Biology Commons^™

Structural And Biochemical Studies Of The Carboxyltransferase Domain From Pyruvate Carboxylase, Adam David Lietzan

Dissertations (1934 -)

Pyruvate carboxylase (PC; E.C. 6.4.1.1), a multifunctional biotin-dependent enzyme, catalyzes the bicarbonate- and MgATP-dependent carboxylation of pyruvate to oxaloacetate. To complete the overall reaction, the tethered biotin prosthetic group must first gain access to the biotin carboxylase domain and become carboxylated, and then translocate to the carboxyltransferase (CT) domain where the carboxyl group is transferred from biotin to pyruvate. Kinetic analyses of PC have suggested that the spatially distinct reactions, which occur in the active sites of the BC and CT domains, are well coordinated. To gain insights into the molecular events necessary for coordinating catalysis in the CT domain, …

Impact Of Mtr4 Structural Domains On Its Enzymatic Activities, In The Regulation Of Nuclear Rna Turnover, Li Yan

Dissertations (1934 -)

RNA processing and turnover plays an important role in RNA maturation, metabolism and quality control, which contribute to gene regulation and cell health. The TRAMP complex, composed of an RNA binding protein Air2p, a poly-A polymerase Trf4p, and a RNA helicase Mtr4p, assist nuclear exosome-dependent RNA processing and degradation in Saccharomyces cerevisiae, like tRNAiMet turnover, 5'ETS degradation and rRNA processing. Mtr4p structure reveals a novel protruding arch domain, which contains the recognizable KOW domain and a stalk domain. Except for the two conserved RecA-like helicase domains, the helicase core contains two other structural domains, a winged helix that connects arch …

The Role Of Prka-Mediated Stimulation Of Fatty Acid Oxidation In The Regulation Of Meiotic Maturation In Mouse Oocytes, Deepa Valsangkar

Dissertations (1934 -)

Meiosis is a defining aspect of sexual reproduction and its outcome often determines reproductive success. In mammalian females, oocytes initiate meiosis in early embryonic stages but arrest in the late prophase of meiosis-I around the time of birth. They remain arrested until hormonal induction during reproductive cycles after puberty, and then resume meiosis until a second arrest at metaphase-II. The process of oocyte meiosis from the release of prophase arrest till the metaphase-II arrest is known as oocyte maturation. Meiotic arrest is a result of maintenance of elevated cAMP levels within the oocyte by its continuous production as well as …

Structural And Functional Studies Of Urea Amidolyase, Yi Lin

Dissertations (1934 -)

Urea amidolyase (UAL) is a key virulence factor that regulates the yeast to hyphae switch in the opportunistic pathogen, Candida albicans. UAL is a multi-domain enzyme with two enzyme activities: urea carboxylase (UC) and allophanate hydrolase (AH). UC is a biotin-dependent carboxylase that adds a carboxyl group to urea to make allophanate by the coordinated action of three domains. Allophanate is subsequently hydrolyzed into NH3 and CO2 in the AH domain. Studies on the structure and function of UAL may lead to treatments for systemic candidiasis and can serve to clarify the molecular basis for multi-functional swinging arm enzymes. In …

Coordination Of Primer Sugar Synthesis With O-Antigen Initiation In Rhizobium Etli Ce3, Tiezheng Li

Dissertations (1934 -)

All organisms synthesize amidosugars, such as N-acetylglucosamine (GlcNAc), and deoxysugars, such as fucose. They are found in important polysaccharides and glycoconjugates such as glycoproteins. N-acetylquinovosamine (QuiNAc) is both an amido- and a deoxy-sugar. It is found in many examples of an important prokaryotic glycoconjugate, the lipopolysaccharide (LPS) that coats the surface of Gram-negative bacteria. Like N-glycosylation of glycoproteins, LPS has a portion that is synthesized first on a polyprenyl lipid carrier and then transferred to the rest of the molecule. QuiNAc is believed to initiate the O-antigen portion of LPS of Rhizobium etli CE3. Genetic studies identified three genes, wreV, …

Cross-Bridge Mechanisms Of Skeletal Muscle Fatigue: Effects Of Hydrogen Ion, Inorganic Phosphate, And Age, Cassandra Rae Nelson

Dissertations (1934 -)

Intense muscle contraction induces high rates of glycolysis and ATP hydrolysis with resulting increases in inorganic phosphate (Pi) and H+, factors thought to induce fatigue by interfering with steps in the cross-bridge cycle. Force inhibition is less at physiological temperatures; thus the role of low pH in fatigue has been questioned. Effects of pH 6.2 and collective effects with 30 mM Pi on the pCa-force relationship were assessed in skinned fast and slow rat skeletal muscle fibers at low (15°C) and near-physiological temperatures (30°C). At Ca2+ levels characteristic of fatigue, low pH significantly depressed force at both temperatures and in …

Mechanism Of GabaB Receptor-Activated Increases In L-Type Calcium Current In The Neonatal Mammalian Hippocampus, Andrew S. Karls

Dissertations (1934 -)

Activation of the metabotropic GABA_B receptor has most commonly been demonstrated to produce inhibitory effects on neurons, including the attenuation of voltage-dependent calcium current. However, during the early neonatal period in mammalian development, activation of GABA_B receptors leads to an enhancement of calcium current through a specific class of calcium channels, termed L-type channels, (because they conduct Long-lasting current) . This response peaks at 7 days postnatal, and is only demonstrated in a subset of cells. In the work presented here, the signal transduction pathway of GABA_B receptor-mediated increase of L-type current is described.

GABA_B receptors …

Hypothalamic Pituitary Adenylate Cyclase-Activating Polypeptide: Impact On Energy Homeostasis And Glutamate Signaling, Jon Resch

Dissertations (1934 -)

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a member of the secretin-glucagon superfamily of peptide hormones, with homology to vasoactive intestinal polypeptide (VIP) and activity at both the VIP receptors and the PACAP specific PAC1 receptor (PAC1R). Abundantly expressed in the hypothalamus, PACAP was recently discovered to regulate energy balance when central injections produced hypophagia and increased metabolic rate. However, the neurocircuitry mediating these effects in the hypothalamus are poorly understood.

To characterize how hypothalamic PACAP signaling affects energy homeostasis we microinjected PACAP site-specifically into the hypothalamic paraventricular (PVN) and ventromedial nuclei (VMN) and examined feeding behavior and metabolism. PACAP injected …

Ventral Tegmental Area Regulation Of Stress-Induced Reinstatement Of Cocaine-Seeking Behavior, Jordan Michael Blacktop

Dissertations (1934 -)

No FDA approved medications currently exist for the prevention of drug craving, drug seeking, and relapse to cocaine use. Stress is a major factor in causing relapse in cocaine dependent individuals. Cocaine use is positively correlated with stress-induced craving and relapse outcomes. Corticotropin-releasing factor (CRF) is a 41-amino acid neuropeptide that plays an important role in the stress response and in the reinstatement rodent model of stress-induced relapse. CRF is released during stress in brain regions associated with the effects of drugs of abuse, notably the ventral tegmental area (VTA). This dissertation addresses key unknown mechanisms behind drug-induced neuroplasticity and …