Enzymes and Coenzymes Commons^™

A Survey Of Oxidative Paracatalytic Reactions Catalyzed By Enzymes That Generate Carbanionic Intermediates: Implications For Ros Production, Cancer Etiology, And Neurodegenerative Diseases, Victoria Bunik, John Schloss, John T. Pinto, Natalia Dudareva, Arthur J L Cooper

NYMC Faculty Publications

Enzymes that generate carbanionic intermediates often catalyze paracatalytic reactions with O2 and other electrophiles not considered “normal” reactants. For example, pyridoxal 5′-phosphate (PLP)—containing pig kidney dopa decarboxylase oxidizes dopamine with molecular O2 to 3,4-dihydroxyphenylacetaldehyde at about 1% of the rate at which it catalyzes nonoxidative dopa decarboxylation. The mutant Y332F enzyme, however, catalyzes stoichiometric conversion of dopa to 3,4-dihydroxyphenylacetaldehyde, suggesting that even minor structural changes may alter or initiate paracatalytic reactions catalyzed by certain enzymes. Carbanions generated by several thiamine diphosphate (ThDP)—dependent enzymes react with different electrophiles, transforming some xenobiotics and endogenous compounds into potentially biologically hazardous products. The detrimental …

Pharmacological Chaperoning In Fabry Disease, Jerome Rogich

Masters Theses 1911 - February 2014

Fabry Disease is an X-­‐linked lysosomal storage disorder characterized by a variety of symptoms including hypohydrosis, seizures, cardiac abnormalities, skin lesions, and chronic pain. These symptoms stem from a lack of functional endogenous α-­‐ Galactosidase A (α-­GAL), which leads to an accrual of its natural substrate. The severity of the disease symptoms can be directly correlated with the amount of residual enzyme activity. It has been shown that an imino sugar, 1-deoxygalactonojirimycin (DGJ), can increase enzymatic activity and clear excess substrate. This pH-­‐dependent chaperoning phenomenon is believed to arise from the presence of aspartic acid 170 in the active site. …

Synthesis, Biochemical And Molecular Modelling Studies Of Antiproliferative Azetidinones Causing Microtubule Disruption And Mitotic Catastrophe, Niamh O'Boyle, Miriam Carr, Lisa M. Greene, Niall O. Keely, Andrew Js Knox, Thomas Mccabe, David G. Lloyd, Daniela M. Zisterer, Mary J. Meegan

Articles

The structure-activity relationships of antiproliferative β-lactams, focusing on modifications at the 4-position of the β-lactam ring, is described. Synthesis of this series of compounds was achieved utilizing the Staudinger and Reformatsky reactions. The antiproliferative activity was assessed in MCF-7 cells, where the 4-(4-ethoxy)phenyl substituted compound 26 displayed the most potent activity with an IC₅₀ value of 0.22 μM. The mechanism of action was demonstrated to be by inhibition of tubulin. Cell exposure to combretastatin A-4 and 26 led to arrest of MCF-7 cells in the G2/M phase of the cell cycle and induction of apoptosis. Additionally, mitotic catastrophe for …

Substituted Coumarin Derivatives: Synthesis And Evaluation Of Antiproliferative And Src Kinase Inhibitory Activities, Abha Kathuria, Sarah Jalal, Rakesh Tiwari, Amir Nasrolahi Shirazi, Shilpi Gupta, Shiv Kumar, Keykavous Parang, Sunil K. Sharma

Pharmacy Faculty Articles and Research

Six classes of coumarin derivatives (i.e. 3-alkyl-4-methylcoumarins, pyranocoumarins, coumarin carboxamides, quaternary ammonium coumarins, 7-aminocoumarins, and 4-aminocoumarins) were synthesized and evaluated for inhibition of cell proliferation of colon adenocarcinoma (HT-29), breast carcinoma (MDA-MB-468 or MCF-7), and human ovarian adenocarcinoma (SK-OV-3) cells. C-3-Alkyl substituted analogs of 4-methylcoumarins and pyranocoumarins, 5 and 6, inhibited the cell proliferation of MDA-MB-468 and SK-OV-3 cells by 53-74%, while 3-decyl substituted pyranocoumarin 10 and triethyl substituted quaternary ammonium coumarin derivative 29 inhibited the cell proliferation of HT-29 and SK-OV-3 cells by 63-72% at a concentration of 50 μM. Among all the compounds studied, C-3 decyl substituted quaternary …

Determination Of Important Ligand Sites For The Interaction With Aminoglycoside Acetyltransferase(3)-Iiib By Nmr, Katherine Jane Woodruff

Chancellor’s Honors Program Projects

No abstract provided.

Mechanisms Of Oxidant Generation By Catalase, Diane E. Heck, Michael Shakarjian, Hong-Duck Kim, Jeffrey Laskin, Anna M. Vetrano

NYMC Faculty Publications

The enzyme catalase converts solar radiation into reactive oxidant species (ROS). In this study, we report that several bacterial catalases (hydroperoxidases, HP), including Escherichia coli HP-I and HP-II also generate reactive oxidants in response to ultraviolet B light (UVB). HP-I and HP-II are identical except for the presence of NADPH. We found that only one of the catalases, HPI, produces oxidants in response to UVB light, indicating a potential role for the nucleotide in ROS production. This prompts us to speculate that NADPH may act as a cofactor regulating ROS generation by mammalian catalases. Structural analysis of the NADPH domains …

Interconversion Of The Specificities Of Human Lysosomal Enzymes, Ivan B. Tomasic

Masters Theses 1911 - February 2014

Fabry disease (FD) is an X-linked recessive lysosomal storage disorder (LSD) known to affect approximately 1 in every 40,000 males, and a smaller number of females. FD results from a deficiency of functional α-galactosidase (α-GAL), which leads to the accumulation of terminally α-galactosylated substrates in the lysosome. The predominant treatment is Enzyme Replacement Therapy (ERT), requiring the regular infusion of recombinant human α-GAL. More than half of individuals receiving ERT experience a range of adverse infusion reactions, and it has been reported that as many as 88% of patients receiving ERT develop neutralizing IgG antibodies against the drug.

In aim …

Pompe’S Disease And The Effects Of Alpha-Glucosidase Deficiency, Aaron Richler

The Science Journal of the Lander College of Arts and Sciences

The following is an excerpt from the introduction of this article: The energy that the body needs in order to function is obtained from carbohydrates that we get through our diet. These carbohydrates are monosacharides, disaccharides and polysacharides. The polysaccharides and disaccharides are hydrolyzed to monosaccharide’s such glucose (which comprises roughly 80%) fructose and galactose. Most cells convert the fructose and galactose to glucose. The body can use the glucose or store it. If energy is needed, glucose can be oxidized through the many reactions of glycolysis which gives a net production of 2 ATP and 2 NADH from one …

Paraoxonase 1 Activity As A Predictor Of Cardiovascular Disease In Type 2 Diabetes, Rozaida @ Poh Yuen Ying

Rozaida @ Poh Yuen Ying

The role of paraoxonase 1 in cardiovascular disease complications in type 2 diabetes mellitus is not fully understood. We studied paraoxonase activity towards paraoxon in 188 non-diabetic and 140 diabetic subjects using general linear models and univariate analysis. Adjusting for age revealed a reduction in activity towards paraoxon was associated with a significant increase in risk (p=0.023) for cardiovascular disease complications in diabetic patients. Multivariate analysis of two plasma measures of paraoxonase activity using paraoxon and diazoxon also showed reduced paraoxonase activity towards paraoxon was associated with a significant increase in risk (p=0.045) for cardiovascular disease complications in diabetic patients. …