Biochemistry Commons^™

Role Of Dyslipidemia On Lipid Metabolism In Maintenance Hemodialysis Patients, Eno Latifi

Wayne State University Dissertations

Maintenance hemodialysis (MHD) patients experience various abnormalities such as systemic inflammation (SI), oxidative stress (OS), and dyslipidemia (D). Defined as an imbalance of plasma lipids, lipoproteins, and lipid metabolism enzymes, D has been associated with a rise in morbidity and mortality within ESRD patients due to cardiovascular disease (CVD). However, the contribution of each of these parameters to D is poorly understood; moreover, the impact of the following parameters on dyslipidemia in different ethnicities is unknown. Hence, the objective of this study was to characterize D in a multi-ethnic cohort of ESRD patients. We hypothesized that the degree of dyslipidemia …

Understanding The Mechanism Of Oxidative Stress Generation By Oxidized Dopamine Metabolites: Implications In Parkinson's Disease, Nihar Mehta

Wayne State University Dissertations

Oxidation of dopamine to toxic metabolites is considered to be one of the prime factors involved in the death of dopaminergic neurons in Parkinson’s disease. Some dopamine oxidation products have the capability to redox cycle in the presence of molecular oxygen, further contributing to oxidative stress. Therefore, our aim here was to study the redox cycling of dopamine oxidized metabolites and elucidate the underlying mechanism by which they cause oxidative stress.

Redox reactions involve transfer of one or more electrons between two compounds

resulting in either oxidation or reduction. In redox cycling, a compound undergoes

alternate oxidation and reduction, transferring …

Structural Characterization And Therapeutic Utility Of The Proton-Coupled Folate Transporter, Michael Roy Wilson

Wayne State University Dissertations

Folate is a B9 vitamin essential to DNA synthesis. The proton-coupled folate transporter (PCFT) is a newly discovered proton/folate symporter with an acidic pH optimum and broad expression across a variety of solid tumor types, with limited expression in normal tissues. Several antifolate molecules have been developed as cancer therapeutics, although these classical antifolates display numerous off-target effects due to transport by the ubiquitous reduced folate carrier (RFC). In this dissertation, we determine the roles of multiple PCFT structure/function domains, and develop PCFT-specific antifolates to target solid tumors. We utilize substituted cysteine accessibility methods (SCAM) to identify a novel reentrant …

Understanding The Gender-Based Mechanism Of Mso In Als Mice: A Metabolic Characterization Of The Sod1-G93a Mouse Model, Monica Ann Bame

Wayne State University Dissertations

Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease characterized by motor neuron death and a corresponding loss of neuromuscular connections resulting in muscle atrophy. Patients become paralyzed shortly after symptom onset and typically die within one to five years of pulmonary complications. ALS is a relatively rare disease, with an overall incidence of approximately 2 in 100,000 people per year and a prevalence of about 5 in 100,000 people. It is typically associated with increasing age and has a slight male prevalence, with a male to female ratio of approximately 3:2. ALS is classified as either familial (the less …

Enzymology And Medicinal Chemistry Of N5-Carboxyaminoimidazole Ribonucleotide Synthetase : A Novel Antibacterial Target, Hanumantharao Paritala

Wayne State University Dissertations

N5-Carboxyaminoimidazole ribonucleotide synthetase (N5-CAIR synthetase), a key enzyme in microbial de novo purine biosynthesis, catalyzes the conversion of aminoimidazole ribonucleotide (AIR) to N5-CAIR. To date, this enzyme has been observed only in microorganisms, and thus, it represents an ideal target for antimicrobial drug development. Here we report structural and functional studies on the Aspergillus clavatus N5-CAIR synthetase and identification of inhibitors for the enzyme. In collaboration with Dr. Hazel Holden of the University of Wisconsin, the three-dimensional structure of Aspergillus clavatus N5-CAIR synthetase was solved in the presence of either Mg2ATP or MgADP and AIR. These structures, determined to 2.1 …