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Biochemistry

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Articles 1 - 30 of 66

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Glucose Metabolism Of Breast Cancer Sub-Clones That Preferentially Metastasize To The Lungs And Bone, Anna G. Skubiz May 2020

Glucose Metabolism Of Breast Cancer Sub-Clones That Preferentially Metastasize To The Lungs And Bone, Anna G. Skubiz

Honors Theses

Malignant breast cancers exhibit preferential metastasis to bone and lung (1). While changes in gene expression in lung-specific (LM) and bone-specific metastasis (BoM) lines derived from the MDA-MB-231 breast cancer line have been identified, few metabolic genes are differentially expressed; thus it is unknown if tissue-specific metabolic reprogramming occurs. Two hallmarks of cancer cells are an altered metabolic phenotype characterized by enhanced conversion of glucose to lactate in spite of adequate oxygen availability for complete mitochondrial oxidation of this substrate (referred to as aerobic glycolysis or the Warburg effect) and a greater dependence on glutamine. These changes in primary tumor ...


Xenobiotic Exposure Requires Mitochondrial Metabolism For Redox Homeostasis And Survival In Astrocytes, Jordan Rose Dec 2019

Xenobiotic Exposure Requires Mitochondrial Metabolism For Redox Homeostasis And Survival In Astrocytes, Jordan Rose

Theses and Dissertations in Biochemistry

Astrocytes are integral components of glutamatergic neurotransmission, providing essential metabolic processes for neuronal homeostasis and acting as the first line of defense against xenobiotics crossing the blood brain barrier. Arsenic is a xenobiotic with widespread natural and industrial prevalence, and has been linked to impaired neurodevelopment and neuronal death. Given the integrated metabolic nature of astrocytes and neurons, we sought to explore how arsenic impacts astrocyte metabolism in order to better understand the mechanisms of xenobiotic toxicity in the mammalian brain.

We demonstrate that astrocyte viability depends upon de novoglutathione (GSH) synthesis during arsenic exposure, and sub-lethal arsenic exposure ...


Two Human Mitochondrial Pyruvate Carrier Mutations Reveal Distinct Mechanisms Of Molecular Pathogenesis, Lalita Oonthonpan Aug 2019

Two Human Mitochondrial Pyruvate Carrier Mutations Reveal Distinct Mechanisms Of Molecular Pathogenesis, Lalita Oonthonpan

Theses and Dissertations

The Mitochondrial Pyruvate Carrier (MPC) occupies a central metabolic node by transporting cytosolic pyruvate into the mitochondrial matrix, thereby linking glycolysis with mitochondrial metabolism. Two reported human MPC1 mutations cause developmental abnormalities, neurological problems, metabolic deficits, and for one patient, early death. We aimed to understand biochemical mechanisms by which the human patient c.C289T and c.T236A MPC1 alleles disrupt MPC function. MPC1 c.C289T encodes two protein variants, a mis-spliced, truncation mutant (A58G) and full-length point mutant (R97W). MPC1 c.T236A encodes a full-length point mutant (L79H). Using human patient fibroblasts and complementation of CRISPR-deleted, MPC1 null mouse ...


The Effects Of Inulin And Galactooligosaccharides On The Production Of Reuterin By Lactobacillus Reuteri, Micah Dwight Forshee Dec 2018

The Effects Of Inulin And Galactooligosaccharides On The Production Of Reuterin By Lactobacillus Reuteri, Micah Dwight Forshee

ELAIA

The microbiome is a dynamic community that can positively and negatively influence host health. Lactobacillus reuteri is a probiotic that has received much attention for its ability to inhibit pathogens such as Salmonella typhimurium, Escherichia coli, and Clostridium difficile. It does so by its unique ability to metabolize glycerol into the antimicrobial compound 3-HPA, which is commonly referred to as reuterin. The ability to secrete reuterin is dependent not only on glycerol availability but also the concentration of glucose. In fact, there appears to be a “goldilocks” ratio between glucose and glycerol as either too much or too little glucose ...


Regulation Of Plasma Triglycerides By Angptl4 And Gpihbp1, Emily Malcolm Cushing Aug 2018

Regulation Of Plasma Triglycerides By Angptl4 And Gpihbp1, Emily Malcolm Cushing

Theses and Dissertations

The absorption, packaging, and delivery of fat to appropriate peripheral tissues is essential for maintaining metabolic homeostasis, and defects or dysregulation of these processes can contribute to metabolic disorders such as diabetes, obesity, and hyperlipidemia. In the intestine, dietary fat is packaged into triglyceride-rich lipoprotein particles and delivered to peripheral tissues through the circulatory system.

Lipolysis of lipoprotein triglycerides requires the enzyme lipoprotein lipase (LPL) and takes place on the luminal surface of capillary endothelial cells. Lipolysis by LPL is regulated in part by two proteins, GPIHBP1 and ANGPTL4. GPIHBP1, a GPI-anchored protein of capillary endothelial cells, is responsible for ...


The Effects Of Inulin And Galactooligosaccharides On The Production Of Reuterin By Lactobacillus Reuteri, Micah Forshee Apr 2018

The Effects Of Inulin And Galactooligosaccharides On The Production Of Reuterin By Lactobacillus Reuteri, Micah Forshee

Scholar Week 2016 - present

The microbiome is a dynamic community that can positively and negatively influence host health. Lactobacillus reuteri is a probiotic that has received much attention for its ability to inhibit pathogens such as Salmonella Typhimurium, Escherichia coli, and Clostridium difficile. It does so by its unique ability to metabolize glycerol into the antimicrobial compound 3-HPA, which is commonly referred to as reuterin. The ability to secrete reuterin is dependent not only on glycerol availability but also the concentration of glucose. In fact, there appears to be a “goldilocks” ratio between glucose and glycerol as either too much or too little glucose ...


Regulation Of Liver Mitochondrial Metabolism During Hibernation By Post-Translational Modification, Katherine E. Mathers Dec 2017

Regulation Of Liver Mitochondrial Metabolism During Hibernation By Post-Translational Modification, Katherine E. Mathers

Electronic Thesis and Dissertation Repository

Hibernation, characterized by a seasonal reduction in metabolism and body temperature, allows animals to conserve energy when environmental conditions (e.g. temperature, food availability) are unfavourable. During hibernation, small mammals such as the 13-lined ground squirrel (Ictidomys tridecemlineatus) cycle between two distinct metabolic states: torpor, where metabolic rate is suppressed by >95% and body temperature falls to ~5 °C, and interbout euthermia (IBE), where metabolic rate and body temperature rapidly increase and are maintained at euthermic levels several hours. Suppression of metabolism during entrance into torpor is paralleled by rapid suppression of liver mitochondrial metabolism. In my thesis, I aimed ...


Mitochondrial Reactive Oxygen Species In Lipotoxic Hearts Induces Post-Translational Modifications Of Akap121, Drp1 And Opa1 That Promote Mitochondrial Fission, Kensuke Tsushima, Heiko Bugger, Adam R. Wende, Jamie Soto, Gregory A. Jenson, Austin R. Tor, Rose Mcglauflin, Helena C. Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X. Hu, Crystal L. Sloan, Renata O. Pereira, Vitor A. Lira, Kenneth W. Spitzer, Terry L. Sharp, Kooresh I. Shoghi, Genevieve C. Sparagna, Eva A. Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E. Schaffer, E. Dale Abel Nov 2017

Mitochondrial Reactive Oxygen Species In Lipotoxic Hearts Induces Post-Translational Modifications Of Akap121, Drp1 And Opa1 That Promote Mitochondrial Fission, Kensuke Tsushima, Heiko Bugger, Adam R. Wende, Jamie Soto, Gregory A. Jenson, Austin R. Tor, Rose Mcglauflin, Helena C. Kenny, Yuan Zhang, Rhonda Souvenir, Xiao X. Hu, Crystal L. Sloan, Renata O. Pereira, Vitor A. Lira, Kenneth W. Spitzer, Terry L. Sharp, Kooresh I. Shoghi, Genevieve C. Sparagna, Eva A. Rog-Zielinska, Peter Kohl, Oleh Khalimonchuk, Jean E. Schaffer, E. Dale Abel

Biochemistry -- Faculty Publications

Rationale: Cardiac lipotoxicity, characterized by increased uptake, oxidation and accumulation of lipid intermediates, contributes to cardiac dysfunction in obesity and diabetes. However, mechanisms linking lipid overload and mitochondrial dysfunction are incompletely understood.

Objective: To elucidate the mechanisms for mitochondrial adaptations to lipid overload in postnatal hearts in vivo.

Methods and Results: Using a transgenic mouse model of cardiac lipotoxicity overexpressing long-chain acyl-CoA synthetase 1 in cardiomyocytes, we show that modestly increased myocardial fatty acid uptake leads to mitochondrial structural remodeling with significant reduction in minimum diameter. This is associated with increased palmitoyl-carnitine oxidation and increased reactive oxygen species (ROS) generation ...


Critical Role For Arginase 2 In Obesity-Associated Pancreatic Cancer, Tamara Zaytouni, Pei-Yun Tsai, Daniel S. Hitchcock, Cory D. Dubois, Elizaveta Freinkman, Lin Lin, Vicente Morales-Oyarvide, Patrick J. Lenehan, Brian M. Wolpin, Mari Mino-Kenudson, Eduardo M. Torres, Nicholas Stylopoulos, Clary B. Clish, Nada Y. Kalaany Aug 2017

Critical Role For Arginase 2 In Obesity-Associated Pancreatic Cancer, Tamara Zaytouni, Pei-Yun Tsai, Daniel S. Hitchcock, Cory D. Dubois, Elizaveta Freinkman, Lin Lin, Vicente Morales-Oyarvide, Patrick J. Lenehan, Brian M. Wolpin, Mari Mino-Kenudson, Eduardo M. Torres, Nicholas Stylopoulos, Clary B. Clish, Nada Y. Kalaany

UMass Metabolic Network Publications

Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDA remain unknown. Here we show that obesity-driven PDA exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDA. In vivo infusion of (15)N-glutamine in obese mouse models of PDA demonstrates enhanced nitrogen flux into the urea cycle and infusion of ...


Another Route For Amino Acid Production?: Reverse Genetic Probing For A Functional Cytosolic Shikimate Pathway In Plants, Gabrielle C. Buck, Joseph Lynch, Natalia Dudareva Aug 2017

Another Route For Amino Acid Production?: Reverse Genetic Probing For A Functional Cytosolic Shikimate Pathway In Plants, Gabrielle C. Buck, Joseph Lynch, Natalia Dudareva

The Summer Undergraduate Research Fellowship (SURF) Symposium

The shikimate pathway is a metabolic pathway that produces the three aromatic amino acids—phenylalanine, tryptophan, and tyrosine—which are essential to human diets and necessary for many plant functions. Consequently, the shikimate pathway is commonly targeted for antibiotic and herbicide strategies as well as genetic engineering in several fields. This pathway is known to be localized in the plastids, or double membrane-bound organelles, of plant cells; however, there is enzymatic evidence of another shikimate pathway in the cell fluid, or cytosol. To determine whether a complete cytosolic shikimate pathway exists, we used a modified gene for the first enzyme ...


Exploring Cancer Metabolism Using Stable Isotope-Resolved Metabolomics (Sirm), Ronald C. Bruntz, Andrew N. Lane, Richard M. Higashi, Teresa W. -M. Fan Jun 2017

Exploring Cancer Metabolism Using Stable Isotope-Resolved Metabolomics (Sirm), Ronald C. Bruntz, Andrew N. Lane, Richard M. Higashi, Teresa W. -M. Fan

Center for Environmental and Systems Biochemistry Faculty Publications

Metabolic reprogramming is a hallmark of cancer. The changes in metabolism are adaptive to permit proliferation, survival, and eventually metastasis in a harsh environment. Stable isotope-resolved metabolomics (SIRM) is an approach that uses advanced approaches of NMR and mass spectrometry to analyze the fate of individual atoms from stable isotope-enriched precursors to products to deduce metabolic pathways and networks. The approach can be applied to a wide range of biological systems, including human subjects. This review focuses on the applications of SIRM to cancer metabolism and its use in understanding drug actions.


A Genetic Analysis Of Nuclear Functions Of The Lipin Protein In Drosophila Melanogaster, Xeniya Rudolf May 2017

A Genetic Analysis Of Nuclear Functions Of The Lipin Protein In Drosophila Melanogaster, Xeniya Rudolf

Theses and Dissertations

Lipins are a family of proteins that have critical functions in the control of fat storage and energy homeostasis. Biochemically, lipins have two functions. They provide an enzymatic activity (phosphatidate phosphatase or PAP activity) in the glycerol-3 phosphate pathway that leads to the production of storage fats (triacylglycerols). In addition, they play a role in the regulation of genes in the cell nucleus as transcriptional co-regulators. The PAP activity of lipins has been widely studied in a number of organisms. However, the transcriptional co-regulator function is not as well described in the literature. The transcriptional function of lipins depends on ...


Therapeutic Exploitation Of Metabolic Checkpoints In Cancer Cells, Deven S. Patel Feb 2017

Therapeutic Exploitation Of Metabolic Checkpoints In Cancer Cells, Deven S. Patel

All Dissertations, Theses, and Capstone Projects

During the G1 phase of the cell cycle, normal cells respond to growth factors and nutrients prior to entering S-phase to replicate its genome. We previously reported that the growth factor-mediated restriction point is distinguishable from a series of late G1 metabolic checkpoints mediated by essential amino acids (EAAs), the conditionally essential amino acid glutamine (Gln), and mTOR – the mammalian target of rapamycin. Mutations in genes encoding proteins that regulate G1 cell cycle progression are observed in virtually all cancers. We observed that cancer cells with K-Ras mutations bypass the late G1 Gln checkpoint when deprived of Gln and instead ...


Lipid Sensing By Mammalian Target Of Rapamycin, Deepak Menon Feb 2017

Lipid Sensing By Mammalian Target Of Rapamycin, Deepak Menon

All Dissertations, Theses, and Capstone Projects

Mammalian target of Rapamycin (mTOR) is a protein kinase that integrates nutrient and growth factor signals to promote cellular growth and proliferation. mTOR exists in two complexes - mTORC1 and mTORC2 that are distinguished by their binding partners and signaling inputs. mTORC1 is responsive to growth factors, amino acids and glucose and is associated with Raptor; whereas, mTORC2 is responsive primarily to growth factors and is associated with Rictor. Raptor and Rictor confer substrate specificity to mTORC1 and mTORC2 respectively. Phosphatidic acid (PA), a lipid second messenger and a central metabolite for membrane phospholipid biosynthesis, is required for the stability and ...


Functions Of Maize Genes Encoding Pyruvate Orthophosphate Dikinase In Developing Maize Endosperm And Their Enzymatic Properties, Ryan R. Lappe Jan 2017

Functions Of Maize Genes Encoding Pyruvate Orthophosphate Dikinase In Developing Maize Endosperm And Their Enzymatic Properties, Ryan R. Lappe

Graduate Theses and Dissertations

The research described herein, focuses on investigating the role of pyruvate phosphate dikinase (PPDK) and factors influencing its activity in maize starchy endosperm (SE) tissue. PPDK reversibly converts phosphoenolpyruvate (PEP), pyrophosphate (PPi), and AMP, to pyruvate, phosphate (Pi), and ATP. PPDK is found in microorganisms and plant tissues with diverse functions. PPDK is abundant in maize SE during grain fill, but little is known about its role. Hypotheses were tested using transposon-insertion alleles affecting individual genes and by eliminating all PPDK expression using RNAi. PPDK's C4 metabolism function in mesophyll was proven to be essential in maize. RNAi transgenes ...


Cancer Metabolism: Fueling More Than Just Growth, Namgyu Lee, Dohoon Kim Dec 2016

Cancer Metabolism: Fueling More Than Just Growth, Namgyu Lee, Dohoon Kim

UMass Metabolic Network Publications

The early landmark discoveries in cancer metabolism research have uncovered metabolic processes that support rapid proliferation, such as aerobic glycolysis (Warburg effect), glutaminolysis, and increased nucleotide biosynthesis. However, there are limitations to the effectiveness of specifically targeting the metabolic processes which support rapid proliferation. First, as other normal proliferative tissues also share similar metabolic features, they may also be affected by such treatments. Secondly, targeting proliferative metabolism may only target the highly proliferating "bulk tumor" cells and not the slower-growing, clinically relevant cancer stem cell subpopulations which may be required for an effective cure. An emerging body of research indicates ...


The Biochemistry Of Cellobiose Metabolism In Sinorhizobium Meliloti, Myhanh T. Chu Jan 2016

The Biochemistry Of Cellobiose Metabolism In Sinorhizobium Meliloti, Myhanh T. Chu

Undergraduate Honors Theses

Sinorhizobium meliloti is a root-nodulating soil bacterium that is agriculturally important due to its ability to synthesize NH3 from N2 through the process of nitrogen fixation.1 To effectively harness S. meliloti's nitrogen-fixing ability, rhizobial metabolism of carbon sources found in the soil must be understood. Understanding how S. meliloti metabolizes cellobiose is important because cellobiose is a degradation product of the cellulose found in plant walls and cellulose is found in high concentrations in the soil.2,3 Growth on cellobiose was completely eliminated in constructed double mutant strains lacking a β-glucosidase and another unidentified gene ...


Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd Dec 2015

Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Normal Glycolytic Enzyme Activity is Critical for Hypoxia Inducible Factor-1α Activity and Provides Novel Targets for Inhibiting Tumor Growth

By Geoffrey Grandjean

Advisory Professor: Garth Powis, D. Phil

Unique to proliferating cancer cells is the observation that their increased need for energy is provided by a high rate of glycolysis followed by lactic acid fermentation in a process known as the Warburg Effect, a process many times less efficient than oxidative phosphorylation employed by normal cells to satisfy a similar energy demand [1]. This high rate of glycolysis occurs regardless of the concentration of oxygen in the cell and is ...


Allosteric Inhibition Of A Stem Cell Rna-Binding Protein By An Intermediary Metabolite, Carina Clingman, Laura Deveau, Samantha Hay, Ryan Genga, Shivender Shandilya, Francesca Massi, Sean Ryder Sep 2015

Allosteric Inhibition Of A Stem Cell Rna-Binding Protein By An Intermediary Metabolite, Carina Clingman, Laura Deveau, Samantha Hay, Ryan Genga, Shivender Shandilya, Francesca Massi, Sean Ryder

Sean P. Ryder

Gene expression and metabolism are coupled at numerous levels. Cells must sense and respond to nutrients in their environment, and specialized cells must synthesize metabolic products required for their function. Pluripotent stem cells have the ability to differentiate into a wide variety of specialized cells. How metabolic state contributes to stem cell differentiation is not understood. In this study, we show that RNA-binding by the stem cell translation regulator Musashi-1 (MSI1) is allosterically inhibited by 18-22 carbon omega-9 monounsaturated fatty acids. The fatty acid binds to the N-terminal RNA Recognition Motif (RRM) and induces a conformational change that prevents RNA ...


Biological Significance Of Photoreceptor Photocycle Length: Vivid Photocycle Governs The Dynamic Vivid-White Collar Complex Pool Mediating Photo-Adaptation And Response To Changes In Light Intensity, Arko Dasgupta, Chen-Hui Chen, Changhwan Lee, Amy S. Gladfelter, Jay C. Dunlap, Jennifer J. Loros May 2015

Biological Significance Of Photoreceptor Photocycle Length: Vivid Photocycle Governs The Dynamic Vivid-White Collar Complex Pool Mediating Photo-Adaptation And Response To Changes In Light Intensity, Arko Dasgupta, Chen-Hui Chen, Changhwan Lee, Amy S. Gladfelter, Jay C. Dunlap, Jennifer J. Loros

Open Dartmouth: Peer-reviewed articles by Dartmouth faculty

Most organisms on earth sense light through the use of chromophore-bearing photoreceptive proteins with distinct and characteristic photocycle lengths, yet the biological significance of this adduct decay length is neither understood nor has been tested. In the filamentous fungus Neurospora crassa VIVID (VVD) is a critical player in the process of photoadaptation, the attenuation of light-induced responses and the ability to maintain photosensitivity in response to changing light intensities. Detailed in vitro analysis of the photochemistry of the blue light sensing, FAD binding, LOV domain of VVD has revealed residues around the site of photo-adduct formation that influence the stability ...


Liquid Chromatography-Mass Spectrometry Analysis Of Dysfunctional Mitochondrial Metabolism: Insights Into Rotenone Toxicity And Friedreichâ'S Ataxia, Andrew J. Worth Jan 2015

Liquid Chromatography-Mass Spectrometry Analysis Of Dysfunctional Mitochondrial Metabolism: Insights Into Rotenone Toxicity And Friedreichâ'S Ataxia, Andrew J. Worth

Publicly Accessible Penn Dissertations

Mitochondrial dysfunction plays a role in a wide range of diseases resulting in an enormous public health burden. The goal of this thesis is to identify metabolic pathways that are disrupted in response to mitochondrial insults. A large proportion of this work is based on the generation of stable isotope labelled metabolites to allow for the rigorous quantification of intracellular metabolites by liquid chromatography-mass spectrometry. Once developed, this methodology was employed in cell culture models initially to characterize an unidentified acyl-CoA thioester induced by propionate metabolism. This novel pathway was identified as the direct formation of 2-methyl-2-pentenoyl-CoA, and using isotopic ...


Allosteric Inhibition Of A Stem Cell Rna-Binding Protein By An Intermediary Metabolite, Carina C. Clingman, Laura M. Deveau, Samantha A. Hay, Ryan M. J. Genga, Shivender Shandilya, Francesca Massi, Sean P. Ryder Jun 2014

Allosteric Inhibition Of A Stem Cell Rna-Binding Protein By An Intermediary Metabolite, Carina C. Clingman, Laura M. Deveau, Samantha A. Hay, Ryan M. J. Genga, Shivender Shandilya, Francesca Massi, Sean P. Ryder

Open Access Articles

Gene expression and metabolism are coupled at numerous levels. Cells must sense and respond to nutrients in their environment, and specialized cells must synthesize metabolic products required for their function. Pluripotent stem cells have the ability to differentiate into a wide variety of specialized cells. How metabolic state contributes to stem cell differentiation is not understood. In this study, we show that RNA-binding by the stem cell translation regulator Musashi-1 (MSI1) is allosterically inhibited by 18-22 carbon omega-9 monounsaturated fatty acids. The fatty acid binds to the N-terminal RNA Recognition Motif (RRM) and induces a conformational change that prevents RNA ...


Diabetes And Obesity Induce Transcriptomic And Metabolomic Changes Enhancing Pancreatic Cancer Aggressiveness, Guermarie Velázquez Torres May 2014

Diabetes And Obesity Induce Transcriptomic And Metabolomic Changes Enhancing Pancreatic Cancer Aggressiveness, Guermarie Velázquez Torres

The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access)

Pancreatic cancer is one of the most aggressive types of cancer, with poor prognosis that lacks effective diagnostic markers and therapies. It is expected that in 2014 the incidence and the mortality of pancreatic cancer in the United States will be 46,420 and 39,590 respectively. Diabetes and obesity are modifiable risk factors associated with accelerated pancreatic carcinogenesis and tumor progression, but the biological mechanisms are not completely understood. The purpose of this study is to demonstrate direct evidence for the mechanisms mediating these epidemiologic phenomena. Our hypothesis is that obesity and diabetes mellitus type 2 (DM2) accelerate pancreatic ...


Lipid Dependence In Ras-Driven Tumors, Darin Salloum Feb 2014

Lipid Dependence In Ras-Driven Tumors, Darin Salloum

All Dissertations, Theses, and Capstone Projects

Over past decade, metabolic alterations in cancer cells have received a substantial amount of interest. It had been established that cancer cells undergo a significant amount of metabolic alterations, and some of these alterations are similar to those in normal highly proliferative cells. However, it is becoming more apparent that many of the metabolic alterations are specific to particular oncogenic signaling pathways. Although altered metabolic machinery makes cancer cells more efficient at promoting growth when nutrients are supplied at the sufficient amounts, the dependency of cancer cells on particular metabolic reprogramming deems cancer cells susceptible to disruptions within metabolic network ...


Metabolic Checkpoints In Cancer Cell Cycle, Mahesh Saqcena Feb 2014

Metabolic Checkpoints In Cancer Cell Cycle, Mahesh Saqcena

All Dissertations, Theses, and Capstone Projects

Growth factors (GFs) as well as nutrient sufficiency regulate cell division in metazoans. The vast majority of mutations that contribute to cancer are in genes that regulate progression through the G1 phase of the cell cycle. A key regulatory site in G1 is the growth factor-dependent Restriction Point (R), where cells get permissive signals to divide. In the absence of GF instructions, cells enter the quiescent G0 state. Despite fundamental differences between GF signaling and nutrient sensing, they both have been confusingly referred to as R and therefore by definition considered to be a singular event in G1. Autonomy from ...


Redox-Dependent Stability, Protonation, And Reactivity Of Cysteine-Bound Heme Proteins, Fangfang Zhong, George P. Lisi, Daniel P. Collins, John H. Dawson, Ekaterina V. Pletneva Jan 2014

Redox-Dependent Stability, Protonation, And Reactivity Of Cysteine-Bound Heme Proteins, Fangfang Zhong, George P. Lisi, Daniel P. Collins, John H. Dawson, Ekaterina V. Pletneva

Open Dartmouth: Peer-reviewed articles by Dartmouth faculty

Cysteine-bound hemes are key components of many enzymes and biological sensors. Protonation (deprotonation) of the Cys ligand often accompanies redox transformations of these centers. To characterize these phenomena, we have engineered a series of Thr78Cys/Lys79Gly/Met80X mutants of yeast cytochrome c (cyt c) in which Cys78 becomes one of the axial ligands to the heme. At neutral pH, the protonation state of the coordinated Cys differs for the ferric and ferrous heme species, with Cys binding as a thiolate and a thiol, respectively. Analysis of redox-dependent stability and alkaline transitions of these model proteins, as well as comparisons to ...


The Development And Applications Of Nmr Metabolomics Analysis Of Bacterial Metabolomes, Steven M. Halouska Dec 2013

The Development And Applications Of Nmr Metabolomics Analysis Of Bacterial Metabolomes, Steven M. Halouska

Student Research Projects, Dissertations, and Theses - Chemistry Department

Metabolomics is a relatively new field that involves the study of metabolic responses that are occurring within a biological system. Metabolite profiles of an organism, tissue extract, and biofluids are important indicators to determine the physiological state of a biological profile. Comparison of such profiles from different phenotypes can be used to identify specific metabolic changes leading to the understanding of metabolic pathways, disease progression, drug toxicity and efficacy, and cellular responses to different intracellular and extracellular conditions. Metabolomics investigations often use sophisticated analytical techniques such as NMR spectroscopy to provide an unbiased and comprehensive approach to evaluate metabolic perturbation ...


Bioengineered Lysozyme Reduces Bacterial Burden And Inflammation In A Murine Model Of Mucoid Pseudomonas Aeruginosa Lung Infection, Charlotte C. Teneback, Thomas C. Scanlon, Matthew J. Wargo, Jenna L. Bement, Karl E. Griswold, Laurie W. Leclair Aug 2013

Bioengineered Lysozyme Reduces Bacterial Burden And Inflammation In A Murine Model Of Mucoid Pseudomonas Aeruginosa Lung Infection, Charlotte C. Teneback, Thomas C. Scanlon, Matthew J. Wargo, Jenna L. Bement, Karl E. Griswold, Laurie W. Leclair

Open Dartmouth: Peer-reviewed articles by Dartmouth faculty

The spread of drug-resistant bacterial pathogens is a growing global concern and has prompted an effort to explore potential adjuvant and alternative therapies derived from nature's repertoire of bactericidal proteins and peptides. In humans, the airway surface liquid layer is a rich source of antibiotics, and lysozyme represents one of the most abundant and effective antimicrobial components of airway secretions. Human lysozyme is active against both Gram-positive and Gram-negative bacteria, ac


Cellular Metabolism And Its Effect On The Type Iii Secretion System Of Dickeya Dadantii 3937, William Cortrell Hutchins Aug 2013

Cellular Metabolism And Its Effect On The Type Iii Secretion System Of Dickeya Dadantii 3937, William Cortrell Hutchins

Theses and Dissertations

Nutrition, in both eukaryotes and prokaryotes, is vital to the life and well-being of the species. In organisms such as Escherichia coli, metabolism and its regulation have been well established, whereas in Dickeya dadantii 3937, the metabolic pathways and their effects on other processes have not been elucidated. Little is known is how carbon metabolism is able to regulate virulence and pathogenicity in this organism. In this work, we have investigated how the metabolic network contributes to positively and negatively regulating the pathogenicity of Dickeya dadantii 3937.

Chapter 1 provides an overview of the history and virulence processes in the ...


Role Of Retinoids In The Regulation Of Hepatic Glucose And Lipid Metabolism, Rui Li May 2013

Role Of Retinoids In The Regulation Of Hepatic Glucose And Lipid Metabolism, Rui Li

Doctoral Dissertations

The liver plays an important role in controlling glucose and lipid homeostasis. Metabolic abnormalities such as obesity and type 2 diabetes are often associated with profound changes in the expression of genes involved in hepatic glucose and lipid metabolism. Dietary nutrients provide us with macronutrients for energy and micronutrients for maintenance of general health. However, the effects of individual micronutrients on the development of metabolic diseases are unknown. Sterol regulatory element binding protein-1c (SREBP-1c) is the master regulator of fatty acid synthesis, and glucokinase (GK) is the key enzyme in glucose metabolism. Based on the preliminary results from our laboratory ...