Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 14 of 14 for “"cytochrome P450 3A4"”.
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Global deconvolution of heterotropic cooperativity in cytochrome P450 3A4
Cytochrome P450 3A4 (CYP3A4) plays a central role in xenobiotic metabolism, and is of critical importance to both human health and the pharmaceutical industry. Its ability to interact with multiple molecules of the same substrate, or multiple substrates, leads to complex non-Michaelis kinetics, …
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Electrochemical dynamics of cytochrome P450-3A4 isoenzyme biosensor for protease inhibitor antiretroviral drug
… 2), with human recombinant heme thiolate, cytochrome P450 3A4 isoenzyme (CYP3A4), as biorecognition component. Secondly, each biosensor platform was evaluated by using an entirely different category of compound as model substrate, with the overall objective being the development of …
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Characterization of Monomeric Human Cytochrome P450 3A4 and Cytochrome P450 Reductase in Nanoscale Phospholipid Bilayer Discs
… cause the conformational heterogeneity of CYP3A4 in other solubilization systems have complicated the complete biophysical characterization in comparison to similar soluble bacterial counterparts. The use of a discrete soluble nanoscale phospholipid bilayer system with an incorporated CYP3A4 …
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Human Cytochrome P450 3A4 Over-Expressing IEC-18 and MDCK Cell Lines as an In-Vitro Model to Assess Gut Permeability and the Enzyme Metabolism
… of drug metabolism enzyme expression such as CYP3A4, which contributes to significant first-pass gut and liver metabolism for many drugs. Consequently, these cell lines are not sufficient to integrate metabolism when assessing drug absorption. Here, we tested MDCK and IEC-18 cells transiently …
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Multidimensional Solid-State NMR Studies of Membrane Proteins
… bilayer system, and Nanodisc-embedded human cytochrome P450 3A4. For DsbB, nearly complete 13C and 15N chemical shift assignment was achieved for the transmembrane region of the protein from 3D and 4D chemical shift correlation experiments. Nanodisc is a nanoscale lipid bilayer system that …
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Prediction of Metabolic Stability and Bioavailability with Bioisosteric Replacements
… issues caused by the metabolic enzyme, cytochrome P450 3A4, and transporter protein P-gylcoprotein are also investigated in this work, along with the potential synergistic relationship between the two systems. In silico classifiers to distinguish substrates against non-substrates of the …
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A THREE DIMENSIONAL MODEL OF HUMAN HEPATO-BILIARY ORGANOGENESIS
… to albumin and isoform switch of fetal cytochrome P450 3A7 to adult cytochrome P450 3A4. Functionally, the organoids displayed albumin and urea secretion along with phase 1 metabolism of diazepam and 7-ethoxy coumarin. The cholangiocytes formed bile duct structures by undergoing biliary …
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Ligand and Protein Dynamics of CYP3A4
Cytochrome P450 3A4 (CYP3A4) dominates drug metabolism in humans. Examples of promiscuity (binding and catalytic) and allosterism in CYP3A4 are ubiquitous but poorly understood. This work is dedicated to improving our understanding of the linkage between ligand binding and protein conformational …
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Intestinal absorption barriers as modelled by p-glycoprotein and cytochrome p450 a34 in caco2 cells
… D3 induces their expression of cytochrome P450 3A4 protein to the level that is equivalent to that from isolated human jejunal cells. Under the same treatment, doxorubiein-exposed (Type I) cells metabolise naidazolam poorly and less extensively compared to non-exposed cells, …
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Studies on the metabolic bioactivation of haloperidol (HP) and its tetrahydropyridine dehydration product
… demonstrated that human monoamine oxidase A and cytochrome P450 3A4 are capable of catalyzing the oxidation of HPTP and/or HP to the toxic HP pyridinium metabolite {4-(4-chlorophenyl)-1-[4- (4-fluorophenyl)-4-oxobutyl]pyridinium species (HPP⁺). Rodent liver and brain preparations also catalyze …
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The significance of OATP and CYP450 in statin-flavonoid interactions
… the possible significance of OATP transport, CYP450 metabolism and mevalonate synthesis” reviews what is currently know about how flavonoids may interact with statin hepatic transport and metabolism, identifies what flavonoids are inhibitors of these pathways, how this compares to known …
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Structural Dynamics and Reaction Reversibility of Specific vs. Promiscuous Detoxification Enzymes
… of two highly promiscuous detoxification enzymes cytochrome P450 3A4 (CYP3A4) and glutathione transferase A1-1 (GSTA1-1) with that of structurally related, substrate-specific counterparts CYP19A1 and GSTA4-4. Two aspects of enzyme behavior are considered: (I) structural dynamics in the absence and …
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Expanding the toolbox for precision medicine with silicon photonic microring resonators and microfluidic technologies
… rapid purification on the microfluidic scale. Cytochrome P450 3A4 was used to demonstrate the capabilities of the μNAP platform. Chapter 6 details the future directions for each of the described projects. The next steps for phosphoprotein detection with microring resonator arrays is to use the …