Browsing by Subject "Fructose"
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Item Insight into a unique carbon resource partitioning mechanism in Aggregatibacter actinomycetemcomitans(2010-08) Brown, Stacie Anne, 1979-; Whiteley, Marvin; Meyer, Richard; Walker, James; McLean, RobertAggregatibacter actinomycetemcomitans is a Gram negative bacterium found exclusively in the mammalian oral cavity where it resides in the gingival crevice, the space between the tooth and gum tissue. Though it has historically been considered a common commensal organism, it is now appreciated that A. actinomycetemcomitans is an opportunistic pathogen associated with the diseases periodontitis and endocarditis. To cause infection, A. actinomycetemcomitans must interact and compete with neighboring bacteria for space and nutrients, though little is known about the physiology it employs within the gingival crevice. Using A. actinomycetemcomitans grown in a chemically defined medium containing carbon sources found in vivo, I use transcriptome analyses and growth studies to show that A. actinomycetemcomitans preferentially utilizes lactate over the phosphotransferase system (PTS) sugars glucose and fructose. Additionally, the presence of lactate or pyruvate inhibits the transport and metabolism of these sugars in a post-transcriptionally controlled process I have termed PTS substrate exclusion. Since lactate is an energetically inferior carbon source, PTS substrate exclusion appears to be a carbon resource partitioning mechanism that allows A. actinomycetemcomitans to avoid competition for energetically favorable sugars with other species, and I propose a model to describe this phenomenon. To begin to understand the mechanism of PTS substrate exclusion, I examine the first step of the proposed model by purifying and characterizing the L-lactate dehydrogenase (LctD) from A. actinomycetemcomitans. I demonstrate that, unlike other studied lactate dehydrogenases, the LctD from A. actinomycetemcomitans does not exhibit feedback inhibition in the presence of physiologically relevant concentrations of pyruvate, which supports my hypothesis that elevated intracellular pyruvate levels inhibit the PTS. The results of my studies provide insight into a new regulatory mechanism governing carbon utilization in this bacterium.Item Regulation of intestinal nutrient uptake by glucagon-like peptide-1 in rats(Texas Tech University, 1998-08) Shephard, David M.Glucagon-like peptide-1 (GLP-1) is a peptide derived from the prohormone proglucagon and is secreted primarily from the L-cells of the ileum. The major bioactive form of GLP-1 is truncated GLP-1 (tGLP-1). tGLP-1 is shortened by 6 amino acids from the N-terminus and has a C-terminal amidation. Food and water intake are both inhibited by tGLP-1, and its action as an incretin hormone (a hormone that stimulates insulin release in the presence of elevated blood glucose concentrations) is believed to be its most biologically important function. Nevertheless, many other functions for tGLP-1 have been proposed in many different tissues. Oxyntomodulin is co-secreted with tGLP-1 from the L-cells, and both peptides share sequence homology with glucagon. Moreover, both oxyntomodulin and glucagon increase active glucose transport across the brush-border membrane of the small intestine. Based on this information, I tested the hypothesis that tGLP-1 might also regulate intestinal nutrient uptake. Male Sprague-Dawley rats were infused with different doses of synthetic rat tGLP-1 transport rates of several representative nutrients (proline, alanine, glucose, and finctose) measured using an everted intestinal sleeve method. Proline and alanine transport were unaffected, and we were surprised to find that glucose uptake was either unaffected or slightly inhibited by the infusions. Equally surprising, however, was that fructose transport was stimulated strongly in the proximal intestine, and the animal's overall, daily capacity to transport fructose was also stimulated. These results along with the fact that the intestinal morphology did not change during the course of the experiment provide the first evidence of tGLP-1 as a hormonal signal regulating fructose transport.