Carbohydrates Commons^™

Abnormal Trafficking And Processing Of Multiple Matrix Metalloproteinases Drive Cartilage Defects In Congenital Disorders Of Glycosylation, Chia-Lun Wu

All Dissertations

Congenital Disorders of Glycosylation (CDG) are rare metabolic diseases caused by defects in glycosylation. Despite identification of over 200 CDG types, the mechanisms linking glycosylation defects to diverse clinical phenotypes remain unclear. This dissertation uses zebrafish models of PMM2-CDG and STT3-CDG to redefine CDG pathogenesis, shifting from a simple glycan deficiency model to one involving disrupted cellular spatial organization.

We identify a protease-dependent pathway underlying craniofacial cartilage defects. Specifically, defective proteolytic processing of N-cadherin, a key adhesion molecule in chondrogenesis, is a central driver of pathology. We further uncover an unconventional trafficking mechanism in which ER stress and altered secretory …

Towards Developing Glut2 Specific Probes For Biochemical And Biomedical Applications, Abdelrahman Ismail

Dissertations, Master's Theses and Master's Reports

Facilitated Glucose transporters (GLUTs) are membrane proteins responsible for the uptake of simple sugars and other structurally similar metabolites in all mammalian cells. One of the hallmarks of cancer is dysfunctional sugar metabolism, known as the Warburg effect, and one of the manifestations of that effect is abnormal GLUT expression. There are 14 known GLUT proteins with different expression patterns in different tissues, and tumors tend to express certain GLUTs that are not present in surrounding healthy tissue. Therefore, selective targeting of GLUTs presents a potentially powerful tool for diagnostics and treatment of cancer and other diseases. This has been …

Reversible Degradation Of Peptidoglycan By Lytic Transglycosylases, Aaron Devereaux

Theses and Dissertations (Comprehensive)

Antimicrobial resistance continues to be a burden on the global healthcare system with an estimated cost of billions of dollars and millions of deaths each year. Recently, there has been little to no development on new antibiotics to treat bacterial infection, and any that are developed become resisted to within a few years. Both Gram-positive and Gram-negative bacteria contain a mesh-like layer called peptidoglycan (PG) that surrounds their cells providing strength, cell shape, and protection from their environments. This layer is a polymer of N-acetylmuramic acid (MurNAc) and N-acetylglucosamine (GlcNAc) connected via a b-1,4-glycosidic bond, with each strand being cross-linked …

Deciphering The N-Glycomic And Collagen Proteomic Molecular Signatures Towards Breast Cancer Control And Prevention, Denys Rujchanarong

MUSC Theses and Dissertations

Breast cancer is the most diagnosed cancer among women worldwide and the incidence rates are rising annually. The rates of metastatic breast cancer are projected to increase by 54.3% from 2015 to 2030. Breast stroma plays a significant role in breast cancer risk and progression yet remains poorly understood. In breast stroma, regulation of post-translational modifications (PMTs) is representative of the health state of the local microenvironment. Two abundant PTMs in the extracellular matrix include hydroxylation of prolines (HYP) and N-glycosylation in collagen and non-collagen proteins, respectively. Here, mass spectrometry imaging (MSI) was used to investigate the spatial N-glycomic and …

Structural And Inhibitory Studies On (I)Two Mycobacterium Tuberculosis Enzymes Essential For Capsular Glucan Biosynthesis And Mrna Degradation: (Ii) Hantann Virus L-Protein Endonuclease Domain, Hettiarachchige Thilina D. Jayasinghe

Theses & Dissertations

Mycobacterium tuberculosis (Mtb) is the pathogenic bacterium species that causes Tuberculosis (TB). Understanding the major biosynthetic pathways responsible for cell viability is essential in developing new drugs against Mtb. The first two projects will reflect our approach in identifying inhibitors against Mtb GlgE, Mtb GpsI, and characterization of protein inhibitor interactions using X-ray crystallography.

The enzyme GlgE plays an essential role in the α-glucan biosynthesis pathway in Mtb cells. These α-glucans are one of the major structural units in the Mtb capsule. GlgE catalyzes the elongation of α-glucan by transferring maltose from maltose-1-phosphate (M1P) to the non-reducing end …

Metabolic Foundations Of Exercise-Induced Cardiac Growth., Kyle Fulghum

Electronic Theses and Dissertations

Regular aerobic exercise promotes physiological cardiac growth, which is an adaptive response thought to enable the heart to meet higher physical demands. Cardiac growth involves coordination of catabolic and anabolic activities to support ATP generation, macromolecule biosynthesis, and myocyte hypertrophy. Although previous studies suggest that exercise-induced reductions in cardiac glycolysis are critical for physiological myocyte hypertrophy, it remains unclear how exercise influences the many interlinked pathways of metabolism that support adaptive remodeling of the heart. In this thesis project, we tested the general hypothesis that aerobic exercise promotes physiological cardiac growth by coordinating myocardial metabolism to promote glucose-supported anabolic pathway …

Identification And Characterization Of Butyrate-Producing Species In The Human Gut Microbiome, Grace Maline

Theses/Capstones/Creative Projects

Inflammatory Bowel Diseases (IBD) including ulcerative colitis, indeterminate colitis, and Crohn’s disease are increasingly common conditions that places a high physical and financial burden on individuals and global healthcare systems. Though many treatments exist for these conditions, their unpredictable nature and causation make them difficult to manage across the variety of IBD patients. Additionally, many of these treatments come with undesirable side effects or modes of delivery. Therefore, it is worthwhile to explore the use of Short Chain Fatty Acids (SCFAs) such as butyrate whose affects in the human gut include decreased inflammation and decreased risk of colorectal cancer. As …

Ketogenic Diet As A Preventative Measure Or Treatment Option For Osteoarthritistargeting Nfl Athletes As A High-Risk Group, Kelsi J. Smith

Selected Honors Theses

Osteoarthritis (OA) is a prevalent joint disease that results from the degradation of articular cartilage, leading to inflammation, pain, and eventual joint failure. At one time, it was thought that OA was only the result of the natural decline experienced in old age; however, various risk factors have now been identified that may contribute to an increased risk for developing OA. Risk factors may include joint loading, altered biomechanics, obesity, and joint injury, to which athletes are exposed at a high rate. NFL athletes are one group of athletes that have continued to show a high prevalence of arthritis in …

Reversible Glucan Phosphorylation In The Red Alga, Cyanidioschyzon Merolae, Corey Owen Brizzee

Theses and Dissertations--Molecular and Cellular Biochemistry

Starch and glycogen are an essential component for the majority of species and have been developed to maintain homeostasis in response to environmental changes. Water-soluble glycogen is an excellent source of quick, short-term energy in response to energy demands. In contrast, plants and algae have developed the macromolecule starch that is elegantly suitable for their dependence on external circumstances. Semi-crystalline starch is water-insoluble and inaccessible to most amylolytic enzymes, thus plants and algae have developed a coordinated system so that these enzymes can gain access to the denser starch energy cache. Starch-like semi-crystalline polysaccharides are also found in red algae, …

Development Of Hyaluronic Acid-Derived Macromolecular Agents For Multimodal Imaging Probes And Nanomedicine, William M. Payne

Theses & Dissertations

Cancer, one of the most challenging maladies facing modern medicine, is a complex family of diseases that requires a multifaceted treatment regime. In recent years, increased research effort has been placed on the development of nanoscale formulations as a potential method to improve therapeutic efficacy and offer better treatment. Both drug formulation and biomedical imaging has benefitted from the development of new, nanoscale agents. Hyaluronic Acid (HA), a naturally occurring glycosaminoglycan, is a promising platform for the development of new drug delivery systems. Furthermore, hyaluronic acid is the principal ligand for the cell surface receptor CD44, which is overexpressed on …

Characterizing Glycosaminoglycan And Glycosaminoglycan-Oligo Interactions With Cancer Stem Cells And Their Regulators, Rahaman Navaz Gangji

Theses and Dissertations

Tumor metastasis and recurrence account for more than 90% of cancer-associated deaths and are thought to occur due to a small subpopulation of neoplastic cells known as cancer stem cells (CSCs). Because CSCs are resistant to conventional chemotherapy, there is a critical need to develop CSC-targeting agents. Microenvironmental components, especially glycosaminoglycans (GAGs), play a key role in regulating CSC phenotype. GAGs such as heparan sulfate (HS) interact with hundreds of proteins and influence a variety of biological processes including tumor proliferation, angiogenesis, metastasis and stem cell biology.

Recently, the Desai and Patel laboratories have demonstrated that a hexasaccharide form of …

Arachidin 3 Modulation Of Lipid Metabolism In Rotavirus Infections, Stormey Wisdom

Electronic Theses and Dissertations

Rotavirus (RV) can cause severe and deadly gastroenteritis in young children, infants, and immunocompromised individuals. Previous studies have shown that arachidin 3 (A3) inhibits RV replication, and that RV replication is dependent on the presence of lipids. This study investigated the alteration of lipid metabolism by A3 in RV infected HT29.f8 cells. A decrease in the RV regulation of lipid biosynthesis genes was observed with the addition of A3 using qRT-PCR. Also, immunofluorescent and histochemical staining for neutral fats, a major component of cellular lipid droplets, revealed an increased accumulation with both RV and RV+A3 when compared to no virus …

Inhibition Of Cancer Stem Cells By Glycosaminoglycan Mimetics, Connor P. O'Hara

Theses and Dissertations

Connor O’Hara July 29, 2019

Inhibition of Cancer Stem Cells by Glycosaminoglycan Mimetics

In the United States cancer is the second leading cause of death, with colorectal cancer (CRC) being the third deadliest cancer and expected to cause over 51,000 fatalities in 2019 alone.¹ The current standard of care for CRC depends largely on the staging, location, and presence of metastasis.² As the tumor grows and invades nearby lymph tissue and blood vessels, CRC has the opportunity to invade not only nearby tissue but also metastasize into the liver and lung (most commonly).³ The 5-year survival rate …

Glycosaminoglycan Mimetics For The Treatment Of Cancer And Lung Inflammation, Shravan Morla

Theses and Dissertations

Glycosaminoglycans (GAGs) are linear polysaccharides whose disaccharide building blocks consist of an amino sugar and either uronic acid or galactose. They are expressed on virtually all mammalian cells, usually covalently attached to proteins, forming proteoglycans. GAGs are highly negatively charged due to an abundance of sulfate and carboxylic acid groups, and are structurally very diverse, with differences arising from chain length, the type of monomeric units, the linkages between each monomeric unit, the position of sulfate groups, and the degree of sulfation. GAGs are known to interact with a multitude of proteins, impacting diverse physiological and pathological processes. In addition, …

Glycosaminoglycan Lyases In The Preparation Of Oligosaccharides, Alhumaidi B. Alabbas

Theses and Dissertations

Glycosaminoglycans are heterogeneous polysaccharides that mediate important biological functions. There has been considerable interest in deciphering the precise GAG sequences that are responsible for protein interactions. In fact, several GAG oligosaccharides have been discovered to date as targeting proteins with higher level of specificity. Yet, it has been difficult to develop GAG oligosaccharides as drugs. One of the key reasons for this state of art is that GAG synthesis is extremely challenging and is highly structure-specific. Thus, much of the biology and pharmacology of GAG remains unknown and unexploited to date.

An alternative approach is to prepare GAG oligosaccharides using …

Roles Of Gabab, Muscarinic And Nicotinic Receptor Signaling In The Acquisition And Expression Of Fructose And Fat-Conditioned Flavor Preferences And Acquisition Of Quinine-Conditioned Flavor Avoidances In Rats, Francis M. Rotella

Dissertations, Theses, and Capstone Projects

In addition to increased intake of sweet solutions by mammals, learning, particularly classically-conditioned “Pavlovian-like” learning, also plays an important role. An orosensory conditioned flavor preference (CFP) can be elicited by pairing one novel flavor (conditioned stimulus, CS+) with a fructose solution and a second novel flavor (CS-) with a saccharin solution. Rats will prefer the CS+ flavor in a subsequent 2-bottle choice test with both flavors mixed in saccharin. Previous pharmacological analyses revealed that systemic administration of dopamine (DA) D1 and D2 as well as NMDA, but not opioid, receptor antagonists eliminated the acquisition (learning) of fructose-CFP. Further, expression of …

Synthesis And Evaluation Of A Novel Carbohydrate Template And Analogs Thereof For Potential Cns-Active Drugs, Emi Hanawa-Romero

Seton Hall University Dissertations and Theses (ETDs)

Central nervous system (CNS) disorders are becoming a major societal problem. Examples of well-known CNS disorders are: neurodegenerative disorders such as Parkinson's, Huntington's and Alzheimer’s diseases, epilepsy/seizures, addiction, bipolar disorder, catalepsy, meningitis, migraines, attention deficit/hyperactivity disorder (ADHD), and multiple sclerosis. CNS disorders can be caused by various factors and therefore can affect ages, genders and races of all.

The population of patients with CNS disorders is increasing and a significant percentage of patients have symptoms that are not controlled by existing treatments. In addition, since CNS disorders are chronic disorder, there is no cure and thus the patients have to …

Diversity Oriented Synthesis, Characterization And Anti-Cancer Activity Of Killer Peptide Nucleolipid Bioconjugates, Niki K. Rana

Seton Hall University Dissertations and Theses (ETDs)

The killer peptide sequence D-(KLAKLAK)₂ has been originally designed and developed as an antibacterial agent. Despite having excellent cytotoxicity towards bacteria, this sequence maintains low cell cytotoxity in malignant mammalian cell types such as cancer. The chemical basis for its selectivity has been attributed to its poly(cationic) amphiphilic nature, which facilitates cell permeability across the negatively charged bacterial membrane, but with limited permeability across the zwitterionic membrane of mammalian cells. The positively charged D-(KLAKLAK)₂ sequence has been found to accumulate on the surface of the mitochondria causing dissipation of the negatively charged mitochondrial membrane potential. This charge disruption …

Mouth Exposure To Carbohydrate Prior To Exercise Possibly Impairs The Efficacy Of Carbohydrate Mouth Rinsing During Exercise, Kevin Decker

Masters Theses, 2010-2019

Decker K. P., M. J. Saunders, N. D. Luden, C. J. Womack, and N. J. Hladick. Mouth Exposure to Carbohydrate Prior to Exercise Possibly Impairs the Efficacy of Carbohydrate Mouth Rinsing during Exercise. Purpose: Carbohydrate mouth-rinsing (CHO-MR) during intense endurance exercise has been associated with improved cycling performance, due to neurological influences. However, prior studies have reported the efficacy of CHO-MR is attenuated following a pre-exercise meal. To determine if this outcome is related to desensitization of CHO receptors (rather than metabolic effects following digestion), this study will investigate whether CHO-MR prior to exercise influences cycling performance when CHO-MR …

Engineering A Mutation In The Heparin Binding Pocket Of The Human Fibroblast Growth Factor, Roshni Patel

Chemistry & Biochemistry Undergraduate Honors Theses

Fibroblast growth factors (FGFs) are family of proteins that belong to a group of growth factors that are found in mammals and play an important role in angiogenesis, differentiation, organogenesis, and tissue repair. In summary, their main functionality is involved in cell division and proliferation. Because FGFs plays such a vital role in cell proliferation, they are mainly involved in the process of wound healing and injuries. FGF binds to its ligand, heparin—a heavily sulfated glycosaminoglycan. The binding of heparin to FGF occurs through electrostatic interactions, specifically between the negatively charged sulfate groups on heparin and positively charged residues such …

Probing Allosteric, Partial Inhibition Of Thrombin Using Novel Anticoagulants, Stephen S. Verespy Iii

Theses and Dissertations

Thrombin is the key protease that regulates hemostasis; the delicate balance between procoagulation and anticoagulation of blood. In clotting disorders, like deep vein thrombosis or pulmonary embolism, procoagulation is up-regulated, but propagation of clotting can be inhibited with drugs targeting the proteases involved, like thrombin. Such drugs however, have serious side effects (e.g., excessive bleeding) and some require monitoring during the course of treatment. The reason for these side effects is the mechanism by which the drugs’ act. The two major mechanisms are direct orthosteric and indirect allosteric inhibition, which will completely abolish the protease’s activity. Herein we sought an …

Chemoenzymatic Studies To Enhance The Chemical Space Of Natural Products, Jhong-Min Chen

Theses and Dissertations--Pharmacy

Natural products provide some of the most potent anticancer agents and offer a template for new drug design or improvement with the advantage of an enormous chemical space. The overall goal of this thesis research is to enhance the chemical space of two natural products in order to generate novel drugs with better in vivo bioactivities than the original natural products.

Polycarcin V (PV) is a gilvocarcin-type antitumor agent with similar structure and comparable bioactivity with the principle compound of this group, gilvocarcin V (GV). Modest modifications of the polyketide-derived tetracyclic core of GV had been accomplished, but the most …

Polymer Interactions With Nucleic Acids Under Various Physiological Conditions, Matthew S. Obrzut

Williams Honors College, Honors Research Projects

The goal of this project is to improve our understanding of nucleic acid interactions with cationic polymers with the theory that the polymers could protect the nucleic acids from degradation caused by biological enzymes. We seek to understand what the limitations of the cationic polymers are which, in this case, is mainly polymer-DNA compatibility. This experiment utilized peptide-dextran hybrid polymers with differing functionalizations to condense anionic nucleic acids into nanometer-sized polyplexes. Techniques of dynamic light scattering and zeta-potential were utilized to determine the particle sizes and surface charges of polyplexes.

In this experiment, dextran with a molecular weight of 20 …

Signal Transduction In Bacterial Chemotaxis, Edward Heath Rowsell

Loma Linda University Electronic Theses, Dissertations & Projects

This study investigated the site of ATP utilization in the signal transduction pathway of bacterial chemotaxis and localized the point of convergence of a methylation-independent system of chemotaxis with the methylation-dependent system. The identity of the signal originating from the phosphotransferase system was investigated by substituting the fructose-inducible HPr-like protein FPr for HPr in transport and chemotaxis. In addition, a novel chemoattractant, glycerol, was identified for Salmonella typhimurium. Histidine-auxotrophic S. typhimurium strains ST23 (hisF) and ST171 (hisF cheB) were depleted for ATP. The times required for the bacteria to adapt to a step increase in serine, …

Effect Of Glucose Administration On Hamster Liver S9-Mediated Mutagenesis, Metabolism And Dna-Binding Of Benzo[A]Pyrene And Aflatoxin B1, Daniel C. Rubano

Loma Linda University Electronic Theses, Dissertations & Projects

Hamster liver S9 prepared from control animals and animals given 30% glucose in drinking water 48 h before time of sacrifice was used in studies of benzo[a]pyrene (BaP) and aflatoxin (AFB₁)-induced mutagenesis, metabolism of BaP and AFB₁, and metabolite binding to calf thymus DNA. BaP-induced mutagenesis in Salmonella typhimurium TA100 was reduced 38.5% while AFB₁-induced mutagenesis was increased 36% by S9 from glucose-treated hamsters. The reduction of [³H]BaP metabolite binding to calf thymus DNA in incubations with S9 from glucose-treated hamsters correlated with a decrease in unknown BaP metabolite-deoxyribonucleoside adducts isolated by …

Muscle Catabolism During A Protein Sparing Modified Fast As Measured By Urinary 3-Methylhistidine, Judith D. Nielsen

Loma Linda University Electronic Theses, Dissertations & Projects

The urinary excretion of 3-Methylhistidine was used as an index of muscle catabolism in four groups of obese persons receiving a Protein Sparing Modified Fast (PSMF). The composition of the supplements were as follows: Group I: 75 g protein, 25 g complex carbohydrate (starch) per day; Group II: 25 g protein, 75 g complex carbohydrate (starch) per day; Group III: 75 g protein, 25 g simple carbohydrate (glucose) per day; Group IV: 25 g protein, 75 g simple carbohydrate (glucose) per day. The PSMF lasted for seven days and a 24-hour urine sample was collected at the beginning of the …

The Duration Of The Effect Of Different Carbohydrates On Neutrophilic Phagocytosis, Judy L. Reeser

Loma Linda University Electronic Theses, Dissertations & Projects

In order to determine the duration of the effect of glucose, fructose, sucrose, honey, starch, and orange juice on neutrophilic phagocytosis, 10 subjects underwent a complete series of carbohydrate tolerance tests. Blood samples were drawn at specific time periods following ingestion of 100 grams of each carbohydrate. Blood was then analyzed for glucose and phagocytic index (the mean number of bacteria engulfed per leukocyte); a red blood cell and white blood cell count and differential white cell count were done also on about 1/2 of the samples. In addition, 7 other subjects participated in a fasting study in which no …

Some Aspects Of Carbohydrate Metabolism In The Cercariae Of Schistosoma Mansoni Sambon, 1907, A. Eugene Dunham Jr.

Loma Linda University Electronic Theses, Dissertations & Projects

Cercariac of Schistosoma mansoni were studied for glycogen utilization, uptake of glucose from solution, lactic acid production, and respiration.

Using the anthrone method of determination of carbohydrate, the amount of glycogen used by a single cercaria in 4 hours is determined as 43.2 x 10^-4 μg ± 6.6 x 10^-4 μg.

Glucose was not observed to have been used from solution under the conditions of the experiment, even in the presence of trehalose. The determinations were made by the Glucostat method.

After deproteinization and desugarization, aliquots of supernatant from cercarial suspensions were analyzed for lactic acid using p-phenylphenol …

A Review Of Drug Addiction And A Study Of Its Relation To Carbohydrate Metabolism, Eppie Chung Hartsuiker

Loma Linda University Electronic Theses, Dissertations & Projects

The specter of addiction eventually involves everyone of the community. It is a three-fold problem of socio-economic, psychological, and physiological factors. The least understood is the physiological or biochemical aspect of addiction.

It has been postulated that an upset in carbohydrate metabolism may be a biochemical cause of addiction. Several avenues were employed to investigate this possible cause of addiction.

1. A diet survey was conducted and revealed a greater consumption of refined carbohydrates, confections and alcoholic beverages in addicts.

2. Five-hour oral glucose tolerance tests were performed on 7 addicts and 12 non-addicts. These tests revealed that there were decreased glucose …

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