphate bridge is hoped to slow down cap degradation and give the connected oligunucleotide an increased lifetime. This could result in an better understanding of nuclear transport of oligonucleotides and could thereby helping to develop new treatments for different diseases. The synthesis relies on a coupling reaction between the 2,2,7-trimethylguanosine 5’phosphate and 2’-<em>O</em>-methyladenosine with a 5’-pyrophosphate where the central oxygen has been replaced by a methylene group. The reaction pathway consists of 9 steps of which 8 steps have been successfully performed. The last step, which includes a coupling reaction, was attempted but without successful identification and isolation of the cap-structure, and will need further attention. The reaction has been performed in a milligram scale with various yields.</p> / Presentation utförd
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Estimating the distribution and production of microplankton in a coastal upwelling front from the cellular content of guanosine-5 triphosphate and adenosine-5 triphosphateJori, Carol Diane. January 1981 (has links)
Thesis (M.S.)--Naval Postgraduate School, 1981. / Cover title. "September 1981." Includes bibliographical references (leaves 108-120).
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Studies towards a general method for attachment of a nuclear import signal. Stabilization of the m3G-Cap.Lindvall, Mattias January 2010 (has links)
A synthetic pathway towards the cap-structure of 2,2,7-trimethylguanosine containing a methylene modified triphosphate bridge have been investigated. The modification to the triphosphate bridge is hoped to slow down cap degradation and give the connected oligunucleotide an increased lifetime. This could result in an better understanding of nuclear transport of oligonucleotides and could thereby helping to develop new treatments for different diseases. The synthesis relies on a coupling reaction between the 2,2,7-trimethylguanosine 5’phosphate and 2’-O-methyladenosine with a 5’-pyrophosphate where the central oxygen has been replaced by a methylene group. The reaction pathway consists of 9 steps of which 8 steps have been successfully performed. The last step, which includes a coupling reaction, was attempted but without successful identification and isolation of the cap-structure, and will need further attention. The reaction has been performed in a milligram scale with various yields. / Presentation utförd
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Electrostaticanalisys the Ras active siteKhan, Abdul Kareem 05 March 2009 (has links)
La preorganització electrostàtica del centre actiu s'ha postulat com el mecanisme genèric de l'acció dels enzims. Així, alguns residus "estratègics" es disposarien per catalitzar reaccions interaccionant en una forma més forta amb l'estat de transició, baixant d'aquesta manera el valor de l'energia dactivació g cat. S'ha proposat que aquesta preorientació electrostática s'hauria de poder mostrar analitzant l'estabilitat electrostàtica de residus individuals en el centre actiu.Ras es una proteïna essencial de senyalització i actúa com un interruptor cel.lular. Les característiques estructurals de Ras en el seu estat actiu (ON) són diferents de les que té a l'estat inactiu (OFF). En aquesta tesi es duu a terme una anàlisi exhaustiva de l'estabilitat dels residus del centre actiu deRas en l'estat actiu i inactiu. / The electrostatic preorganization of the active site has been put forward as the general framework of action of enzymes. Thus, enzymes would position "strategic" residues in such a way to be prepared to catalyze reactions byinteracting in a stronger way with the transition state, in this way decreasing the activation energy g cat for the catalytic process. It has been proposed thatsuch electrostatic preorientation should be shown by analyzing the electrostatic stability of individual residues in the active site.Ras protein is an essential signaling molecule and functions as a switch in thecell. The structural features of the Ras protein in its active state (ON state) are different than those in its inactive state (OFF state). In this thesis, an exhaustive analysis of the stability of residues in the active and inactive Ras active site is performed.
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