subject:(cytochrome P450)

1. Rhieu, Steve. Electrochemical, biochemical, structural studies of cytochrome P450 monooxygenases involved in metabolism of vitamin D.

Degree: PhD, Biomedical Engineering, 2011, Brown University

URL: https://repository.library.brown.edu/studio/item/bdr:11352/

► This dissertation examines two cytochrome P450 monooxygenases, namely CYP27B1 and CYP24A1, for their potential applications in biosensors and drug metabolism, respectively. First, the feasibility of… (more)

▼ This dissertation examines two cytochrome P450 monooxygenases, namely CYP27B1 and CYP24A1, for their potential applications in biosensors and drug metabolism, respectively. First, the feasibility of using CYP27B1 as a biocatalyst was explored in an attempt to develop an electrochemical biosensor for measuring vitamin D levels. Electrochemical properties of CYP27B1 were characterized using an edge-plane graphite electrode functionalized with synthetic surfactants to facilitate heterogeneous electron transfer. Cyclic voltammetry in a deoxygenated solution revealed excellent redox reversibility with a midpoint potential of -180 � 5 mV (vs. Ag/AgCl) and a rate constant of 3.5 � 0.6 s-1. However, no product was observed by electrode-driven catalysis despite the excellent electron transfer between CYP27B1 and the electrode. Both spectroscopic and biochemical analyses revealed the structural integrity of CYP27B1 is perturbed by the surfactants, thereby inducing a biologically inactive P420 isomer. These results contribute to the understanding of the apparently anomalous behavior of CYPs in bioelectronic devices. Second, the active form of vitamin D3, 1a,25-dihydroxyvitamin D3 (1) displays non-calcemic actions such as antiproliferative activities against certain types of cancer cells. However, the clinical use of 1 was limited by its side effect of hypercalcemia. To alleviate the calcemic side effects of 1, numerous vitamin D analogs were synthesized with an aim to block metabolic inactivation of 1 by CYP24A1 so that their therapeutic effects in target cells can be prolonged. To provide definitive evidence for the role of structural modifications incorporated into the analogs in their metabolic stability against CYP24A1, the metabolism of two synthetic analogs with 16-ene-23-yne modifications was examined using rat CYP24A1 in a reconstituted system. The metabolism study was accompanied by an in silico CYP24A1 crystal structure-calibrated docking analysis to gain an insight into the structural determinants of substrate recognition as a means to understand the metabolic profiles of given analogs. In addition, the metabolism of a less calcemic natural metabolite of 1, namely 1a,25-dihydroxy-3-epi-vitamin D3 (2), was examined. The end product of 2, 3-epi-calcitroic acid, was isolated and identified for the first time. Advisors/Committee Members: Palmore, G. Tayhas (Director), Reddy, G. Satyanarayana (Reader), Pacifici, Domenico (Reader), Brodsky, Alexander (Reader), MacDonald, John (Reader).

Subjects/Keywords: Cytochrome P450

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Rhieu, S. (2011). Electrochemical, biochemical, structural studies of cytochrome P450 monooxygenases involved in metabolism of vitamin D. (Doctoral Dissertation). Brown University. Retrieved from https://repository.library.brown.edu/studio/item/bdr:11352/

Chicago Manual of Style (16^th Edition):

Rhieu, Steve. “Electrochemical, biochemical, structural studies of cytochrome P450 monooxygenases involved in metabolism of vitamin D.” 2011. Doctoral Dissertation, Brown University. Accessed April 19, 2021. https://repository.library.brown.edu/studio/item/bdr:11352/.

MLA Handbook (7^th Edition):

Rhieu, Steve. “Electrochemical, biochemical, structural studies of cytochrome P450 monooxygenases involved in metabolism of vitamin D.” 2011. Web. 19 Apr 2021.

Vancouver:

Rhieu S. Electrochemical, biochemical, structural studies of cytochrome P450 monooxygenases involved in metabolism of vitamin D. [Internet] [Doctoral dissertation]. Brown University; 2011. [cited 2021 Apr 19]. Available from: https://repository.library.brown.edu/studio/item/bdr:11352/.

Council of Science Editors:

Rhieu S. Electrochemical, biochemical, structural studies of cytochrome P450 monooxygenases involved in metabolism of vitamin D. [Doctoral Dissertation]. Brown University; 2011. Available from: https://repository.library.brown.edu/studio/item/bdr:11352/

University of Manchester

2. Porro, Cristina Shino. Quantum mechanical/molecular mechanics studies of Cytochrome P450BM3.

Degree: PhD, 2011, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/quantum-mechanical – molecular-mechanics-studies-of-cytochrome-p450bm3(ad4255e7-b779-47a2-a2c5-8dbf6b603ca5).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538423

► Cytochrome P450 (P450) enzymes are found in all kingdoms of life, catalysing a wide range of biosynthetic and metabolic processes. They are, in fact, of… (more)

▼ Cytochrome P450 (P450) enzymes are found in all kingdoms of life, catalysing a wide range of biosynthetic and metabolic processes. They are, in fact, of particular interest in a variety of applications such as the design of agents for the inhibition of a particular P450 to combat pathogens or the engineering of enzymes to produce a particular activity. Bacterial P450BM3 is of particular interest as it is a self-sufficient multi-domain protein with high reaction rates and a primary structure and function similar to mammalian isoforms. It is an attractive enzyme to study due to its potential for engineering catalysts with fast reaction rates which selectively produce molecules of high value.In order to study this enzyme in detail and characterise intermediate species and reactions, the first step was to design a general hybrid quantum mechanical /molecular mechanics (QM/MM) computational method for their investigation. Two QM/MM approaches were developed and tested against existing experimental and theoretical data and were then applied to subsequent investigations.The dissociation of water from the water-bound resting state was scrutinised to determine the nature of the spin conversion that occurs during this transformation. A displacement of merely 0.5 Å from the starting state was found to trigger spin crossing, with no requirement for the presence of a substrate or large conformational changes in the enzyme.A detailed investigation of the sulfoxidation reaction was undertaken to establish the nature of the oxidant species. Both reactions involving Compound 0 (Cpd0) and Compound I (CpdI) confirmed a concerted pathway proceeding via a single-state reactivity mechanism. As the reaction involving Cpd0 was found to be unrealistically high, the reaction proceeds preferentially via the quartet state of CpdI. This QM/MM study revealed that the preferred spin-state and the transition state structure for sulfoxidation are influenced by the protein environment. P450cam and P450BM3 were found to have CpdI species with different Fe-S distances and spin density distributions, and the latter having a larger reaction barrier for sulfoxidation.A novel P450 species, the doubly-reduced pentacoordinated system, was characterised using gas-phase and QM/MM methods. It was discovered to have a heme radical coupled to two unpaired electrons on the iron centre, making it the only P450 species to have similar characteristics to CpdI. Calculated spectroscopic parameters may assist experimentalists in the identification of the elusive CpdI.

Subjects/Keywords: 572.7; Cytochrome P450; P450 BM3; QM/MM

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Porro, C. S. (2011). Quantum mechanical/molecular mechanics studies of Cytochrome P450BM3. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/quantum-mechanical – molecular-mechanics-studies-of-cytochrome-p450bm3(ad4255e7-b779-47a2-a2c5-8dbf6b603ca5).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538423

Chicago Manual of Style (16^th Edition):

Porro, Cristina Shino. “Quantum mechanical/molecular mechanics studies of Cytochrome P450BM3.” 2011. Doctoral Dissertation, University of Manchester. Accessed April 19, 2021. https://www.research.manchester.ac.uk/portal/en/theses/quantum-mechanical – molecular-mechanics-studies-of-cytochrome-p450bm3(ad4255e7-b779-47a2-a2c5-8dbf6b603ca5).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538423.

MLA Handbook (7^th Edition):

Porro, Cristina Shino. “Quantum mechanical/molecular mechanics studies of Cytochrome P450BM3.” 2011. Web. 19 Apr 2021.

Vancouver:

Porro CS. Quantum mechanical/molecular mechanics studies of Cytochrome P450BM3. [Internet] [Doctoral dissertation]. University of Manchester; 2011. [cited 2021 Apr 19]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/quantum-mechanical – molecular-mechanics-studies-of-cytochrome-p450bm3(ad4255e7-b779-47a2-a2c5-8dbf6b603ca5).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538423.

Council of Science Editors:

Porro CS. Quantum mechanical/molecular mechanics studies of Cytochrome P450BM3. [Doctoral Dissertation]. University of Manchester; 2011. Available from: https://www.research.manchester.ac.uk/portal/en/theses/quantum-mechanical – molecular-mechanics-studies-of-cytochrome-p450bm3(ad4255e7-b779-47a2-a2c5-8dbf6b603ca5).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538423

University of Utah

3. Moore, Chad Douglas. Dehydrogenation of Raloxifene by Cytochrome P450 3A4.

Degree: PhD, Pharmacology & Toxicology;, 2010, University of Utah

URL: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1401/rec/288

► Raloxifene was approved in 2007 by the FDA for the chemoprevention of breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high… (more)

▼ Raloxifene was approved in 2007 by the FDA for the chemoprevention of breast cancer in postmenopausal women with osteoporosis and in postmenopausal women at high risk for invasive breast cancer. The FDA's decision was based, in part, on a more favorable safety profile for raloxifene, as compared to the standard treatment of tamoxifen. However, recent studies have demonstrated the ability of raloxifene to form reactive intermediates and to act as a mechanism-based inactivator of cytochrome P450 3A4 (CYP3A4). The reactive raloxifene intermediate was theorized to be produced either through CYP3A4-mediated dehydrogenation to a di-quinone methide or through the more common oxygenation route to an arene oxide. However, the operative mechanism was never identified. The goal of this dissertation was to characterize the reactive intermediate formation from raloxifene, specifically the ability of CYP3A4 to catalyze the dehydrogenation of raloxifene to a di-quinone methide, using a combination of convent•i onal b•i oc«h emi•c ali and-i computati• onal techn•i ques. In the current woir k,1 8O incorporation studies were utilized to differentiate CYP3A4-mediated oxygenation versus dehydrogenation of raloxifene. These studies established that 3'-hydroxyraloxifene is produced exclusively via CYP3A4-mediated oxygenation with molecular O2. These studies also provided convincing evidence for the mechanism of CYP3A4-mediated dehydrogenation of raloxifene to a reactive di-quinone methide, and excluded the alternative arene oxide pathway. Furthermore, it was demonstrated that 7-hydroxyraloxifene, which was previously believed to be a typical 02-derived metabolite of CYP3A4, is in fact produced by a highly unusual hydrolysis pathway from a putative ester, formed by conjugation of a carboxylic acid moiety of CYP3A4 or another protein, with the di-quinone methide of raloxifene. The use of molecular modeling in conjunction with site-directed mutagenesis has extensively been used to study substrate orientation within the P450 active sites, and to identify potential residues involved in positioning and/or catalysis of these substrates. However, the effectiveness of these studies is highly dependent on the selection of the most accurate enzyme crystal structure. In the current work, we compared the ability of two commonly used CYP3A4 crystal structures, 1TQN and 1 WOE, to predict the sites of metabolism of two known CYP3A4 substrates, indapamide and raloxifene. Indapamide was used to evaluate the accuracy of the molecular model, while raloxifene was used to investigate the effects of adding partial charges to the P450 heme moiety to improve predictions of metabolic pathways by computation methods. The results demonstrated that while docking studies with both 1TQN and 1 WOE crystal structures could accurately predict the sites of indapamide metabolism, the interactions between the substrate and active site residues were different for each crystal structure. The addition of partial charges to the heme moiety of 1 WOE dramatically increased the…

Subjects/Keywords: Raloxifene; Dehydrogenation; Cytochrome P450 3A4

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Moore, C. D. (2010). Dehydrogenation of Raloxifene by Cytochrome P450 3A4. (Doctoral Dissertation). University of Utah. Retrieved from http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1401/rec/288

Chicago Manual of Style (16^th Edition):

Moore, Chad Douglas. “Dehydrogenation of Raloxifene by Cytochrome P450 3A4.” 2010. Doctoral Dissertation, University of Utah. Accessed April 19, 2021. http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1401/rec/288.

MLA Handbook (7^th Edition):

Moore, Chad Douglas. “Dehydrogenation of Raloxifene by Cytochrome P450 3A4.” 2010. Web. 19 Apr 2021.

Vancouver:

Moore CD. Dehydrogenation of Raloxifene by Cytochrome P450 3A4. [Internet] [Doctoral dissertation]. University of Utah; 2010. [cited 2021 Apr 19]. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1401/rec/288.

Council of Science Editors:

Moore CD. Dehydrogenation of Raloxifene by Cytochrome P450 3A4. [Doctoral Dissertation]. University of Utah; 2010. Available from: http://content.lib.utah.edu/cdm/singleitem/collection/etd2/id/1401/rec/288

Cornell University

4. Bardowell, Sabrina. The Role Of Vitamin E Hydroxylases In Vitamin E Metabolism And Status.

Degree: PhD, Nutrition, 2012, Cornell University

URL: http://hdl.handle.net/1813/31140

► Vitamin E is a group of compounds that are considered to be the most important lipophilic antioxidants, however there is still much unknown about the… (more)

▼ Vitamin E is a group of compounds that are considered to be the most important lipophilic antioxidants, however there is still much unknown about the biological actions of the various forms of vitamin E as well as the mechanisms that influence the concentration of vitamin E forms in tissues. Despite the common predominance of mainly [gamma]-tocopherol ([gamma]-TOH) in the diet, [alpha]-TOH is present in serum and tissues at levels 5-6 times that of [gamma]-TOH. The biological rational for this selectivity remains an enigma. The focus of this work was on the selective postabsorptive catabolism of non-[alpha]-TOH forms via the vitamin E-[omega]-oxidation pathway. Cytochrome P450 4F2 (CYP4F2) is the only known human enzyme shown to display TOH-[omega]-hydroxylase activity. In an effort to investigate the role of TOH-[omega]-hydroxylase activity in vitamin E metabolism and status, the functional murine ortholog of CYP4F2 was identified and the consequences of its deletion on vitamin E metabolism and status were determined. In vivo and in vitro studies revealed Cyp4f14 to be the major, but not the only, vitamin E-[omega]-hydroxylase in mice, and to have critical function in regulating body-wide vitamin E status. Disruption of Cyp4f14 expression resulted in hyper-accumulation of [gamma]-TOH in mice fed a soybean oil diet in which the major tocopherol was [gamma]-TOH. Supplementation of Cyp4f14-/- mice with high levels of [delta]- and [gamma]-TOH exacerbated the tissue enrichment of these forms of vitamin E. Through the use of metabolic cage studies, previously unappreciated mechanisms of vitamin E elimination were discovered, which served to counterbalance the metabolic deficit observed in Cyp4f14-/- mice. Fecal elimination of unmetabolized TOHs was determined to be a high capacity mechanism to be minimize diet induced accumulation of TOHs, especially at high dietary levels. Additionally, novel [omega]-1 and [omega]-2 vitamin E hydroxylase activities were discovered and were found to quantitatively important vitamin E elimination mechanisms. Cyp4f14-/- mice also revealed the existence of other hepatic TOH-[omega]-hydroxylase enzyme(s). Therefore genetically modified mice, in which no CYP activity was present in the liver, were utilized in order to eliminate all hepatic vitamin E metabolism. Metabolic cage studies revealed the presence of vitamin E hydroxylase activity in non-hepatic tissues. Mouse and human small intestine mucosa were found to have TOH-[omega]-hydoxylase activity, representing at least one site of extra-hepatic vitamin E metabolism. Lastly, the use of cell culture studies demonstrated that two polymorphisms in CYP4F2 functionally alter TOH-[omega]-hydroxylase activity, which may play a role in vitamin E status in humans. Overall, the current works lends new insights into the physiological role of the TOH-[omega]oxidation pathway as well as reveals novel mechanisms of vitamin E metabolism in both mice and humans, which play an important role in the regulation of vitamin E status. Advisors/Committee Members: Parker, Robert Stanley (chair), Cassano, Patricia Ann (committee member), Gu, Zhenglong (committee member), O'Brien, Kimberly O (committee member).

Subjects/Keywords: vitamin E; cytochrome P450; metabolism

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Bardowell, S. (2012). The Role Of Vitamin E Hydroxylases In Vitamin E Metabolism And Status. (Doctoral Dissertation). Cornell University. Retrieved from http://hdl.handle.net/1813/31140

Chicago Manual of Style (16^th Edition):

Bardowell, Sabrina. “The Role Of Vitamin E Hydroxylases In Vitamin E Metabolism And Status.” 2012. Doctoral Dissertation, Cornell University. Accessed April 19, 2021. http://hdl.handle.net/1813/31140.

MLA Handbook (7^th Edition):

Bardowell, Sabrina. “The Role Of Vitamin E Hydroxylases In Vitamin E Metabolism And Status.” 2012. Web. 19 Apr 2021.

Vancouver:

Bardowell S. The Role Of Vitamin E Hydroxylases In Vitamin E Metabolism And Status. [Internet] [Doctoral dissertation]. Cornell University; 2012. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/1813/31140.

Council of Science Editors:

Bardowell S. The Role Of Vitamin E Hydroxylases In Vitamin E Metabolism And Status. [Doctoral Dissertation]. Cornell University; 2012. Available from: http://hdl.handle.net/1813/31140

University of Guelph

5. Darch, Maryse. Role of the Cytochrome P450 2A5 in Bilirubin Metabolism and Clearance in C57BL/6 Mice.

Degree: MS, Department of Biomedical Sciences, 2016, University of Guelph

URL: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9464

► Cytochrome P450 2A5 (CYP2A5) is uniquely induced in response to liver injury, indicating that CYP2A5 may have a cytoprotective function. Others have proposed that CYP2A5… (more)

Subjects/Keywords: CYP2A5; Bilirubin; Cytochrome P450

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Darch, M. (2016). Role of the Cytochrome P450 2A5 in Bilirubin Metabolism and Clearance in C57BL/6 Mice. (Masters Thesis). University of Guelph. Retrieved from https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9464

Chicago Manual of Style (16^th Edition):

Darch, Maryse. “Role of the Cytochrome P450 2A5 in Bilirubin Metabolism and Clearance in C57BL/6 Mice.” 2016. Masters Thesis, University of Guelph. Accessed April 19, 2021. https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9464.

MLA Handbook (7^th Edition):

Darch, Maryse. “Role of the Cytochrome P450 2A5 in Bilirubin Metabolism and Clearance in C57BL/6 Mice.” 2016. Web. 19 Apr 2021.

Vancouver:

Darch M. Role of the Cytochrome P450 2A5 in Bilirubin Metabolism and Clearance in C57BL/6 Mice. [Internet] [Masters thesis]. University of Guelph; 2016. [cited 2021 Apr 19]. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9464.

Council of Science Editors:

Darch M. Role of the Cytochrome P450 2A5 in Bilirubin Metabolism and Clearance in C57BL/6 Mice. [Masters Thesis]. University of Guelph; 2016. Available from: https://atrium.lib.uoguelph.ca/xmlui/handle/10214/9464

University of Manchester

6. Matthews, Sarah. Characterisation and Engineering of Alkene Producing P450 Peroxygenases for Bioenergy Applications.

Degree: 2017, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308754

► OleTJE (CYP152L1) is a P450 peroxygenase that was first isolated from Jeotgalicoccus sp. 8456 in 2011. OleTJE is primarily a fatty acid decarboxylase, converting mid-chain… (more)

▼ OleTJE (CYP152L1) is a P450 peroxygenase that was first isolated from Jeotgalicoccus sp. 8456 in 2011. OleTJE is primarily a fatty acid decarboxylase, converting mid-chain fatty acids (C10:0 to C22:0) to terminal alkenes, which are industrially useful petrochemicals. Terminal alkenes are hydrophobic with high energy density, and are compatible with existing transportation infrastructure. Thus OleTJE has attracted considerable interest due to potential applications for generating “drop-in” biofuels. As a P450 peroxygenase, OleTJE is able to utilise H2O2 as a sole oxygen and hydrogen donor. This is atypical of P450s, which usually require electron transfer from redox partners to perform substrate oxidation. Other P450 peroxygenases have previously been characterised, including fatty acid hydroxylases P450 Spα (CYP152B1) from Sphingomonas paucimobilis and P450 BSβ (CYP152A1) from Bacillus subtilis. In addition to decarboxylation, OleTJE also hydroxylates fatty acids, generating 2-OH and 3-OH fatty acids as minor products. P450 BSβ has also been reported to perform low levels of decarboxylation. However, OleTJE has superior decarboxylase activity, posing questions about the mechanism of OleTJE. This thesis describes initial structural and biochemical characterisation of OleTJE. These data highlighted three amino acid residues thought to be key for effective catalysis: His85, Phe79 and Arg245. We hypothesised that the active site His85 could act as a proton donor to thereactive ferryl-oxo species compound I, allowing homolytic scission of the substrate C-Cα bond to form the alkene product. Phe79 sandwiches His85 between the heme, and Arg245 co-ordinates the fatty acid carboxylate moiety. I performed mutagenesis studies to probe the roles of these residues, creating H85Q, F79A, F79W, F79Y, R245L and R245E OleTJE mutants, and characterised them by a combination of spectroscopic, analytical and structural methods. I also developed a novel system, where OleTJE was fused to alditol oxidase (AldO) from Streptomyces coelicolor, creating a fusion protein where addition of glycerol drives hydrogen peroxide production and the decarboxylation of fatty acids. Finally, studies showed that OleTJE is capable of performing secondary oxidation of hydroxylated products, which has expanded our knowledge of OleTJE’s catalytic repertoire. This thesis also describes the initial characterisation of the OleTJE orthologue P450 KR from Kocuria rhizophila, which is also a terminal alkene-forming fatty acid decarboxylase. The crystal structure of P450 KR revealed an unusual dimeric state, with structural interactions unprecedented for a P450 enzyme. These data thus provide characterisation of two P450 peroxygenases involved in the production of terminal alkenes and which are of great interest as tools for the development of alternative sources of advanced biofuels. Advisors/Committee Members: LEYS, DAVID D, RIGBY, STEPHEN SEJ, Munro, Andrew, Leys, David, Rigby, Stephen.

Subjects/Keywords: OleT; Cytochrome P450; Biofuels

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Matthews, S. (2017). Characterisation and Engineering of Alkene Producing P450 Peroxygenases for Bioenergy Applications. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308754

Chicago Manual of Style (16^th Edition):

Matthews, Sarah. “Characterisation and Engineering of Alkene Producing P450 Peroxygenases for Bioenergy Applications.” 2017. Doctoral Dissertation, University of Manchester. Accessed April 19, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308754.

MLA Handbook (7^th Edition):

Matthews, Sarah. “Characterisation and Engineering of Alkene Producing P450 Peroxygenases for Bioenergy Applications.” 2017. Web. 19 Apr 2021.

Vancouver:

Matthews S. Characterisation and Engineering of Alkene Producing P450 Peroxygenases for Bioenergy Applications. [Internet] [Doctoral dissertation]. University of Manchester; 2017. [cited 2021 Apr 19]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308754.

Council of Science Editors:

Matthews S. Characterisation and Engineering of Alkene Producing P450 Peroxygenases for Bioenergy Applications. [Doctoral Dissertation]. University of Manchester; 2017. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:308754

University of Texas – Austin

7. Sunnadeniya, Rasika Mayanthi. Identification and functional analysis of betalain pathway genes.

Degree: PhD, Plant Biology, 2014, University of Texas – Austin

URL: http://hdl.handle.net/2152/46526

► Betalains, comprised of red betacyanins and yellow betaxanthins, are found in the single order, Caryophyllales, where most other flowering plants produce anthocyanins. They are derived… (more)

▼ Betalains, comprised of red betacyanins and yellow betaxanthins, are found in the single order, Caryophyllales, where most other flowering plants produce anthocyanins. They are derived from tyrosine via three enzymatic steps: 1. tyrosine is converted to L-DOPA; 2. L-DOPA is converted to the yellow betalamic acid (BA) intermediate; and 3. L-DOPA is also converted to the cyclo-DOPA intermediate. BA spontaneously condenses with amines or amino acid, to make yellow betaxanthins, and with cyclo-DOPA to make red betacyanins. Before the work reported here, the only step for which a pigment ring biosynthetic gene had been cloned was DOPA 4, 5-dioxygenase (DODA) functioning to produce BA. The work described here identified a novel cytochrome P450, CYP76AD1, and showed that CYP76AD1 is absolutely required to produce red pigments in beets. Expression in yeast verifies that it converts L-DOPA to cyclo-DOPA. Transcriptome data was generated on white and red beet varieties by next generation sequencing. In an attempt to find gene(s) responsible for the tyrosine hydroxylation step, two new CYP450 genes, CYP76AD6 and CYP76AD5 were identified. Expression in yeast showed that CYP76AD6, CYP76AD5, and CYP76AD1 are responsible for tyrosine hydroxylation of the betalain biosynthetic pathway. However, unlike CYP76AD1, CYP76AD6 and CYP76AD5 show only very slight activity on L-DOPA to produce cyclo-DOPA and cannot complement yellow beet roots to red. This thesis also studied the functional differences of the two DODA homologs, DODA1, known to act in the betalain pathway, and DODA2, which is more similar to DODA-like proteins in anthocyanin producing non–Caryophyllales species. Expression in beets, Arabidopsis, and in yeast shows that BvDODA1 functions in the betalain pathway and BvDODA2 does not. The conserved amino acids in the two DODA homologs were identified and mutated proteins were expressed in yeast to test whether they are responsible for the functional differences of the two homologs. Identifying members of this pathway represents an important contribution toward understanding the evolutionary replacement of anthocyanins by betalains within a single order, and fills a lack of knowledge by identifying the genes functioning at the two uncharacterized steps in the synthesis of betalain ring structure. Advisors/Committee Members: Lloyd, Alan M. (advisor), Fischer, Janice A (committee member), Mehdy, Mona (committee member), Roux, Stanley J (committee member), Chen, Jeffrey Z (committee member).

Subjects/Keywords: Betalain; Cytochrome P450; Anthocyanins

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Sunnadeniya, R. M. (2014). Identification and functional analysis of betalain pathway genes. (Doctoral Dissertation). University of Texas – Austin. Retrieved from http://hdl.handle.net/2152/46526

Chicago Manual of Style (16^th Edition):

Sunnadeniya, Rasika Mayanthi. “Identification and functional analysis of betalain pathway genes.” 2014. Doctoral Dissertation, University of Texas – Austin. Accessed April 19, 2021. http://hdl.handle.net/2152/46526.

MLA Handbook (7^th Edition):

Sunnadeniya, Rasika Mayanthi. “Identification and functional analysis of betalain pathway genes.” 2014. Web. 19 Apr 2021.

Vancouver:

Sunnadeniya RM. Identification and functional analysis of betalain pathway genes. [Internet] [Doctoral dissertation]. University of Texas – Austin; 2014. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/2152/46526.

Council of Science Editors:

Sunnadeniya RM. Identification and functional analysis of betalain pathway genes. [Doctoral Dissertation]. University of Texas – Austin; 2014. Available from: http://hdl.handle.net/2152/46526

University of Illinois – Urbana-Champaign

8. Duggal, Ruchia. Mechanistic investigation of human cytochromes P450 involved in hormone biosynthesis.

Degree: PhD, Biochemistry, 2017, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/99474

► CYP17A1 and CYP19A1 are the key cytochromes P450 involved in steroidogenesis. Mutations causing hypo- or hyper-activation of both these enzymes results in diseased states, including… (more)

▼ CYP17A1 and CYP19A1 are the key cytochromes P450 involved in steroidogenesis. Mutations causing hypo- or hyper-activation of both these enzymes results in diseased states, including cancers. In addition to carrying out mono-oxygenation reactions, both CYP17A1 and CYP19A1 also catalyze carbon-carbon lyase reactions. There is significant interest in developing therapeutics capable of specifically targeting the CYP17A1 lyase reaction to target androgen synthesis without impacting glucocorticoid production, and understanding of CYP19A1 reaction mechanism could similarly help guide design of mechanism based inhibitors for certain breast cancers. To interrogate mechanistic aspects of both these enzymes, I used Nanodisc technology for reconstituting active forms of these proteins in functional complexes with their effector proteins in a native-like membrane environment. Cytochrome P450 17A1 (CYP17A1) is a multi-functional enzyme, catalyzing synthesis of glucocorticoid precursors by hydroxylation of pregnene nucleus, and androgen biosynthesis by a second C-C lyase step, at the expense of glucocorticoid production. It has been recently confirmed in our lab that when 17-hydroxy-pregnenolone is a substrate, CYP17A1 lyase reaction proceeds through a non-conventional hemiketal intermediate. However, it remains unknown if the alternate substrate, 17-hydroxy-progesterone (OH-PROG) is transformed to androstenedione via this novel mechanism, by the traditional compound I (Cpd I) mechanism, or by a combination of the two. To this end, I investigated kinetic solvent isotope effects on steady state turnover for lyase reaction on OH-PROG. Further, cryo-trapped peroxo-anion intermediate was spectroscopically followed as the samples were thermally annealed. Resonance Raman spectroscopy (rR) on the trapped intermediate was also performed. Our results strongly indicate that the CYP17A1 mediated OH-PROG lyase proceeds through a hemiketal intermediate. Cytochrome b5 (cyt b5) is a small heme-protein, known to enhance the rate of the CYP17A1 lyase reaction by ~5 fold, while having little effect on hydroxylation. Investigation with a redox inactive form of cyt b5 indicated that for lyase enhancement, cyt b5 critically requires a redox effector role. In order to investigate the electron transfer by cyt b5 to CYP17A1, I employed stopped flow spectroscopy and compared the CYP17A1 reduction rates by cyt b5 that by cytochrome P450 reductase (CPR). RR was also performed on CYP17A1—cyt b5 complex investigate any conformational perturbations. Taken together, our results suggest that cyt b5 critically requires a redox transfer role is essential to enhance lyase reaction, and it reduces CYP17A1 oxy-complex ~10fold faster than CPR. RR on oxyferrous CYP17A1—cyt b5 complex indicated subtle conformational changes in the active site, which were heavily dependent on the identity of the substrate. CYP19A1 produces estrogens in a three-step reaction, the first two being hydroxylation steps, while the third step comprises a lyase step. The hydroxylation… Advisors/Committee Members: Sligar, Stephen G (advisor), Sligar, Stephen G (Committee Chair), Gennis, Robert B (committee member), Tajkhorshid, Emad (committee member), Schuler, Mary A (committee member).

Subjects/Keywords: Cytochrome P450 17A1 (CYP17A1); Cytochrome b5; CYP19A1

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Duggal, R. (2017). Mechanistic investigation of human cytochromes P450 involved in hormone biosynthesis. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/99474

Chicago Manual of Style (16^th Edition):

Duggal, Ruchia. “Mechanistic investigation of human cytochromes P450 involved in hormone biosynthesis.” 2017. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 19, 2021. http://hdl.handle.net/2142/99474.

MLA Handbook (7^th Edition):

Duggal, Ruchia. “Mechanistic investigation of human cytochromes P450 involved in hormone biosynthesis.” 2017. Web. 19 Apr 2021.

Vancouver:

Duggal R. Mechanistic investigation of human cytochromes P450 involved in hormone biosynthesis. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2017. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/2142/99474.

Council of Science Editors:

Duggal R. Mechanistic investigation of human cytochromes P450 involved in hormone biosynthesis. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2017. Available from: http://hdl.handle.net/2142/99474

9. Quesnot, Nicolas. Évaluation de la génotoxicité des contaminants environnementaux, production de lignées bio-senseurs et mesure de l'activité enzymatique du cytochrome P450 2E1 dans les cellules d'hépatome humain HepaRG : Evaluation of genotoxicity of environmental contaminants,production of bio-sensor cell lines and measurment of CYP2E1 enzymatic activity.

Degree: Docteur es, Biologie et sciences de la santé, 2015, Rennes 1

URL: http://www.theses.fr/2015REN1B005

► L'exposition humaine aux contaminants environnementaux est inévitable du fait de leur présence dans l'eau, l'air et l'alimentation. La plupart d'entre eux sont reconnus comme étant… (more)

▼ L'exposition humaine aux contaminants environnementaux est inévitable du fait de leur présence dans l'eau, l'air et l'alimentation. La plupart d'entre eux sont reconnus comme étant mutagènes et/ou carcinogènes chez l'animal mais ils sont souvent seulement suspectés de l'être chez l'Homme. Le manque de connaissance vis-à-vis des substances chimiques a conduit l'UE à lancer le programme REACH avec l'objectif d'évaluer la toxicité d'environ 30 000 molécules. Cette évaluation nécessiterait l'utilisation de plus de 4 millions d'animaux et la pertinence controversée de ces modèles pourrait aboutir à des conclusions discutables. Les méthodes in vitro sont considérées comme une alternative potentielle à l'expérimentation animale. Néanmoins, le choix du modèle cellulaire et des conditions expérimentales restent à préciser. Les hépatocytes humains en culture primaire représentent le modèle le plus pertinent en toxicologie malgré de nombreuses contraintes (variabilité inter-individuelle, changements phénotypique précoces, obtention aléatoire). La lignée HepaRG constitue une alternative intéressante puisque ces cellules peuvent proliférer de manière illimitée et expriment les EMXs à des niveaux proches des hépatocytes humains. L'expression de ces enzymes restant stable pendant plusieurs semaines, ce modèle permet l'évaluation du risque lié à une exposition chronique aux contaminents environnementaux, essentielle en génotoxicité. Il reste cependant nécessaire de caractériser plus amplement cette lignée vis-à-vis des EMXs et de l'adapter aux tests de toxicologie actuels. Dans ces travaux, nous avons développé un test haut débit utilisant la quantification in situ des histones phosphorylées γH2AX avec l'objectif de pouvoir évaluer le risque génotoxique d'une exposition unique ou répétée aux contaminants environnementaux. Ce test a été validé avec succès par l'évaluation de la génotoxicité associée à une exposition de 1, 7 et 14 jours pour 10 polluants. Nous avons ensuite généré des lignées recombinantes biosenseurs, dérivées du modèle HepaRG et permettant d'identifier les xénobiotiques altérant l'expression transcriptionnelle des EMXs. Par transfection transitoire, nous avons dans un premier temps validé à l'aide d'inducteurs prototypiques et de nos 10 contaminants nos constructions contenant le gène rapporteur de la luciférase sous le contrôle des promoteurs de plusieurs EMXs. Ensuite, nous avons généré des lignées stables exprimant la GFP comme gène rapporteur et permettant une détection rapide des xénobiotiques capables d'induire l'expression des EMXs. Parmi les EMXs, le CYP2E1 joue un rôle important en santé humaine. En effet, cette enzyme induite dans certaines conditions physiopathologiques comme le diabète et l'obésité est responsable de l'activation de nombreux procarcinogènes et est à l'origine d'une production d'EROs. Les cellules HepaRG pourraient constituer un modèle pertinent pour l'étude du CYP2E1. Cependant, l'expression et l'activité de cette enzyme au sein de ce modèle nécessitent d'être mieux caractérisées en… Advisors/Committee Members: Loyer, Pascal (thesis director), Robin, Marie-Anne (thesis director).

Subjects/Keywords: Cytochrome P450; Cyp2e1; Génotoxicité; Chlorzoxazone; Cytochrome P450; Cyp2e1; Genotoxicity; Chlorzoxazone

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Quesnot, N. (2015). Évaluation de la génotoxicité des contaminants environnementaux, production de lignées bio-senseurs et mesure de l'activité enzymatique du cytochrome P450 2E1 dans les cellules d'hépatome humain HepaRG : Evaluation of genotoxicity of environmental contaminants,production of bio-sensor cell lines and measurment of CYP2E1 enzymatic activity. (Doctoral Dissertation). Rennes 1. Retrieved from http://www.theses.fr/2015REN1B005

Chicago Manual of Style (16^th Edition):

Quesnot, Nicolas. “Évaluation de la génotoxicité des contaminants environnementaux, production de lignées bio-senseurs et mesure de l'activité enzymatique du cytochrome P450 2E1 dans les cellules d'hépatome humain HepaRG : Evaluation of genotoxicity of environmental contaminants,production of bio-sensor cell lines and measurment of CYP2E1 enzymatic activity.” 2015. Doctoral Dissertation, Rennes 1. Accessed April 19, 2021. http://www.theses.fr/2015REN1B005.

MLA Handbook (7^th Edition):

Quesnot, Nicolas. “Évaluation de la génotoxicité des contaminants environnementaux, production de lignées bio-senseurs et mesure de l'activité enzymatique du cytochrome P450 2E1 dans les cellules d'hépatome humain HepaRG : Evaluation of genotoxicity of environmental contaminants,production of bio-sensor cell lines and measurment of CYP2E1 enzymatic activity.” 2015. Web. 19 Apr 2021.

Vancouver:

Quesnot N. Évaluation de la génotoxicité des contaminants environnementaux, production de lignées bio-senseurs et mesure de l'activité enzymatique du cytochrome P450 2E1 dans les cellules d'hépatome humain HepaRG : Evaluation of genotoxicity of environmental contaminants,production of bio-sensor cell lines and measurment of CYP2E1 enzymatic activity. [Internet] [Doctoral dissertation]. Rennes 1; 2015. [cited 2021 Apr 19]. Available from: http://www.theses.fr/2015REN1B005.

Council of Science Editors:

Quesnot N. Évaluation de la génotoxicité des contaminants environnementaux, production de lignées bio-senseurs et mesure de l'activité enzymatique du cytochrome P450 2E1 dans les cellules d'hépatome humain HepaRG : Evaluation of genotoxicity of environmental contaminants,production of bio-sensor cell lines and measurment of CYP2E1 enzymatic activity. [Doctoral Dissertation]. Rennes 1; 2015. Available from: http://www.theses.fr/2015REN1B005

University of Alberta

10. Tse, Mandy M.Y. The role of cytochrome P450 and the protective effect of EETs against isoproterenol-induced cellular hypertrophy in rat H9c2 cell line.

Degree: MS, Faculty of Pharmacy and Pharmaceutical Sciences, 2013, University of Alberta

URL: https://era.library.ualberta.ca/files/3t945r43f

► Cytochrome P450 (CYP) enzymes have been identified in the heart and their levels have been reported to be altered during cardiac hypertrophy and heart failure.… (more)

Subjects/Keywords: hypertrophy; H9c2 cell; cytochrome P450; EETs

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tse, M. M. Y. (2013). The role of cytochrome P450 and the protective effect of EETs against isoproterenol-induced cellular hypertrophy in rat H9c2 cell line. (Masters Thesis). University of Alberta. Retrieved from https://era.library.ualberta.ca/files/3t945r43f

Chicago Manual of Style (16^th Edition):

Tse, Mandy M Y. “The role of cytochrome P450 and the protective effect of EETs against isoproterenol-induced cellular hypertrophy in rat H9c2 cell line.” 2013. Masters Thesis, University of Alberta. Accessed April 19, 2021. https://era.library.ualberta.ca/files/3t945r43f.

MLA Handbook (7^th Edition):

Tse, Mandy M Y. “The role of cytochrome P450 and the protective effect of EETs against isoproterenol-induced cellular hypertrophy in rat H9c2 cell line.” 2013. Web. 19 Apr 2021.

Vancouver:

Tse MMY. The role of cytochrome P450 and the protective effect of EETs against isoproterenol-induced cellular hypertrophy in rat H9c2 cell line. [Internet] [Masters thesis]. University of Alberta; 2013. [cited 2021 Apr 19]. Available from: https://era.library.ualberta.ca/files/3t945r43f.

Council of Science Editors:

Tse MMY. The role of cytochrome P450 and the protective effect of EETs against isoproterenol-induced cellular hypertrophy in rat H9c2 cell line. [Masters Thesis]. University of Alberta; 2013. Available from: https://era.library.ualberta.ca/files/3t945r43f

11. Nisbar, Nur Dayana binti. Characterisation of orphan cytochrome P450s from Mycobacterium tuberculosis H37Rv.

Degree: 2018, University of Manchester

URL: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:313431

► Tuberculosis is a disease that kills more people every year than any other infectious disease and is caused by the human pathogen, Mycobacterium tuberculosis (Mtb).… (more)

▼ Tuberculosis is a disease that kills more people every year than any other infectious disease and is caused by the human pathogen, Mycobacterium tuberculosis (Mtb). This disease can be treated by a standard six month course of four antimicrobial drugs that have been in use since the 1960s. However, the rise of multi-drug resistant and extensively drug-resistant strains of TB has complicated the efforts to eradicate the disease. Therefore, there is a critical need for the development of new anti-TB drugs with a novel mechanism of action that can speed up treatment duration and help avoid resistance. The discovery of twenty genes encoding cytochrome P450 enzymes in the Mtb H37Rv genome sequence has pointed to the significance of these enzymes in the physiology and pathogenicity of this bacterium. Consequently, the characterisation of these Mtb P450 enzymes may define their physiological roles of which can be a novel anti-tubercular drug target. To date, the characterisations of selected Mtb P450 enzymes have highlighted their diverse and unexpected roles in the metabolism of cholesterol and lipids and the production of secondary metabolites. Biochemical and biophysical studies of these enzymes provided knowledge of their active site properties that may be exploited for drug discovery. Therefore, with the prospect of defining novel functions and identifying novel drug targets, characterisations of the remaining orphan Mtb P450s is of interest. M. tuberculosis CYP141A1 and CYP143A1 are orphan enzymes with unknown physiological function in Mtb which is characterised in this study through use of various spectroscopic and biophysical techniques. Interestingly, CYP141A1 can be expressed in form of which 54 amino acids (Del54CYP141A1) are deleted from the N-terminus. Although Del54CYP141A1 still retain spectroscopic characteristics, this form of P450 cannot be crystallized. Optimisation of full-length CYP141A1 buffer composition resulted to the formation of reproducible crystals and determination of CYP141A1 structure. Spectroscopic and structural characterisations presented in this thesis revealed many characteristics of CYP141A1 and CYP143A1 are comparable to previous Mtb P450s reported to date. CYP141A1 and CYP143A1 active site consist of b-type heme iron ligated by cysteine residue and a water molecule at its proximal and distal face, respectively. Both enzymes bind tightly to azole antifungal drugs highlighting their potential as a drug target. In addition, fragment-based screening applied to CYP141A1 and CYP143A1 provided the starting point for the development of potent, isoform-specific inhibitors for both orphan Mtb P450 enzymes. The first crystal structure of CYP141A1 and identification of new fragment binders of CYP141A1 and CYP143A1 are presented in this thesis. Overall, this research remains significant in providing new knowledge on the spectroscopic and structural properties of the M. tuberculosis P450s CYP141A1 and CYP143A1. Advisors/Committee Members: LEYS, DAVID D, Munro, Andrew, Leys, David.

Subjects/Keywords: Tuberculosis; Cytochrome P450; Fragment-based drug discovery

10 more images…

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Nisbar, N. D. b. (2018). Characterisation of orphan cytochrome P450s from Mycobacterium tuberculosis H37Rv. (Doctoral Dissertation). University of Manchester. Retrieved from http://www.manchester.ac.uk/escholar/uk-ac-man-scw:313431

Chicago Manual of Style (16^th Edition):

Nisbar, Nur Dayana binti. “Characterisation of orphan cytochrome P450s from Mycobacterium tuberculosis H37Rv.” 2018. Doctoral Dissertation, University of Manchester. Accessed April 19, 2021. http://www.manchester.ac.uk/escholar/uk-ac-man-scw:313431.

MLA Handbook (7^th Edition):

Nisbar, Nur Dayana binti. “Characterisation of orphan cytochrome P450s from Mycobacterium tuberculosis H37Rv.” 2018. Web. 19 Apr 2021.

Vancouver:

Nisbar NDb. Characterisation of orphan cytochrome P450s from Mycobacterium tuberculosis H37Rv. [Internet] [Doctoral dissertation]. University of Manchester; 2018. [cited 2021 Apr 19]. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:313431.

Council of Science Editors:

Nisbar NDb. Characterisation of orphan cytochrome P450s from Mycobacterium tuberculosis H37Rv. [Doctoral Dissertation]. University of Manchester; 2018. Available from: http://www.manchester.ac.uk/escholar/uk-ac-man-scw:313431

Vanderbilt University

12. Albertolle, Matthew Edward. SULFENYLATION OF CYTOCHROMES P450 IN RESPONSE TO REDOX ALTERATION.

Degree: PhD, Biochemistry, 2019, Vanderbilt University

URL: http://hdl.handle.net/1803/10450

► Mammalian cytochrome P450 (P450) enzymes catalyze complex reactions involved in the biosynthesis of endogenous metabolites such as steroids, vitamins, and hormones. Additionally, several enzymes in… (more)

Subjects/Keywords: Cytochrome P450; Redox; Enzymology; Proteomics; Sulfenic Acid

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Albertolle, M. E. (2019). SULFENYLATION OF CYTOCHROMES P450 IN RESPONSE TO REDOX ALTERATION. (Doctoral Dissertation). Vanderbilt University. Retrieved from http://hdl.handle.net/1803/10450

Chicago Manual of Style (16^th Edition):

Albertolle, Matthew Edward. “SULFENYLATION OF CYTOCHROMES P450 IN RESPONSE TO REDOX ALTERATION.” 2019. Doctoral Dissertation, Vanderbilt University. Accessed April 19, 2021. http://hdl.handle.net/1803/10450.

MLA Handbook (7^th Edition):

Albertolle, Matthew Edward. “SULFENYLATION OF CYTOCHROMES P450 IN RESPONSE TO REDOX ALTERATION.” 2019. Web. 19 Apr 2021.

Vancouver:

Albertolle ME. SULFENYLATION OF CYTOCHROMES P450 IN RESPONSE TO REDOX ALTERATION. [Internet] [Doctoral dissertation]. Vanderbilt University; 2019. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/1803/10450.

Council of Science Editors:

Albertolle ME. SULFENYLATION OF CYTOCHROMES P450 IN RESPONSE TO REDOX ALTERATION. [Doctoral Dissertation]. Vanderbilt University; 2019. Available from: http://hdl.handle.net/1803/10450

Penn State University

13. Yosca, Timothy Howard. Understanding C-H Bond Activation in Heme Proteins: The Importance of the Ferryl pKa.

Degree: 2012, Penn State University

URL: https://submit-etda.libraries.psu.edu/catalog/16041

► The major focus of the Green group involves the study of C-H bond activation by heme proteins and the elucidation of the factors giving rise… (more)

▼ The major focus of the Green group involves the study of C-H bond activation by heme proteins and the elucidation of the factors giving rise to this potent chemistry. Because only thiolate ligated heme enzymes such as cytochrome P450 (P450), chloroperoxidase (CPO), and aromatic peroxygenase (APO) are capable of difficult hydrocarbon oxidations, we believe that Nature has specifically chosen the thiolate ligand in order to facilitate H-atom abstraction. Current evidence suggests that the strong donating nature of the thiolate elevates the pKa of the compound II (ferryl) species, and could be the reason for the increased driving force. Conversely, it is proposed that a lower ferryl pKa in histidine and tyrosine ligated heme enzymes significantly decreases the reactivity, thus preventing C-H bond activation. In an effort to provide concrete evidence for the magnitude of the proposed driving force, we set out to quantitate the thermodynamic “pKa” parameter in histidine, thiolate, and tyrosine ligated heme systems. While it is has been shown that the thiolate ligated P450-II and CPO-II intermediates are basic in nature, there is much controversy over the protonation status of histidine ligated ferryls. X-ray crystallographic studies favor long Fe-O bond lengths (~1.85 Å), indicating protonated (FeIV-OH) moieties, while EXAFS report much shorter distances (~1.65 Å), classifying them as authentic FeIV=O intermediates. If histidine ligated ferryls are basic, then theory suggests that they could be able to activate C-H bonds, yet no experimental evidence supports this claim. In order to investigate this controversy, we explored the protonation status of the histidine ligated myoglobin compound II (Mb-II) intermediate over a wide pH range (9.5→3.9). Using a battery of spectroscopic techniques (Mössbauer, Resonance Raman, and EXAFS) our results definitively show that Mb-II is an authentic FeIV oxo with a pKa ≤ 2.65. We can infer from this study that all histidine ligated ferryls are FeIV oxos (at physiological pH), and that previous crystallographic reports for protonated ferryls in these systems are a direct result of radiation damage. Although we could only establish an upper limit for the pKa in histidine ligated proteins, we were able to directly measure the compound II pKa in both thiolate (CYP158A2 with pKa ~ 12) and tyrosine (Helicobacter pylori catalase with pKa ~ 13) ligated systems. These values represent the first ever reported pKas for any FeIV-OH species. Relative to histidine ligated enzymes, the elevated pKa in thiolate and tyrosine ligated ferryls could account for an additional ~ 13 kcals of driving force in a given hydrocarbon oxidation. Unexpectedly, tyrosine ligated hemes have higher ferryl pKas than their thiolate ligated counterparts, suggesting that CPO, APO, and P450 may not be the only heme proteins capable of C-H bond activation. Advisors/Committee Members: Michael Thomas Green, Dissertation Advisor/Co-Advisor, Joseph M Bollinger Jr., Committee Member, Squire J Booker, Committee Member, Ming Tien, Committee Member.

Subjects/Keywords: cytochrome p450; compound II; ferryl pKa

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Yosca, T. H. (2012). Understanding C-H Bond Activation in Heme Proteins: The Importance of the Ferryl pKa. (Thesis). Penn State University. Retrieved from https://submit-etda.libraries.psu.edu/catalog/16041

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Yosca, Timothy Howard. “Understanding C-H Bond Activation in Heme Proteins: The Importance of the Ferryl pKa.” 2012. Thesis, Penn State University. Accessed April 19, 2021. https://submit-etda.libraries.psu.edu/catalog/16041.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Yosca, Timothy Howard. “Understanding C-H Bond Activation in Heme Proteins: The Importance of the Ferryl pKa.” 2012. Web. 19 Apr 2021.

Vancouver:

Yosca TH. Understanding C-H Bond Activation in Heme Proteins: The Importance of the Ferryl pKa. [Internet] [Thesis]. Penn State University; 2012. [cited 2021 Apr 19]. Available from: https://submit-etda.libraries.psu.edu/catalog/16041.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Yosca TH. Understanding C-H Bond Activation in Heme Proteins: The Importance of the Ferryl pKa. [Thesis]. Penn State University; 2012. Available from: https://submit-etda.libraries.psu.edu/catalog/16041

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Saskatchewan

14. Boyd, Erin Margaret Rose. Phase I and II enzyme induction and inhibition by secoisolariciresinol diglucoside and it's aglycone.

Degree: 2007, University of Saskatchewan

URL: http://hdl.handle.net/10388/etd-04262007-161734

► The flaxseed lignan, secoisolariciresinol diglucoside (SDG), and its aglycone, secoisolariciresinol (SECO), have demonstrated benefits in the treatment and/or prevention of cancer, diabetes and cardiovascular disease.… (more)

▼ The flaxseed lignan, secoisolariciresinol diglucoside (SDG), and its aglycone, secoisolariciresinol (SECO), have demonstrated benefits in the treatment and/or prevention of cancer, diabetes and cardiovascular disease. In order for the lignans to be used therapeutically, the safety of administration alone and in conjunction with other drugs must be determined. The primary cause of drug interactions is induction and inhibition of cytochrome P450 (CYP) and phase II enzymes. A preliminary screen was conducted to assess the potential for SECO and SDG to cause CYP inhibition. A method was established to assess for CYP, glutathione-S-transferase (GST) and uridine diphosphate-glucuronosyltransferase (UGT) induction in rat primary hepatocytes by real-time reverse transcription-polymerase chain reaction (RT-PCR).Preliminary assessments of inhibition measured the metabolism of testosterone to 6β-, 16α- and 2α-hydroxytestosterone, which corresponds to CYP3A, 2B/2C11 and 2C11 enzyme activity in rat hepatic microsomes by a validated high performance liquid chromatography (HPLC) method. Irreversible inhibition studies found that SDG is not an inhibitor of these isoforms up to 1000 μM. Secoisolariciresinol caused reversible inhibition of 6β-hydroxytestosterone at all testosterone concentrations, with an IC50 (inhibitor concentration causing 50% inhibition of enzyme) between 400 and 800 μM. Over the range of SECO concentrations tested, 10 – 1600 μM, 6β-hydroxytestosterone formation was reduced to 95 – 29% of control levels at 50 μM testosterone.Secoisolariciresinol caused a concentration-dependent increase in 16α-hydroxytestosterone formation at 50 μM testosterone. At 10 μM SECO, there was 90% of control activity, but at 1600 μM metabolite formation was 172% of control. The formation of 2α-hydroxytestosterone was not affected at any testosterone or inhibitor concentration. Thus, SECO appears to be a CYP3A inhibitor and a CYP2B activator at testosterone KM levels. The mechanism of reversible inhibition could not be determined due to the possibility of non-Michaelis-Menten kinetics observed with CYP3A inhibition and CYP2B activation. The gold standard in vitro model to assess induction is primary hepatocytes. A method was established that allowed for the isolation and culture of these cells. Positive controls caused induction of CYP mRNA levels after 24 hours treatment, demonstrating the ability of enzyme induction in the test system. Primers for real-time RT-PCR were designed that amplified CYP1A1, 1A2, 2B1, 2C11, 2C13, 2D1, 2D2, 3A1 and 3A2, GSTA2, A5 and P1, and UGT1A1, 1A7, 1A8, 2B1 and 2B12 genes. A preliminary assessment of transcriptional upregulation of drug metabolizing enzymes by SECO and SDG can be assessed in isolated and cultured rat primary hepatocytes. Advisors/Committee Members: Krol, Ed S., Alcorn, Jane, Janz, David M., Blakley, Barry R..

Subjects/Keywords: Cytochrome P450; Flaxseed

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Boyd, E. M. R. (2007). Phase I and II enzyme induction and inhibition by secoisolariciresinol diglucoside and it's aglycone. (Thesis). University of Saskatchewan. Retrieved from http://hdl.handle.net/10388/etd-04262007-161734

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Boyd, Erin Margaret Rose. “Phase I and II enzyme induction and inhibition by secoisolariciresinol diglucoside and it's aglycone.” 2007. Thesis, University of Saskatchewan. Accessed April 19, 2021. http://hdl.handle.net/10388/etd-04262007-161734.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Boyd, Erin Margaret Rose. “Phase I and II enzyme induction and inhibition by secoisolariciresinol diglucoside and it's aglycone.” 2007. Web. 19 Apr 2021.

Vancouver:

Boyd EMR. Phase I and II enzyme induction and inhibition by secoisolariciresinol diglucoside and it's aglycone. [Internet] [Thesis]. University of Saskatchewan; 2007. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/10388/etd-04262007-161734.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Boyd EMR. Phase I and II enzyme induction and inhibition by secoisolariciresinol diglucoside and it's aglycone. [Thesis]. University of Saskatchewan; 2007. Available from: http://hdl.handle.net/10388/etd-04262007-161734

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Adelaide

15. Child, Stella Agnes. Deciphering electron transfer and cytochrome P450 activity in Mycobacterium marinum.

Degree: 2018, University of Adelaide

URL: http://hdl.handle.net/2440/118202

► Cytochrome P450s are haem-monooxygenase enzymes, responsible for the catalytic hydroxylation of a large variety of organic molecules. The bacterium Mycobacterium marinum, has a larger genome… (more)

▼ Cytochrome P450s are haem-monooxygenase enzymes, responsible for the catalytic hydroxylation of a large variety of organic molecules. The bacterium Mycobacterium marinum, has a larger genome than its close relatives, the causative agents of human tuberculosis (Mycobacterium tuberculosis) and Buruli ulcer (Mycobacterium ulcerans), which have undergone substantial reductive evolution. The genome of M. marinum contains an unusually large number of P450 genes (47). Twelve ferredoxin genes are associated with the CYPome and eleven of these are uncharacterised ferredoxins of the 3/4Fe-4S type. In their iron-sulfur cluster binding motif (CXX?XXC(X)nCP), these ferredoxins (Fdx1 – Fdx11) have non-standard residues at the ? position of the sequence. Instead of the cysteine residue expected of a [4Fe-4S] ferredoxin, or the alanine/glycine residue expected in a [3Fe-4S] ferredoxin, they contain histidine, asparagine, tyrosine, serine, threonine and phenylalanine residues. In the course of this work, they have been purified aerobically and anaerobically. When isolated anaerobically, three of these ferredoxins were determined, by non-denaturing ESI-MS and EPR to contain 3Fe-4S clusters. The reduction potentials for the three varied from +150 mV to -360 mV, which are highly anomalous for [3Fe-4S] ferredoxins. Similar ferredoxins were found to accompany P450s in the biosynthetic gene clusters of other bacteria, especially in Actinomycete species. These ferredoxins were demonstrated to support the activity of a number of the M. marinum P450s, some of which were from previously uncharacterised families. CYP147G1, in combination with the electron transfer partners Fdx3 and FdR1 was demonstrated to act as a ω-1 fatty acid hydroxylase. CYP147G1 selectivity favoured the ω carbon when branched methyl substrates were used. The same ferredoxin reductase, FdR1, was also shown to support the activity of CYP278A1 (with Fdx2), and CYP150A5 (with Fdx8), both of which were shown to regioselectively hydroxylate β-ionone. CYP150A5 binds terpenes and polycyclic substrates. An additional CYP150 enzyme, CYP150A6, was crystallised and structurally resolved to 1.6 Å in the substrate-free form. CYP268A2, when reconstituted with a non-native electron transfer chain, hydroxylated the branched fatty acetate derivatives, pseudoionone and geranyl acetate, at the terminal position. The structure of CYP268A2 with trans-pseudoionone bound in the active site was solved by X-ray crystallography to a resolution of 2.0 Å and from this the selectivity of the enzyme was rationalised. Several M. marinum P450s that have close counterparts in M. tuberculosis were selected for comparison, in order to investigate whether the substrate and inhibitor binding affinities were preserved between species. The P450s investigated were analogues of the steroid metabolising P450s in M. tuberculosis. CYP125A6 and CYP125A7 have a single counterpart in M. tuberculosis (CYP125A1). The sequence identity and cholesterol binding affinity of CYP125A7 indicates it more closely resembles… Advisors/Committee Members: Bell, Stephen (advisor), Pyke, Simon (advisor), School of Physical Sciences (school).

Subjects/Keywords: Electron transfer; cytochrome P450; mycobacteria; biocatalysis

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Child, S. A. (2018). Deciphering electron transfer and cytochrome P450 activity in Mycobacterium marinum. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/118202

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Child, Stella Agnes. “Deciphering electron transfer and cytochrome P450 activity in Mycobacterium marinum.” 2018. Thesis, University of Adelaide. Accessed April 19, 2021. http://hdl.handle.net/2440/118202.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Child, Stella Agnes. “Deciphering electron transfer and cytochrome P450 activity in Mycobacterium marinum.” 2018. Web. 19 Apr 2021.

Vancouver:

Child SA. Deciphering electron transfer and cytochrome P450 activity in Mycobacterium marinum. [Internet] [Thesis]. University of Adelaide; 2018. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/2440/118202.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Child SA. Deciphering electron transfer and cytochrome P450 activity in Mycobacterium marinum. [Thesis]. University of Adelaide; 2018. Available from: http://hdl.handle.net/2440/118202

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Toronto

16. Tsai, Chieh. The Effects of Uremic Serum from Hemodialysis Patients on Hepatic Cyochrome P450 and VKORC1 Gene Expression in Primary Human Hepatocytes.

Degree: 2017, University of Toronto

URL: http://hdl.handle.net/1807/77912

►

Warfarin is frequently prescribed to patients with atrial fibrillation (AF) who are on hemodialysis (HD) for stroke prevention regardless of conflicting evidence showing unclear benefits… (more)

Subjects/Keywords: Cytochrome P450; Hemodialysis; VKORC1; Warfarin; 0572

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Tsai, C. (2017). The Effects of Uremic Serum from Hemodialysis Patients on Hepatic Cyochrome P450 and VKORC1 Gene Expression in Primary Human Hepatocytes. (Masters Thesis). University of Toronto. Retrieved from http://hdl.handle.net/1807/77912

Chicago Manual of Style (16^th Edition):

Tsai, Chieh. “The Effects of Uremic Serum from Hemodialysis Patients on Hepatic Cyochrome P450 and VKORC1 Gene Expression in Primary Human Hepatocytes.” 2017. Masters Thesis, University of Toronto. Accessed April 19, 2021. http://hdl.handle.net/1807/77912.

MLA Handbook (7^th Edition):

Tsai, Chieh. “The Effects of Uremic Serum from Hemodialysis Patients on Hepatic Cyochrome P450 and VKORC1 Gene Expression in Primary Human Hepatocytes.” 2017. Web. 19 Apr 2021.

Vancouver:

Tsai C. The Effects of Uremic Serum from Hemodialysis Patients on Hepatic Cyochrome P450 and VKORC1 Gene Expression in Primary Human Hepatocytes. [Internet] [Masters thesis]. University of Toronto; 2017. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/1807/77912.

Council of Science Editors:

Tsai C. The Effects of Uremic Serum from Hemodialysis Patients on Hepatic Cyochrome P450 and VKORC1 Gene Expression in Primary Human Hepatocytes. [Masters Thesis]. University of Toronto; 2017. Available from: http://hdl.handle.net/1807/77912

University of Illinois – Chicago

17. Zhang, Shu. Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner.

Degree: 2016, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/21572

► Small heterodimer partner (SHP) is a transcriptional corepressor of a number of ligand regulated nuclear receptors (NR) and orphan receptors, and represses their target genes… (more)

▼ Small heterodimer partner (SHP) is a transcriptional corepressor of a number of ligand regulated nuclear receptors (NR) and orphan receptors, and represses their target genes expression. Studying transcriptional regulation mechanism of important DMEs can help better understand and predict of the elimination of drugs, and effectively achieve personalized medicine. Farnesoid X receptor (FXR) functions as a regulator of bile acid and lipid homeostasis, and is recognized as a promising therapeutic target for metabolic diseases. SHP is the target gene of several signaling pathways, and various inducers significantly increase its expression. In Chapter 1, we investigated the effect of FXR activation on the expression of the major drug-metabolizing enzyme, CYP3A4. The results in Chapter 1 showed that in human hepatocytes, treatment of GW4064 (1 μM) for 48 hours resulted in 75% decrease in CYP3A4 mRNA expression and 25% decrease in CYP3A4 activity, accompanied by ~3-fold increase in SHP mRNA expression. In HepG2 cells, SHP repressed transactivation of CYP3A4 promoter by pregnane X receptor (PXR), constitutive androstane receptor (CAR), and glucocorticoid receptor (GR). Interestingly, GW4064 did not repress expression of CYP2B6, another target gene of PXR and CAR; GW4064 was shown to enhance CYP2B6 promoter activity. In conclusion, GW4064 represses CYP3A4 expression in human hepatocytes, potentially through upregulation of SHP expression and subsequent repression of CYP3A4 promoter activity. Clinically significant drug-drug interaction involving FXR agonists and CYP3A4 substrates may occur. In Chapter 2, we characterized the effect of ATRA, another potential inducer of SHP, on CYP2D6 expression in vitro and in vivo. Results showed in both human hepatocytes and transgenic mices, CYP2D6 mRNA expression level was significantly repressed by ~70% in vitro, and by ~50% in vivo. The repressed CYP2D6 expression is accompanied by induced SHP expression which was elevated by ~3-fold in vitro and ~5-fold in vivo, respectively. The correlation between SHP and CYP2D6 was further confirmed using mice with Tg-CYP2D6 with Shp knockout compared with Tg- CYP2D6 wild-type mice. Overall, the results indicated that SHP is a key regulator in ATRA- induced CYP2D6 repression. Advisors/Committee Members: Jeong, Hyunyoung (advisor), Hong, Seungpyo (committee member), Larsen, Karl (committee member), Jeong, Hyunyoung (chair).

Subjects/Keywords: Cytochrome P450; CYP3A4; CYP2D6; FXR; ATRA

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhang, S. (2016). Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/21572

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zhang, Shu. “Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner.” 2016. Thesis, University of Illinois – Chicago. Accessed April 19, 2021. http://hdl.handle.net/10027/21572.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zhang, Shu. “Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner.” 2016. Web. 19 Apr 2021.

Vancouver:

Zhang S. Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner. [Internet] [Thesis]. University of Illinois – Chicago; 2016. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/10027/21572.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhang S. Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner. [Thesis]. University of Illinois – Chicago; 2016. Available from: http://hdl.handle.net/10027/21572

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

18. Zhang, Shu. Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner.

Degree: 2016, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/21629

► Small heterodimer partner (SHP) is a transcriptional corepressor of a number of ligand regulated nuclear receptors (NR) and orphan receptors, and represses their target genes… (more)

▼ Small heterodimer partner (SHP) is a transcriptional corepressor of a number of ligand regulated nuclear receptors (NR) and orphan receptors, and represses their target genes expression. Studying transcriptional regulation mechanism of important DMEs can help better understand and predict of the elimination of drugs, and effectively achieve personalized medicine. Farnesoid X receptor (FXR) functions as a regulator of bile acid and lipid homeostasis, and is recognized as a promising therapeutic target for metabolic diseases. SHP is the target gene of several signaling pathways, and various inducers significantly increase its expression. In Chapter 1, we investigated the effect of FXR activation on the expression of the major drug-metabolizing enzyme, CYP3A4. The results in Chapter 1 showed that in human hepatocytes, treatment of GW4064 (1 μM) for 48 hours resulted in 75% decrease in CYP3A4 mRNA expression and 25% decrease in CYP3A4 activity, accompanied by ~3-fold increase in SHP mRNA expression. In HepG2 cells, SHP repressed transactivation of CYP3A4 promoter by pregnane X receptor (PXR), constitutive androstane receptor (CAR), and glucocorticoid receptor (GR). Interestingly, GW4064 did not repress expression of CYP2B6, another target gene of PXR and CAR; GW4064 was shown to enhance CYP2B6 promoter activity. In conclusion, GW4064 represses CYP3A4 expression in human hepatocytes, potentially through upregulation of SHP expression and subsequent repression of CYP3A4 promoter activity. Clinically significant drug-drug interaction involving FXR agonists and CYP3A4 substrates may occur. In Chapter 2, we characterized the effect of ATRA, another potential inducer of SHP, on CYP2D6 expression in vitro and in vivo. Results showed in both human hepatocytes and transgenic mices, CYP2D6 mRNA expression level was significantly repressed by ~70% in vitro, and by ~50% in vivo. The repressed CYP2D6 expression is accompanied by induced SHP expression which was elevated by ~3-fold in vitro and ~5-fold in vivo, respectively. The correlation between SHP and CYP2D6 was further confirmed using mice with Tg-CYP2D6 with Shp knockout compared with Tg- CYP2D6 wild-type mice. Overall, the results indicated that SHP is a key regulator in ATRA- induced CYP2D6 repression. Advisors/Committee Members: Jeong, Hyunyoung (advisor), Hong, Seungpyo (committee member), Larsen, Karl (committee member), Jeong, Hyunyoung (chair).

Subjects/Keywords: Cytochrome P450; CYP3A4; CYP2D6; FXR; ATRA

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhang, S. (2016). Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/21629

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zhang, Shu. “Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner.” 2016. Thesis, University of Illinois – Chicago. Accessed April 19, 2021. http://hdl.handle.net/10027/21629.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zhang, Shu. “Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner.” 2016. Web. 19 Apr 2021.

Vancouver:

Zhang S. Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner. [Internet] [Thesis]. University of Illinois – Chicago; 2016. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/10027/21629.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhang S. Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner. [Thesis]. University of Illinois – Chicago; 2016. Available from: http://hdl.handle.net/10027/21629

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Chicago

19. Zhang, Shu. Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner.

Degree: 2016, University of Illinois – Chicago

URL: http://hdl.handle.net/10027/21630

► Small heterodimer partner (SHP) is a transcriptional corepressor of a number of ligand regulated nuclear receptors (NR) and orphan receptors, and represses their target genes… (more)

▼ Small heterodimer partner (SHP) is a transcriptional corepressor of a number of ligand regulated nuclear receptors (NR) and orphan receptors, and represses their target genes expression. Studying transcriptional regulation mechanism of important DMEs can help better understand and predict of the elimination of drugs, and effectively achieve personalized medicine. Farnesoid X receptor (FXR) functions as a regulator of bile acid and lipid homeostasis, and is recognized as a promising therapeutic target for metabolic diseases. SHP is the target gene of several signaling pathways, and various inducers significantly increase its expression. In Chapter 1, we investigated the effect of FXR activation on the expression of the major drug-metabolizing enzyme, CYP3A4. The results in Chapter 1 showed that in human hepatocytes, treatment of GW4064 (1 μM) for 48 hours resulted in 75% decrease in CYP3A4 mRNA expression and 25% decrease in CYP3A4 activity, accompanied by ~3-fold increase in SHP mRNA expression. In HepG2 cells, SHP repressed transactivation of CYP3A4 promoter by pregnane X receptor (PXR), constitutive androstane receptor (CAR), and glucocorticoid receptor (GR). Interestingly, GW4064 did not repress expression of CYP2B6, another target gene of PXR and CAR; GW4064 was shown to enhance CYP2B6 promoter activity. In conclusion, GW4064 represses CYP3A4 expression in human hepatocytes, potentially through upregulation of SHP expression and subsequent repression of CYP3A4 promoter activity. Clinically significant drug-drug interaction involving FXR agonists and CYP3A4 substrates may occur. In Chapter 2, we characterized the effect of ATRA, another potential inducer of SHP, on CYP2D6 expression in vitro and in vivo. Results showed in both human hepatocytes and transgenic mices, CYP2D6 mRNA expression level was significantly repressed by ~70% in vitro, and by ~50% in vivo. The repressed CYP2D6 expression is accompanied by induced SHP expression which was elevated by ~3-fold in vitro and ~5-fold in vivo, respectively. The correlation between SHP and CYP2D6 was further confirmed using mice with Tg-CYP2D6 with Shp knockout compared with Tg- CYP2D6 wild-type mice. Overall, the results indicated that SHP is a key regulator in ATRA- induced CYP2D6 repression. Advisors/Committee Members: Jeong, Hyunyoung (advisor), Hong, Seungpyo (committee member), Larsen, Karl (committee member), Jeong, Hyunyoung (chair).

Subjects/Keywords: Cytochrome P450; CYP3A4; CYP2D6; FXR; ATRA

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Zhang, S. (2016). Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner. (Thesis). University of Illinois – Chicago. Retrieved from http://hdl.handle.net/10027/21630

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Zhang, Shu. “Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner.” 2016. Thesis, University of Illinois – Chicago. Accessed April 19, 2021. http://hdl.handle.net/10027/21630.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Zhang, Shu. “Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner.” 2016. Web. 19 Apr 2021.

Vancouver:

Zhang S. Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner. [Internet] [Thesis]. University of Illinois – Chicago; 2016. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/10027/21630.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Zhang S. Transcriptional Regulation of CYP3A4 and CYP2D6 by Small Heterodimer Partner. [Thesis]. University of Illinois – Chicago; 2016. Available from: http://hdl.handle.net/10027/21630

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Manchester

20. Driscoll, Max. Investigating orphan cytochromes P450 from Mycobacterium tuberculosis : the search for potential drug targets.

Degree: PhD, 2011, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/investigating-orphan-cytochromes-p450-from-mycobacterium-tuberculosis-the-search-for-potential-drug-targets(58eef811-4e97-4bfa-83ba-46be1a48c9f5).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538488

► Tuberculosis (TB) is a disease that the World Health Organisation (WHO) regards as a global pandemic. There is a great need for new drugs to… (more)

▼ Tuberculosis (TB) is a disease that the World Health Organisation (WHO) regards as a global pandemic. There is a great need for new drugs to combat this threat. Drug resistant strains of the causative agent, Mycobacterium tuberculosis (Mtb), have increased the urgency of this quest for novel anti-mycobacterial medicines. Publication of the Mtb genome sequence revealed a large number of cytochrome P450 (CYP) enzymes [Cole, S. T. et al. 1998]. These mono-oxygenase enzymes have been studied for many years and are responsible for metabolic functions in every kingdom of life. Research on the Mtb P450s to date has highlighted several of them as having critcal roles within the organism. CYP121 and CYP128 have been implicated as essential through gene knockout studies. It has been demonstrated that CYP125 is not essential for viability. However, it is part of a gene cluster highly important for Mtb infectivity and virulence. Due to the prospective importance of P450s to Mtb, this group of enzymes is under investigation as a source of novel drug targets. CYP142 was discovered as a potential drug target after it was located to a gene cluster involved in cholesterol catabolism during Mtb dormancy. As part of this PhD project, it was demonstrated that CYP142 performs an almost identical role to that reported for CYP125. These enzymes both perform C27 hydroxylation and carboxylation of the cholesterol side chain. However, variations in the level of oxidation have been identified, dependent upon the redox system with which these P450s are associated. A crystal structure of CYP142 showing high similarity in active site architecture to CYP125 supports the physiological role of CYP142 in cholesterol catabolism. Combining this with in vitro data which demonstrates that CYP142 possesses high affinity for a range of azole anti-fungal agents [Ahmad, Z. et al. 2005, 2006] supports the suggestion that it is a candidate target for the next generation of anti-mycobacterial drugs. CYP144 was highlighted as being important during the latent phase of Mtb growth, a phase that is not targeted by any of the current antimycobacterials. Work performed as part of this PhD has shown that many characteristics of CYP144 are highly comparable to those reported for other MtbP450s. CYP144 shows high affinity and specificity towards many azole molecules. Econazole, clotrimazole and miconazole have repeatedly been shown to bind to MtbP450s, including CYP144 and CYP142, with high affinity and are excellent potential candidates as novel anti-mycobacterial agents. An N-terminally truncated form of CYP144, CYP144-T, has been investigated in the pursuit of a CYP144 crystal structure. It is hoped that this will enable the elucidation of a physiological role for CYP144. Both CYP142 and CYP144 have demonstrated biochemical and biophysical characteristics that contribute to our knowledge of P450 enzymes. This PhD has established that CYP142 exhibits an equilibrium between P450 and P420 species in its CO-bound, ferrous form. A conversion from P420, and stabilisation…

Subjects/Keywords: 579; Tuberculosis; Mycobacterium; Mtb; P450; Cytochrome; CYP

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Driscoll, M. (2011). Investigating orphan cytochromes P450 from Mycobacterium tuberculosis : the search for potential drug targets. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/investigating-orphan-cytochromes-p450-from-mycobacterium-tuberculosis-the-search-for-potential-drug-targets(58eef811-4e97-4bfa-83ba-46be1a48c9f5).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538488

Chicago Manual of Style (16^th Edition):

Driscoll, Max. “Investigating orphan cytochromes P450 from Mycobacterium tuberculosis : the search for potential drug targets.” 2011. Doctoral Dissertation, University of Manchester. Accessed April 19, 2021. https://www.research.manchester.ac.uk/portal/en/theses/investigating-orphan-cytochromes-p450-from-mycobacterium-tuberculosis-the-search-for-potential-drug-targets(58eef811-4e97-4bfa-83ba-46be1a48c9f5).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538488.

MLA Handbook (7^th Edition):

Driscoll, Max. “Investigating orphan cytochromes P450 from Mycobacterium tuberculosis : the search for potential drug targets.” 2011. Web. 19 Apr 2021.

Vancouver:

Driscoll M. Investigating orphan cytochromes P450 from Mycobacterium tuberculosis : the search for potential drug targets. [Internet] [Doctoral dissertation]. University of Manchester; 2011. [cited 2021 Apr 19]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/investigating-orphan-cytochromes-p450-from-mycobacterium-tuberculosis-the-search-for-potential-drug-targets(58eef811-4e97-4bfa-83ba-46be1a48c9f5).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538488.

Council of Science Editors:

Driscoll M. Investigating orphan cytochromes P450 from Mycobacterium tuberculosis : the search for potential drug targets. [Doctoral Dissertation]. University of Manchester; 2011. Available from: https://www.research.manchester.ac.uk/portal/en/theses/investigating-orphan-cytochromes-p450-from-mycobacterium-tuberculosis-the-search-for-potential-drug-targets(58eef811-4e97-4bfa-83ba-46be1a48c9f5).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.538488

University of Manchester

21. Elliott, Peter. Characterisation of the unique Campylobacter jejuni cytochrome P450, CYP172A1.

Degree: PhD, 2013, University of Manchester

URL: https://www.research.manchester.ac.uk/portal/en/theses/characterisation-of-the-unique-campylobacter-jejuni-cytochrome-p450-cyp172a1(760b6cf4-f951-4642-9d99-b05b9a13ede2).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607029

► Campylobacter jejuni is a leading cause of food poisoning and according to the World Health Organisation accounts for majority of the 4.5 billion cases of… (more)

▼ Campylobacter jejuni is a leading cause of food poisoning and according to the World Health Organisation accounts for majority of the 4.5 billion cases of global food poisoning each year. Genome sequencing by Parkhill et al. (2000) identified a gene, cj1411c, which is thought to encode a lone cytochrome P450, CYP172A1. In this thesis the role of CYP172A1 was studied using in vivo and in vitro techniques. The genomic location of cj1411c is adjacent to the capsular biosynthetic genes. The capsular and P450 genes are conserved in some species of Campylobacter and Helicobacter, as well as in Comamonas testosteroni. Importantly, this work has demonstrated that the P450 gene is expressed in two well characterised laboratory C. jejuni strains, 11168H and 81-176. Protein production was disrupted using insertional knockout mutagenesis, which allowed for investigations into the role of the enzyme in the host. Alterations to the observed autoagglutination rate and growth characteristics indicated that CYP172A1 has a role in modifying the bacterial surface. The insertional knockout mutant also resulted in cells which were more susceptible to detergent-like compounds (e.g. polymyxin B and sodium deoxycholate). In a previous report, it was suggested that the loss of the P450 function resulted in bacteria which were “shorter and fatter”, compared to wild type cells, but this thesis could find no evidence of such a phenomenon. CYP172A1 was successfully purified using recombinant expression in E. coli to enable biochemical and biophysical characterisation in vitro. CYP172A1 contains a typical P450 cysteine thiolate coordination to the heme iron, and exists in a low spin ferric heme state under neutral buffer conditions. The P450 was found to self aggregate, and despite rigorous investigations the cause of this aggregation was not fully established. Despite this issue, CYP172A1 was shown to bind to a wide range of P450 inhibitor-type compounds, with econazole displaying the tightest binding affinity (Kd = 100 nM). Identification of substrate-like compounds was achieved using high throughput compound screening, and a number of organic compounds were identified and shown to bind CYP172A1, inducing heme iron absorbance changes typical of either P450 inhibitors or substrates. Optical titrations for these molecules indicated that their CYP172A1 Kd values were in the low micromolar range. The catalytic capability of CYP172A1 was successfully demonstrated by providing the P450 with non native redox partners to oxidise one of such substrate-like compound (213071), resulting in the sulfoxidation of this compound.

Subjects/Keywords: 616.9; Cytochrome P450; CYP172A1; Campylobacter jejuni; Capsule

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Elliott, P. (2013). Characterisation of the unique Campylobacter jejuni cytochrome P450, CYP172A1. (Doctoral Dissertation). University of Manchester. Retrieved from https://www.research.manchester.ac.uk/portal/en/theses/characterisation-of-the-unique-campylobacter-jejuni-cytochrome-p450-cyp172a1(760b6cf4-f951-4642-9d99-b05b9a13ede2).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607029

Chicago Manual of Style (16^th Edition):

Elliott, Peter. “Characterisation of the unique Campylobacter jejuni cytochrome P450, CYP172A1.” 2013. Doctoral Dissertation, University of Manchester. Accessed April 19, 2021. https://www.research.manchester.ac.uk/portal/en/theses/characterisation-of-the-unique-campylobacter-jejuni-cytochrome-p450-cyp172a1(760b6cf4-f951-4642-9d99-b05b9a13ede2).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607029.

MLA Handbook (7^th Edition):

Elliott, Peter. “Characterisation of the unique Campylobacter jejuni cytochrome P450, CYP172A1.” 2013. Web. 19 Apr 2021.

Vancouver:

Elliott P. Characterisation of the unique Campylobacter jejuni cytochrome P450, CYP172A1. [Internet] [Doctoral dissertation]. University of Manchester; 2013. [cited 2021 Apr 19]. Available from: https://www.research.manchester.ac.uk/portal/en/theses/characterisation-of-the-unique-campylobacter-jejuni-cytochrome-p450-cyp172a1(760b6cf4-f951-4642-9d99-b05b9a13ede2).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607029.

Council of Science Editors:

Elliott P. Characterisation of the unique Campylobacter jejuni cytochrome P450, CYP172A1. [Doctoral Dissertation]. University of Manchester; 2013. Available from: https://www.research.manchester.ac.uk/portal/en/theses/characterisation-of-the-unique-campylobacter-jejuni-cytochrome-p450-cyp172a1(760b6cf4-f951-4642-9d99-b05b9a13ede2).html ; http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.607029

University of Washington

22. Okialda, Krystle Alarcon. Screening for MicroRNA Regulators of an Orphan Cytochrome P450 4V2 (CYP4V2).

Degree: 2012, University of Washington

URL: http://hdl.handle.net/1773/20797

► Cytochrome P450 4V2 (CYP4V2) is a gene linked to the ocular disease Bietti's Crystalline Dystrophy (BCD). Sequence analysis of CYP4V2 in BCD patients identified potentially… (more)

▼ Cytochrome P450 4V2 (CYP4V2) is a gene linked to the ocular disease Bietti's Crystalline Dystrophy (BCD). Sequence analysis of CYP4V2 in BCD patients identified potentially disruptive exonic and intronic mutations. Patients with BCD have characteristic crystalline deposits in the cornea and retina, retinal pigmented epithelium degeneration and sclerosis of the choroidal capillaries. Visual defects progress from nyctalopia to eventual blindness. In addition to vision loss, BCD patients exhibit crystalline deposits in fibroblasts and lymphocytes and alterations in plasma fatty acids. CYP4 family enzymes are associated with metabolism of endogenous substrates, including omega-hydroxylation of fatty acids; CYP4V2 is also an omega-hydroxylase of fatty acids, including docosanoids. While progress has been made in determining the activity and function of CYP4V2, regulation of its expression has not been well-examined. Amongst the 57 CYP genes in humans, CYP4V2 stands out with regard to the length of the transcript 3' UTR, extending over 2.8 kb in comparison to 1.6 kb of coding sequence. This led to the hypothesis that CYP4V2 may be subject to epigenetic regulation by microRNAs. To test this, we selected human liver samples from the UW Liver Bank that had highest and lowest CYP4V2 mRNA and subjected them to microRNA microarray analysis (n=6 per group). We identified miR-146b-5p to be over-expressed in liver samples with lower CYP4V2 mRNA, a miRNA that has a potential binding site in the CYP4V2 mRNA 3'UTR. Western blot data showed CYP4V2 mRNA expression correlated with CYP4V2 protein expression (R² = 0.472, p = 0.0282) and CYP4V2 protein expression was negatively correlated with miR-146b-5p expression (R² = 0.4254, p = 0.041). Interestingly, miR-146b expression has been found to be up-regulated by Resolvin D1, a docosanoid signaling molecule involved in acute inflammation. This raises the question of what role CYP4V2 may have in docosanoid signaling pathways in healthy individuals and the effects of CYP4V2 mutations in BCD patients. Advisors/Committee Members: Kelly, Edward J (advisor).

Subjects/Keywords: Cytochrome P450; Epigenetics; MicroRNA; Molecular biology; Pharmaceutics

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Okialda, K. A. (2012). Screening for MicroRNA Regulators of an Orphan Cytochrome P450 4V2 (CYP4V2). (Thesis). University of Washington. Retrieved from http://hdl.handle.net/1773/20797

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Okialda, Krystle Alarcon. “Screening for MicroRNA Regulators of an Orphan Cytochrome P450 4V2 (CYP4V2).” 2012. Thesis, University of Washington. Accessed April 19, 2021. http://hdl.handle.net/1773/20797.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Okialda, Krystle Alarcon. “Screening for MicroRNA Regulators of an Orphan Cytochrome P450 4V2 (CYP4V2).” 2012. Web. 19 Apr 2021.

Vancouver:

Okialda KA. Screening for MicroRNA Regulators of an Orphan Cytochrome P450 4V2 (CYP4V2). [Internet] [Thesis]. University of Washington; 2012. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/1773/20797.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Okialda KA. Screening for MicroRNA Regulators of an Orphan Cytochrome P450 4V2 (CYP4V2). [Thesis]. University of Washington; 2012. Available from: http://hdl.handle.net/1773/20797

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

23. Kraisiri, KHIDKHAN. Toxicological studies on feline cytochrome P450 associated with environmental chemical exposures [an abstract of entire text].

Degree: 博士(獣医学), 獣医学, 2020, Hokkaido University

URL: http://hdl.handle.net/2115/79723

► Cats have been known to be extremely sensitive to chemical exposures. The knowledge of cytochrome P450 (CYP) expression involved in chemical exposure are necessary in… (more)

Subjects/Keywords: Cat; cytochrome P450; mRNA expression; PCBs

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Kraisiri, K. (2020). Toxicological studies on feline cytochrome P450 associated with environmental chemical exposures [an abstract of entire text]. (Thesis). Hokkaido University. Retrieved from http://hdl.handle.net/2115/79723

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Kraisiri, KHIDKHAN. “Toxicological studies on feline cytochrome P450 associated with environmental chemical exposures [an abstract of entire text].” 2020. Thesis, Hokkaido University. Accessed April 19, 2021. http://hdl.handle.net/2115/79723.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Kraisiri, KHIDKHAN. “Toxicological studies on feline cytochrome P450 associated with environmental chemical exposures [an abstract of entire text].” 2020. Web. 19 Apr 2021.

Vancouver:

Kraisiri K. Toxicological studies on feline cytochrome P450 associated with environmental chemical exposures [an abstract of entire text]. [Internet] [Thesis]. Hokkaido University; 2020. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/2115/79723.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Kraisiri K. Toxicological studies on feline cytochrome P450 associated with environmental chemical exposures [an abstract of entire text]. [Thesis]. Hokkaido University; 2020. Available from: http://hdl.handle.net/2115/79723

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

University of Illinois – Urbana-Champaign

24. Lenov, Ivan Lenkov. Methodologies for the analysis of membrane systems using lipid nanodiscs.

Degree: PhD, Chemistry, 2016, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/92994

► Membrane proteins are biologically significant targets of study due to their crucial roles in biochemical reactions, such as ion transport and cell signaling. Their study,… (more)

Subjects/Keywords: Nanodiscs; lipids; membrane; membrane protein; Cytochrome P450

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Lenov, I. L. (2016). Methodologies for the analysis of membrane systems using lipid nanodiscs. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/92994

Chicago Manual of Style (16^th Edition):

Lenov, Ivan Lenkov. “Methodologies for the analysis of membrane systems using lipid nanodiscs.” 2016. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 19, 2021. http://hdl.handle.net/2142/92994.

MLA Handbook (7^th Edition):

Lenov, Ivan Lenkov. “Methodologies for the analysis of membrane systems using lipid nanodiscs.” 2016. Web. 19 Apr 2021.

Vancouver:

Lenov IL. Methodologies for the analysis of membrane systems using lipid nanodiscs. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2016. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/2142/92994.

Council of Science Editors:

Lenov IL. Methodologies for the analysis of membrane systems using lipid nanodiscs. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2016. Available from: http://hdl.handle.net/2142/92994

University of Illinois – Urbana-Champaign

25. Frank, Daniel J. Global deconvolution of heterotropic cooperativity in cytochrome P450 3A4.

Degree: PhD, 0318, 2011, University of Illinois – Urbana-Champaign

URL: http://hdl.handle.net/2142/24520

► 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… (more)

▼ 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, called “homotropic” and “heterotropic” cooperativity respectively. Significant progress has been made towards understanding the enzyme’s complex kinetics by work in our laboratory to isolate the enzyme in Nanodiscs. This provides a homogenous, monodisperse, native-like environment, where the monomeric enzyme is biophysically characterized in the absence of detergent micellar mixtures or liposomal systems which are reported to lead to enzyme heterogeneity and obfuscate its kinetic behavior. Three distinct observable properties which CYP3A4 displays as a result of its reaction cycle are: heme iron spin state, NADPH oxidation rate, and product formation rate. Measuring these three observables as a function of substrate concentration and simultaneously fitting the data sets to a model results in a global analysis of the enzyme’s properties. It reveals the source of homotropic atypical kinetics is not due to any binding cooperativity between the substrates, but rather differences in magnitude of the functional properties from the various enzyme-substrate complexes in solution. To extend this analysis to better understand heterotropic interactions in the system, we generate an interaction surface based upon the linear combination of two substrates kinetic profiles, which corresponds to the absence of any specific heterotropic interactions between them. By comparing the observed behavior of the mixed substrate system to that of the model, we show how two commonly reported heterotropic substrates of CYP3A4 are actually not cooperative, and the observed cooperativity is due to differences in the amplitudes of the functional properties from the various binding intermediates in the system which give rise to the overall observed behavior of the enzyme. Advisors/Committee Members: Sligar, Stephen G. (advisor), Sligar, Stephen G. (Committee Chair), Gerlt, John A. (committee member), Clegg, Robert M. (committee member), Fratti, Rutilio A. (committee member).

Subjects/Keywords: cooperativity; cytochrome P450 3A4; drug-drug interactions

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Frank, D. J. (2011). Global deconvolution of heterotropic cooperativity in cytochrome P450 3A4. (Doctoral Dissertation). University of Illinois – Urbana-Champaign. Retrieved from http://hdl.handle.net/2142/24520

Chicago Manual of Style (16^th Edition):

Frank, Daniel J. “Global deconvolution of heterotropic cooperativity in cytochrome P450 3A4.” 2011. Doctoral Dissertation, University of Illinois – Urbana-Champaign. Accessed April 19, 2021. http://hdl.handle.net/2142/24520.

MLA Handbook (7^th Edition):

Frank, Daniel J. “Global deconvolution of heterotropic cooperativity in cytochrome P450 3A4.” 2011. Web. 19 Apr 2021.

Vancouver:

Frank DJ. Global deconvolution of heterotropic cooperativity in cytochrome P450 3A4. [Internet] [Doctoral dissertation]. University of Illinois – Urbana-Champaign; 2011. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/2142/24520.

Council of Science Editors:

Frank DJ. Global deconvolution of heterotropic cooperativity in cytochrome P450 3A4. [Doctoral Dissertation]. University of Illinois – Urbana-Champaign; 2011. Available from: http://hdl.handle.net/2142/24520

University of Adelaide

26. Ahirwar, Saurabh Kumar. Exploring the monooxygenase activity and selectivity of two related Cytochrome P450 enzymes.

Degree: 2020, University of Adelaide

URL: http://hdl.handle.net/2440/127956

► The cytochrome P450 enzymes CYP101B1 and CYP101C1 from Novosphingobium aromaticivorans DSM12444 are homologues of the CYP101D1 and CYP101D2 enzymes from the same bacterium and CYP101A1… (more)

▼ The cytochrome P450 enzymes CYP101B1 and CYP101C1 from Novosphingobium aromaticivorans DSM12444 are homologues of the CYP101D1 and CYP101D2 enzymes from the same bacterium and CYP101A1 (P450cam) from Pseudomonas putida. Both enzymes can efficiently hydroxylate norisoprenoids and related substrates in combination with the same ferredoxin reductase, ArR and a [2Fe-2S] ferredoxin, Arx, electron transfer partners. Even though the physiological substrates for both the enzymes are yet to be confirmed, the crystal structure of CYP101C1 bound to β -ionone and modelled structure of CYP101B1 has been generated. The Met82 residue of CYP101C1 aligns with the His85 residue of CYP101B1. In the crystallographic structure, this Met82 residue of CYP101C1, interacts with the carbonyl group of β -ionone, which makes it an interesting site for mutation as these could potentially alter the activity and hydroxylation of norisoprenoid substrates. CYP101B1 oxidised ẞ -ionone with the highest product formation rate (1010 ± 60 min-1). The CYP101C1 enzyme oxidised β -ionol with the highest product formation rate (1130 ± 30 min-1), whereas, the M82L-CYP101C1 mutant enzyme had the highest product formation rate (790 ± 22 min-1) with α-ionone. The selectivity for hydroxylation of norisoprenoids varies between CYP101B1 and CYP101C1. The M82L mutation however, did not change the selectivity for CYP101C1. For example, both β -damascone and β -ionone were hydroxylated at the C4 position by CYP101C1 and the M82L-CYP101C1 mutant. The CYP101B1 enzyme displayed an altered selectivity and hydroxylated these substrates predominantly at C3 position. When the substrate functional group was changed from a carbonyl to an alcohol (i.e. β-ionol), the hydroxylation occurred preferentially at the C3 position with all three enzymes. By comparing the oxidation of α -, β - and δ - substituted damascones, we found that the alkene moiety present inside the cyclohexyl ring did have an effect on the selectivity of oxidation. The β - substituted substrates are oxidised only at the C3 position by all three enzymes. The β - substituted substrates are oxidised at C3 position by CYP101B1 and at C4 position by CYP101C1 and M82L-CYP101C1. The δ - substituted substrate generates the 3,4-epoxide as the major product. To further explore the substrate range of CYP101B1 and CYP101C1, various substrates including cyclic ketones and cyclic esters were assessed to see if they induce enzyme activity and binding to the enzyme. The combinations of the best enzyme / substrates were then chosen to generate the oxidation metabolites in a larger quantity using whole-cell oxidation system to enable characterisation. The oxidation of 1-decalone by CYP101B1 generated a single major metabolite along with two minor products. The major product was characterized as 6-hydroxy-1-decalone and the minor product as 7-hydroxy-1-decalone. Comparison of the 1-decalone substrate to damascones, highlight the relationship of the oxidation metabolites 6-hydroxy-1-decalone to 4-hydroxy- β -damascone and… Advisors/Committee Members: Bell, Stephen G. (advisor), School of Physical Sciences (school).

Subjects/Keywords: Cytochrome P450; Enzyme; monooxygenase oxidation; CYP10181; CYP101C1

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Ahirwar, S. K. (2020). Exploring the monooxygenase activity and selectivity of two related Cytochrome P450 enzymes. (Thesis). University of Adelaide. Retrieved from http://hdl.handle.net/2440/127956

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

Ahirwar, Saurabh Kumar. “Exploring the monooxygenase activity and selectivity of two related Cytochrome P450 enzymes.” 2020. Thesis, University of Adelaide. Accessed April 19, 2021. http://hdl.handle.net/2440/127956.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

Ahirwar, Saurabh Kumar. “Exploring the monooxygenase activity and selectivity of two related Cytochrome P450 enzymes.” 2020. Web. 19 Apr 2021.

Vancouver:

Ahirwar SK. Exploring the monooxygenase activity and selectivity of two related Cytochrome P450 enzymes. [Internet] [Thesis]. University of Adelaide; 2020. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/2440/127956.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Ahirwar SK. Exploring the monooxygenase activity and selectivity of two related Cytochrome P450 enzymes. [Thesis]. University of Adelaide; 2020. Available from: http://hdl.handle.net/2440/127956

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

27. Gavira, Carole. Production de terpènes fonctionnalisés par les cytochromes P450 de plantes recombinants : Production of functionalized terpenes by recombinant plant cytochromes P450.

Degree: Docteur es, Aspects moléculaires et cellulaires de la biologie, 2013, Université de Strasbourg

URL: http://www.theses.fr/2013STRAJ009

►

Notre objectif était d’identifier des cytochromes P450 capables d’oxygéner des mono et sesquiterpènes, pour produire des molécules aux propriétés organoleptiques intéressantes labellisés « naturelles »… (more)

▼

Notre objectif était d’identifier des cytochromes P450 capables d’oxygéner des mono et sesquiterpènes, pour produire des molécules aux propriétés organoleptiques intéressantes labellisés « naturelles » par l’industrie des arômes et du parfum.Nous avons identifié 7 couples P450-substrat catalysant une conversion in vitro supérieure ≥ 45 % et/ou formant un produit attendu. Les quantités de produit obtenu par bioconversion dans la levure restent insuffisantes pour un procédé industriel. Les facteurs limitants ont été identifiés dans le cas du valencène comme : 1) la toxicité induite par les produits, 2) l’accumulation du β-nootkatol dans les membranes, 3) l’inhibition de l’enzyme par les produits réactionnels. Trois cytochromes P450 d’Arabidopsis thaliana impliqués dans le métabolisme indolique oxydent activement le limonène. Ils s’expriment dans les inflorescences et constituent le premier exemple de P450s suceptibles de participer à deux voies métaboliques indépendantes chez les plantes.

Our aim was to identify cytochromes P450 catalyzing hydroxylation of mono-and sesquiterpenes to produce functionalized "natural" compounds with interesting organoleptic properties for the flavor and fragrance industry. We identified 7 P450-substrate pairs showing . 45 % in vitro conversion and/or forming an expected product. The amounts of products resulting from yeast bioconversion were however too low for implementation of an industrial process. Factors limiting the nootkatone production from the P450-dependent bioconversion of valencene were identified : 1) toxicity for yeast of the ƒÀ-nootkatol and nootkatone products, 2) ƒÀ-nootkatol accumulation in endomembranes, 3) products inhibition of valencene hydroxylation. Three previously characterized P450s from Arabidopsis thaliana in indolic metabolism were shown to actively oxidize limonene. They are expressed in inflorescences and may provide the first demonstrated case of multifunctional P450s involved in independent plant pathways.

Advisors/Committee Members: Reichhart, Danièle (thesis director).

Subjects/Keywords: Cytochrome P450; Terpènes; Bioconversion; Arômes; Parfums; Cytochrome P450; Terpenes; Bioconversion; Scent; Aroma; 572.8

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Gavira, C. (2013). Production de terpènes fonctionnalisés par les cytochromes P450 de plantes recombinants : Production of functionalized terpenes by recombinant plant cytochromes P450. (Doctoral Dissertation). Université de Strasbourg. Retrieved from http://www.theses.fr/2013STRAJ009

Chicago Manual of Style (16^th Edition):

Gavira, Carole. “Production de terpènes fonctionnalisés par les cytochromes P450 de plantes recombinants : Production of functionalized terpenes by recombinant plant cytochromes P450.” 2013. Doctoral Dissertation, Université de Strasbourg. Accessed April 19, 2021. http://www.theses.fr/2013STRAJ009.

MLA Handbook (7^th Edition):

Gavira, Carole. “Production de terpènes fonctionnalisés par les cytochromes P450 de plantes recombinants : Production of functionalized terpenes by recombinant plant cytochromes P450.” 2013. Web. 19 Apr 2021.

Vancouver:

Gavira C. Production de terpènes fonctionnalisés par les cytochromes P450 de plantes recombinants : Production of functionalized terpenes by recombinant plant cytochromes P450. [Internet] [Doctoral dissertation]. Université de Strasbourg; 2013. [cited 2021 Apr 19]. Available from: http://www.theses.fr/2013STRAJ009.

Council of Science Editors:

Gavira C. Production de terpènes fonctionnalisés par les cytochromes P450 de plantes recombinants : Production of functionalized terpenes by recombinant plant cytochromes P450. [Doctoral Dissertation]. Université de Strasbourg; 2013. Available from: http://www.theses.fr/2013STRAJ009

INP Toulouse

28. Siddique, Muhammad Hussnain. Study of the biosynthesis pathway of the geosmin in Penicillium expansum : Etude de la voie de biosynthèse de la geosmine chez Penicillium expansum.

Degree: Docteur es, Ingénieries microbiennes et enzymatique, 2012, INP Toulouse

URL: http://www.theses.fr/2012INPT0085

►

La géosmine est un terpénoïde, provoquant un goût moisi-terreux associée à des flaveurs atypiques dans l'eau et le vin. Chez les bactéries, la voie de… (more)

▼

La géosmine est un terpénoïde, provoquant un goût moisi-terreux associée à des flaveurs atypiques dans l'eau et le vin. Chez les bactéries, la voie de biosynthèse de la géosmine est bien caractérisée, mais peu de connaissance sont disponibles au sujet de sa biosynthèse chez les eucaryotes, en particulier dans les champignons filamenteux. L'origine de la géosmine dans la vigne est en grande partie attribuable à la présence de Penicillium expansum sur les raisins. Dans cette thèse, afin de mieux comprendre la voie de biosynthèse de la géosmine chez Penicillium expansum, nous avons décrit la caractérisation et l'analyse de "gpe1", un gène codant pour une cytochrome P450 monooxygénase impliquée dans la biosynthèse de la géosmine. Nous avons démontré que les deux fragments d'ADN: p450-1 et p450-2 appartiennent à un seul gène du cytochrome p450 (gpe1). La séquence d'acides aminés déduite de gpe1 a une identité moyenne de 40 % avec les enzymes PbP450-2 et P450-4 qui ont été trouvées impliquées respectivement dans la synthèse d'indole diterpène et dans la synthèse des gibbérellines. Les amplifications par PCR effectuée sur quatorze espèces de Penicillium ont montré que seules les espèces producteurices de la géosmine ont donné le même fragment de ~1,2 kb que gpe1. L'analyse du gène gpe1 nous a permis d'identifier la présence de certains domaines conservés de cytochromes P450 monooxygénases. Ensuite, la caractérisation fonctionnelle du gène gpe1 chez P. expansum M2230 a été décrite. Nous avons montré que les mutants de gpe1 ont perdus leur pouvoir de produire la géosmine alors que les révertants de gpe1 ont rétablis leur pouvoir de production. Enfin, nous avons démontré qu'une polykétide synthase putative et une putative NRPS sont présentes sur le côté droit du gène gpe1 proposant que le gène gpe1 pourrait être une partie d'un «Cluster» codant pour la biosynthèse de métabolites secondaires.

Geosmin is a terpenoid, an earthy-musty compound associated with off-flavors in water and wine. In bacteria, the biosynthesis pathway of geosmin is well characterized, but little is known about its biosynthesis in eukaryotes, especially in filamentous fungi. The origin of geosmin in grapevine is largely attributable to the presence of Penicillium expansum on grapes. In this thesis, we have described the characterization and analysis of "gpe1", a gene encoding a cytochrome P450 monooxygenase probably involved in the biosynthesis of geosmin in P. expansum M2230, in order to better understand of the biosynthesis pathway of geosmin in this species. We demonstrated that the two DNA fragments i.e. p450-1 and p450-2 belong to a single cytochrome p450 gene (gpe1). We showed that the deduced amino acid sequence of gpe1 has an average identity of 40 % with PbP450-2 and P450-4 enzymes which have been found involved in indole diterpene synthesis and in gibberellin synthesis respectively. Then, the results of PCRs performed on the fourteen Penicillium species showed that only Penicillium species which were producers of geosmin gave the same fragment…

Advisors/Committee Members: Lebrihi, Ahmed (thesis director), Liboz, Thierry (thesis director).

Subjects/Keywords: Cytochrome P450 monooxygénase; Géosmine; Gpe1; Penicillium expansum; Cytochrome P450 monooxygenase; Geosmin; Gpe1; Penicillium expansum

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Siddique, M. H. (2012). Study of the biosynthesis pathway of the geosmin in Penicillium expansum : Etude de la voie de biosynthèse de la geosmine chez Penicillium expansum. (Doctoral Dissertation). INP Toulouse. Retrieved from http://www.theses.fr/2012INPT0085

Chicago Manual of Style (16^th Edition):

Siddique, Muhammad Hussnain. “Study of the biosynthesis pathway of the geosmin in Penicillium expansum : Etude de la voie de biosynthèse de la geosmine chez Penicillium expansum.” 2012. Doctoral Dissertation, INP Toulouse. Accessed April 19, 2021. http://www.theses.fr/2012INPT0085.

MLA Handbook (7^th Edition):

Siddique, Muhammad Hussnain. “Study of the biosynthesis pathway of the geosmin in Penicillium expansum : Etude de la voie de biosynthèse de la geosmine chez Penicillium expansum.” 2012. Web. 19 Apr 2021.

Vancouver:

Siddique MH. Study of the biosynthesis pathway of the geosmin in Penicillium expansum : Etude de la voie de biosynthèse de la geosmine chez Penicillium expansum. [Internet] [Doctoral dissertation]. INP Toulouse; 2012. [cited 2021 Apr 19]. Available from: http://www.theses.fr/2012INPT0085.

Council of Science Editors:

Siddique MH. Study of the biosynthesis pathway of the geosmin in Penicillium expansum : Etude de la voie de biosynthèse de la geosmine chez Penicillium expansum. [Doctoral Dissertation]. INP Toulouse; 2012. Available from: http://www.theses.fr/2012INPT0085

Université de Lorraine

29. Shahabi, Payman. Cytochrome P450 et inflammation : approche pharmacogénomique et aspects moleculaires des effets anti-inflammatoires des thiénopyridines : Cytochrome P450 and inflammation : pharmacogenomic approach and molecular aspects of anti-inflammatory effects of theinopyridines.

Degree: Docteur es, Sciences de la vie et de la santé, 2013, Université de Lorraine

URL: http://www.theses.fr/2013LORR0320

►

Cette thèse est dédiée à l'approche pharmacogénétique des effets anti-inflammatoires de la thérapie par les thiénopyridines. Prenant en compte que les plaquettes activées jouent un… (more)

▼

Cette thèse est dédiée à l'approche pharmacogénétique des effets anti-inflammatoires de la thérapie par les thiénopyridines. Prenant en compte que les plaquettes activées jouent un rôle central dans les états inflammatoires et que des polymorphismes du cytochrome P450 (CYP) 2C19 ont été montré responsable de différences inter individuelle dans la réponse de l'effet antiplaquettaire de thiénopyridines, nous avons émis l'hypothèse que CYP2C19 *2 ou *17 sont également associés à la variabilité interindividuelle du potentiel antiinflammatoire des thiénopyridines. Les marqueurs d'inflammation utilisés pour suivre l'effet des thiénopyridines sont : la CRP, l'haptoglobines et l'orosomucoïde. Nous avons démontré que pour interpréter les valeurs de l'haptoglobine il était nécessaire de tenir compte du statut génétique et obtenir des valeurs de référence stratifiés. D'abord dans une population saine, nous n'avons pas trouvé d'association entre les valeurs de base des marqueurs inflammatoires et les polymorphismes fréquents de CYP époxygenases. Dans une population après intervention coronarienne percutanée qui était composée de 1128 sujets traités par clopidogrel ou prasugrel, le niveau de CRP observé a montré une interaction significative entre le tabac et le polymorphisme de CYP 2C19 ; cet effet est indépendant du niveau d'agrégation plaquettaire. Dans une 3ème population, sur plus de 1000 sujets hospitalisés à Coimbra, nous avons identifié une interaction entre le clopidogrel CYP2C19 et les médicaments bloqueurs des canaux calciques. En résumé, tous ces résultats obtenus sur plusieurs populations laissent envisager que les marqueurs d'inflammation pourraient être un moyen intéressant de suivi des patients lors de la thérapeutique par les thiénopyridines

The main part of the thesis is devoted to pharmacogenetic approach to the anti-inflammatory effects of thienopyridine therapy. Taking into the account that activated platelets play a central role in the inflammatory responses and that CYP2C19 gain- and loss-of-function polymorphisms (*2 and *17) are sources of inter-individual difference in response to the anti-platelet effects of thienopyridines, we hypothesized that *2 and/or *17 alleles are also associated with inter-individual variability in the potential inflammation-reducing effects of thienopyridines. The following markers were used to test the hypothesis: CRP, haptoglobin and orosomucoid acid. To be reliably interpretable in daily medical practice, genetic status should be considered for partitioning the reference values of haptoglobin. In a small healthy population, no significant association was observed between *2 allele and changes in levels of inflammatory markers from baseline to 7 days after administration of clopidogrel and our findings did not support the notion that the genetic variations of CYP epoxygenases are associated with the level of inflammatory markers. Also, in post-PCI population consisting of 1128 on-clopidogrel or on-prasugrel patients, CRP levels were observed to be regulated with a…

Advisors/Committee Members: Visvikis-Siest, Sophie (thesis director), Siest, Gérard (thesis director).

Subjects/Keywords: Thiénopyridines; Clopidogrel; Prasugrel; Cytochrome P450; Époxygenases; Inflammation; Thienopyridines; Clopidogrel; Prasugrel; Cytochrome P450; Epoxygenases; Inflammation; 615.1

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

Shahabi, P. (2013). Cytochrome P450 et inflammation : approche pharmacogénomique et aspects moleculaires des effets anti-inflammatoires des thiénopyridines : Cytochrome P450 and inflammation : pharmacogenomic approach and molecular aspects of anti-inflammatory effects of theinopyridines. (Doctoral Dissertation). Université de Lorraine. Retrieved from http://www.theses.fr/2013LORR0320

Chicago Manual of Style (16^th Edition):

Shahabi, Payman. “Cytochrome P450 et inflammation : approche pharmacogénomique et aspects moleculaires des effets anti-inflammatoires des thiénopyridines : Cytochrome P450 and inflammation : pharmacogenomic approach and molecular aspects of anti-inflammatory effects of theinopyridines.” 2013. Doctoral Dissertation, Université de Lorraine. Accessed April 19, 2021. http://www.theses.fr/2013LORR0320.

MLA Handbook (7^th Edition):

Shahabi, Payman. “Cytochrome P450 et inflammation : approche pharmacogénomique et aspects moleculaires des effets anti-inflammatoires des thiénopyridines : Cytochrome P450 and inflammation : pharmacogenomic approach and molecular aspects of anti-inflammatory effects of theinopyridines.” 2013. Web. 19 Apr 2021.

Vancouver:

Shahabi P. Cytochrome P450 et inflammation : approche pharmacogénomique et aspects moleculaires des effets anti-inflammatoires des thiénopyridines : Cytochrome P450 and inflammation : pharmacogenomic approach and molecular aspects of anti-inflammatory effects of theinopyridines. [Internet] [Doctoral dissertation]. Université de Lorraine; 2013. [cited 2021 Apr 19]. Available from: http://www.theses.fr/2013LORR0320.

Council of Science Editors:

Shahabi P. Cytochrome P450 et inflammation : approche pharmacogénomique et aspects moleculaires des effets anti-inflammatoires des thiénopyridines : Cytochrome P450 and inflammation : pharmacogenomic approach and molecular aspects of anti-inflammatory effects of theinopyridines. [Doctoral Dissertation]. Université de Lorraine; 2013. Available from: http://www.theses.fr/2013LORR0320

30. MacLean, Marina A. Exploring Insect Enzymes as Catalyst for Bioconversion of Value Added Products.

Degree: 2012, University of Nevada – Reno

URL: http://hdl.handle.net/11714/3752

► Demand for fine chemicals and value-added products has increased annually concomitantly with the rapid expansion of biocatalytic production of these chemicals. With an increased mandate… (more)

▼ Demand for fine chemicals and value-added products has increased annually concomitantly with the rapid expansion of biocatalytic production of these chemicals. With an increased mandate for chemicals in the pharmaceutical, agricultural, scents and flavorants industry, it is essential to identify enzymes capable of performing specific, complex chemical reactions in an efficient, economical and environmentally friendly manner. Insects produce secondary metabolites that are potential value-added chemicals, therefore insect enzymes provide a rich source of catalysts that can be added to the collection of biocatalysts used to perform these intricate tasks. This thesis explores the biochemical role of three insect enzymes, CYP9T3, MPB-CPR, and CG4020, which are involved in lipid metabolism and could potentially be used as biocatalysts for value-added products. All three enzymes were expressed with a baculoviral system in Sf9 cells and used in functional assays. Eastern Ips pini CYP9T3 is a cytochrome P450 with 94% sequence identity to western Ips pini CYP9T2. CYP9T3 accepts myrcene, (+)- and (-)-α-pinene, (+)- and (-)- limonene, and (+)-3-carene as substrates, a pattern similar to CYP9T2. However, the enantiomeric ratio of (4R)-(-)-ipsdienol to (4S)-(+)-ipsdienol is significantly different between CYP9T3 and CYP9T2. Additionally, the product from (-)-α-pinene is transverbenol with CYP9T3 and myrtenol with CYP9T2. Assays with β-pinene, terpinolene, γ-terpinene, α-phellandrene did not yield detectable products by either CYP9T3 or CYP9T2. Cytochromes P450 require the transfer of electrons from a protein partner, commonly cytochrome P450 reductases. Mountain pine beetle cytochrome P450 ii reductase (MPB-CPR) is the first bark beetle cytochrome P450 reductase to be isolated and characterized. MPB-CPR is 69% identical to house fly-CPR (HF-CPR), the reductase used in previous bark beetle P450 functional assays. Recombinant MPB-CPR microsomes reduce cytochrome c with apparent Km and vmax of 85.04 µM and 8.42 nmol·min-1·µg total protein-1, respectively. Initial kinetic assays with CYP9T3 indicate that MPB-CPR reduces the P450 in the presence of myrcene with apparent Km and vmax values of 15.8 uM and 11.3 nmol·min-1·U enzyme-1, respectively. The final step in hydrocarbon biosynthesis in insects is the removal of one carbon from a fatty aldehyde through the action of an oxidative decarbonylase, CYP4G2. Experimental evidence from M. domestica microsomal preparations indicates that a fatty acyl-CoA is reduced to a fatty aldehyde prior to the oxidative decarbonylation reaction and the candidate enzyme is a fatty acyl-CoA reductase (FAR). CG4020, a Drosophila melanogaster FAR, has an expression pattern similar to CYP4G1, the D. melanogaster homologue of CYP4G2. Additionally, suppression of CG4020 produces flies with fifty percent less total hydrocarbon than wild type flies. Preliminary assays with expressed CG4020 did not confirm the biochemical function of this enzyme, however they did provide… Advisors/Committee Members: Tittiger, Claus R. (advisor), Blomquist, Gary J. (committee member), Forister, Matthew (committee member).

Subjects/Keywords: bark beetle; cytochrome P450; cytochrome P450 reductase; fatty acyl-CoA reductase; ipsdienol; lipid metabolism

Record Details Similar Records Cite « Share

❌

APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6^th Edition):

MacLean, M. A. (2012). Exploring Insect Enzymes as Catalyst for Bioconversion of Value Added Products. (Thesis). University of Nevada – Reno. Retrieved from http://hdl.handle.net/11714/3752

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16^th Edition):

MacLean, Marina A. “Exploring Insect Enzymes as Catalyst for Bioconversion of Value Added Products.” 2012. Thesis, University of Nevada – Reno. Accessed April 19, 2021. http://hdl.handle.net/11714/3752.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7^th Edition):

MacLean, Marina A. “Exploring Insect Enzymes as Catalyst for Bioconversion of Value Added Products.” 2012. Web. 19 Apr 2021.

Vancouver:

MacLean MA. Exploring Insect Enzymes as Catalyst for Bioconversion of Value Added Products. [Internet] [Thesis]. University of Nevada – Reno; 2012. [cited 2021 Apr 19]. Available from: http://hdl.handle.net/11714/3752.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

MacLean MA. Exploring Insect Enzymes as Catalyst for Bioconversion of Value Added Products. [Thesis]. University of Nevada – Reno; 2012. Available from: http://hdl.handle.net/11714/3752

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Open Access Theses and Dissertations