Дисертації з теми "Metabolism of cholesterol derivatives"
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Norlin, Maria. "Cytochrome P450 Enzymes in the Metabolism of Cholesterol and Cholesterol Derivatives." Doctoral thesis, Uppsala University, Department of Pharmaceutical Biosciences, 2000. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1086.
Cholesterol is metabolized to a variety of important biological products in the body including bile acids and vitamin D. The present investigation is focused on enzymes that catalyze 7α-hydroxylation or 27-hydroxylation in the metabolism of cholesterol, oxysterols (side chain-hydroxylated derivatives of cholesterol) and vitamin D3. The enzymes studied belong to the cytochrome P450 enzyme families CYP7 and CYP27.
The study describes purification of a cytochrome P450 enzyme fraction active in 7α-hydroxylation of 25-hydroxycholesterol, 27-hydroxycholesterol, dehydroepiandrosterone and pregnenolone from pig liver microsomes. Peptide sequence analysis indicated that this enzyme fraction contains an enzyme belonging to the CYP7B subfamily. The purified enzyme was not active towards cholesterol or testosterone. Purification and inhibition experiments suggested that hepatic microsomal 7α -hydroxylation of 27-hydroxycholesterol and dehydroepiandrosterone involves at least two enzymes, probably closely related.
The study shows that recombinantly expressed human and rat cholesterol 7α -hydroxylase (CYP7A) and partially purified pig liver cholesterol 7α -hydroxylase are active towards 20(S)-, 24-, 25- and 27-hydroxycholesterol. CYP7A was previously considered specific for cholesterol and cholestanol. The 7α -hydroxylation of 20(S)-, 25-, and 27-hydroxycholesterol in rat liver was significantly increased by treatment with cholestyramine, an inducer of CYP7A. Cytochrome P450 of renal origin showed 7α -hydroxylase activity towards 25- and 27-hydroxycholesterol, dehydroepiaundrosterone and pregnenolone but not towards 20(S)-, 24-hydroxycholesterol or cholesterol. The results indicate a physiological role for CYP7A as an oxysterol 7α -hydroxylase, in addition to the previously known human oxysterol 7α -hydroxylase CYP7B.
The role of renal sterol 27-hydroxylase (CYP27A) in the bioactivation of vitamin D3 was studied with cytochrome P450 fractions purified from pig kidney mitochondria. Purification and inhibition experiments and experiments with a monoclonal antibody against CYP27A indicated that CYP27A plays a role in renal 25-hydroxyvitamin D3 l α -hydroxylation.
The expression of CYP7A, CYP7B and CYP27A during development was studied. The levels of CYP27A in livers of newborn and six months old pigs were similar whereas the levels of CYP7A increased. The expression of CYP7B varied depending on the tissue. The expression of CYP7B increased with age in the liver whereas the CYP7B levels in kidney showed a marked age-dependent decrease.
Patel, Dilipkumar. "Cholesterol metabolism in monocyte-derived macrophages." Thesis, Imperial College London, 1990. http://hdl.handle.net/10044/1/46492.
Hoang, Van Quyen. "Cholesterol metabolism in cultured hamster hepatocytes." Thesis, Royal Veterinary College (University of London), 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.522583.
曾紹怡 and Siu-yee Patricia Tsang. "Regulation of cholesterol metabolism in hepatocytes." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31969835.
Simonen, Piia. "Cholesterol metabolism in type 2 diabetes." Helsinki : University of Helsinki, 2002. http://ethesis.helsinki.fi/julkaisut/laa/kliin/vk/simonen/.
Tsang, Siu-yee Patricia. "Regulation of cholesterol metabolism in hepatocytes." Hong Kong : University of Hong Kong, 2000. http://sunzi.lib.hku.hk/hkuto/record.jsp?B22032459.
Boone, Lindsey R. "Thyroid Hormone Regulation of Cholesterol Metabolism." [Tampa, Fla] : University of South Florida, 2009. http://purl.fcla.edu/usf/dc/et/SFE0003089.
Sampson, William James. "The intracellular control of cholesterol metabolism." Thesis, University of Edinburgh, 1988. http://hdl.handle.net/1842/26913.
Jiang, Zhao-Yan. "Studies on cholesterol and bile acid metabolism in Chinese cholesterol gallstone patients." Stockholm, 2010. http://diss.kib.ki.se/2010/978-91-7409-844-0/.
Skogsberg, Josefin. "PPAR delta : its role in cholesterol metabolism /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-604-9.
Alrokayan, Salman A. H. "Molecular biology of cholesterol metabolism in humans." Thesis, University of Nottingham, 1995. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.261424.
Al-Khfajy, Wrood Salim Dawood. "Role Of Transmembrane 141 in Cholesterol Metabolism." Kent State University / OhioLINK, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=kent1416142859.
Bayley, Timothy M. "The longer term effect of early dietary cholesterol on cholesterol metabolism in infants /." Thesis, McGill University, 1998. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=37522.
Bayley, Timothy M. "The longer term effect of early dietary cholesterol on cholesterol metabolism in infants." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0016/MQ44125.pdf.
Mortaz, Maryam. "Effect of early factors on later cholesterol metabolism." Thesis, King's College London (University of London), 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.394365.
Manson, Mary Elizabeth. "Mechanisms of Altered Cholesterol Metabolism in Cystic Fibrosis." Case Western Reserve University School of Graduate Studies / OhioLINK, 2011. http://rave.ohiolink.edu/etdc/view?acc_num=case1296137626.
Vidimce, Josif. "Impact of Hyperbilirubinaemia on Cholesterol Metabolism and Bioenergetics." Thesis, Griffith University, 2020. http://hdl.handle.net/10072/394687.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
Full Text
Alasmi, Mahmood Mohamed. "EFFECTS OF CHOLESTEROL SUPPLEMENTATION ON CHOLESTEROL SYNTHESIS RATES IN INFANTS." University of Cincinnati / OhioLINK, 2000. http://rave.ohiolink.edu/etdc/view?acc_num=ucin974741712.
Kacher, Radhia. "Role of the cholesterol hydroxylase enzyme CYP46A1 in cholesterol metabolism and neuroprotection in Huntington's disease." Thesis, Sorbonne université, 2019. http://www.theses.fr/2019SORUS154.
Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by abnormal CAG expansion on huntingtin’s gene. Recently, altered brain cholesterol homeostasis has been implicated in HD. Particularly, the expression of CYP46A1, the rate-limiting enzyme for cholesterol degradation in the brain, is decreased in patients’ putamen and in the striatum of HD mouse models. We restored CYP46A1 expression into the striatum of the zQ175 mice. Behavioral, neuropathological and molecular tests were performed and showed an improvement of locomotor activity and histological landmarks. Cholesterol homeostasis was restored with an increase of cholesterol degradation and synthesis. CYP46A1 induced a new transcriptional signature, with restoration of pathways involved in autophagy, proteasome, synaptic communication and axonal transport, which are known to be dysfunctional in HD. CYP46A1 improved synaptic transmission and spine density in the striatum of the zQ175 mice. Aggregate clearance mediated by autophagy and proteasome was increased after CYP46A1 expression. Finally, BDNF and TrkB transport were enhanced by CY46A1 in HD in vitro models. Overall, CYP46A1 restoration alleviates the zQ175 pathological phenotype through a global compensation. To gain further insights into CYP46A1 neuroprotection, a cell sorting strategy was set up to study the transcriptomic and lipidomic signature in purified neurons and astrocytes. This method will lead to a greater understanding of cell-type-specific regulations and cell communication. Altogether, this project gave new insights into the potential application of CYP46A1 restoration as a therapeutic strategy in HD
Babiker, Amir H. M. "Studies on a novel oxidative mechanism for elimination of extrahepatic cellular cholesterol /." Stockholm, 1998. http://diss.kib.ki.se/1998/91-628-3308-1/.
Parini, Paolo. "Hormonal regulation of hepatic cholesterol and lipoprotein metabolism : effects of estrogen and growth hormone /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3372-3/.
Descat, Amandine. "Développements de méthodes d'analyse des plastifiants de type phtalates et des acides biliaires dans des matrices biologiques : applications dans différents contextes physiopathologiques." Electronic Thesis or Diss., Université de Lille (2022-....), 2023. http://www.theses.fr/2023ULILS054.
This thesis has two main focuses:1/ Plasticizers, including phthalates, have been identified as category 1b carcinogenic, mutagenic and reprotoxic (CMR) and as endocrine disruptors. Di-2-ethylhexyl phthalate (DEHP) is one of the most common plasticizers and is generally associated with polyvinyl chloride (PVC) in medical devices. As DEHP is not covalently bound to PVC, it can easily migrate into lipophilic matrices and then reach the bloodstream. It is metabolized by the liver into mono-2-ethylhexyl phthalate (MEHP), which is just as toxic. In recent years, alternative plasticizers to DEHP have been developed, notably di-2-ethylhexyl terephthalate (DEHT), which is metabolized in vivo to mono-2-ethylhexyl terephthalate (MEHT).The first part of this thesis involved developing methods for measuring plasticizers and their metabolites in various biological matrices, such as plasma. Two LC-MS/MS methods were developed for the determination of DEHP and MEHP as well as DEHT metabolites. As the ionization in mass spectrometry of DEHT is very low, a LC-UV method was developed to quantify this terephthalate. These methods have made it possible to estimate the release of DEHP and DEHT from blood bags and to measure their primary metabolites in blood products.2/ Bile acids (BA) are a large family of steroids made up of numerous species. They are synthesized in the liver and intestine and represent the main route of cholesterol catabolism. 7a-hydroxy-4-cholesten-3-one (C4) is the precursor of BA. BA play an essential role in lipid absorption but also in cell signaling, as they are ligands for the nuclear receptor 'Farnesoid X receptor' (FXR) and/or the G protein-coupled membrane receptor, TGR5. These receptors, and hence their ligands, are involved in glucose homeostasis, lipid homeostasis and energy expenditure. Any modulation of the BA profile can therefore lead to changes in metabolic homeostasis. The second part of this thesis involved developing two LC-MS/MS assay methods for 31 BA species and C4 in different biological matrices, including plasma. A specific method for the determination of recently described BA derived from LCA in caecal contents is currently being optimized. These methods have made it possible to analyze variations in the BA profile in various cardiometabolic disease contexts (obesity, insulin resistance, type 2 diabetes, NAFLD).In conclusion, the analytical methods developed for quantifying plasticizers and BA have been validated and applied in preclinical and clinical studies. Interestingly, data from the literature and preliminary transient transfection assays have shown that phthalates and their metabolites modulate the activity of the peroxisome proliferator-activated receptor alpha (PPARa), a key regulator of metabolic homeostasis and expression of CYP7A1 (a major enzyme in hepatic BA synthesis). The analytical tools developed in this thesis open up original perspectives for studying the effects of phthalates on metabolic homeostasis via the regulation of BA metabolism. All of this work has made it possible to link analytical developments and applications in the field of biology and health
Stamler, Christopher John. "The effects of lipoprotein surface charge on cholesterol metabolism." Thesis, University of Ottawa (Canada), 2002. http://hdl.handle.net/10393/6139.
Heverin, Maura. "Brain cholesterol metabolism : a study of mouse and man /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-474-0/.
Lack, Nathan. "Characterization of an operon involved in mycobacterial cholesterol metabolism." Thesis, University of Oxford, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.509971.
Lütjohann, Dieter. "Cholesterol homeostasis in the brain : importance of 24S-hydroxylation /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3410-X/.
Othman, Rgia Ali. "Assessment of sterol metabolism in sitosterolemia." Taylor & Francis, 2012. http://hdl.handle.net/1993/24317.
February 2015
Zhou, Huali, and 周華麗. "Reverse cholesterol transport in type 2 diabetes mellitus." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B39794003.
Rees, Stephen Edward. "Causal probabilistic network modelling of lipid and lipoprotein metabolism." Thesis, City University London, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.241469.
Ntanios, Fady Y. "Cholesterol lowering efficacy of plant sterols : mechanisms of action." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk1/tape11/PQDD_0018/NQ44534.pdf.
O'Kane, Maurice J. "The assay, structure and metabolism of pre-beta high density lipoprotein." Thesis, Queen's University Belfast, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.282043.
Matasconi, Manuela. "Pituitary regulation of plasma lipoprotein metabolism and intestinal cholesterol absorption /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-571-2/.
Bhattacharya, Bonhi Shikha. "Mathematical modelling of low density lipoprotein metabolism intracellular cholesterol regulation." Thesis, University of Reading, 2011. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.542271.
McAstocker, Michael. "The effects of dietary dairy products on mammalian cholesterol metabolism." Thesis, Queen's University Belfast, 1992. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.317559.
Wright, Sarah M. "The effects of dietary proteins on cholesterol and lipoprotein metabolism." Thesis, University of Nottingham, 1994. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.262479.
Berghoff, Stefan [Verfasser]. "Cholesterol metabolism in mouse models of Multiple Sclerosis / Stefan Berghoff." Göttingen : Niedersächsische Staats- und Universitätsbibliothek Göttingen, 2020. http://d-nb.info/122317154X/34.
Landry, Chandra. "Phosphatidylcholine Metabolism and ACAT Affect the Trafficking of LDL-derived Free Cholesterol in Cholesterol-loaded CHO Cells." Thèse, Université d'Ottawa / University of Ottawa, 2012. http://hdl.handle.net/10393/23087.
Brassil, Patrick John. "Cytochrome P450 cholesterol 7#alpha#-hydroxylase : a study of its role and modulation in hepatic cholesterol metabolism." Thesis, Imperial College London, 1996. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.244184.
Howell, Tanya J. "Effects of natural and synthetic phytosterol administration on cholesterol metabolism in normolipidemic humans." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq29716.pdf.
Tatidis, Loukas. "Cholesterol turnover in acute myelogenous leukemia with special emphasis on regulation of low density lipoprotein receptor expression in leukemic cells /." Stockholm : [Karolinska Univ. Press], 2001. http://diss.kib.ki.se/2001/91-7349-054-7/.
Gibson, A. W. "The role of the reticuloendothelial system in LDL metabolism." Thesis, University of Glasgow, 1985. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.381452.
Devlin, Angela Marie. "The effect of early diet on hepatic cholesterol metabolism in piglets." Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1998. http://www.collectionscanada.ca/obj/s4/f2/dsk2/tape17/PQDD_0010/NQ34518.pdf.
Lin, Emme Chee-Kwun. "Interactive effects of dietary fat type and cholesterol quantity on cholesterol and lipoprotein metabolism in the guinea pig." Diss., The University of Arizona, 1994. http://hdl.handle.net/10150/187525.
Gälman, Cecilia. "Modulation of bile acid and cholesterol metabolism in health and disease /." Stockholm ; Karolinska institutet, 2004. http://diss.kib.ki.se/2004/91-7349-948-x.
Mann, Karen M. "The impact of apolipoprotein E on cholesterol metabolism and Alzheimer's disease." Connect to text online, 2005. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=case1121354439.
Plat, Jogchum. "Plant stanol esters effects on cardiovascular risk markers and cholesterol metabolism /." Maastricht : Maastricht : Universiteit Maastricht ; University Library, Maastricht University [Host], 2001. http://arno.unimaas.nl/show.cgi?fid=7047.
Li, Tiangang. "PREGNANE X RECEPTOR REGULATION OF BILE ACID METABOLISM AND CHOLESTEROL HOMEOSTASIS." Kent State University / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=kent1132160196.
Gullberg, Hjalmar. "Thyroid hormone receptors in liver metabolism /." Stockholm, 2002. http://diss.kib.ki.se/2002/91-7349-190-x/.
Winzerling, Joy Johnson. "Human peritoneal cells--a potential model for the study of cholesterol metabolism in macrophages." Diss., The University of Arizona, 1990. http://hdl.handle.net/10150/185211.
Li, Yan. "Genetic analysis of Alzheimer's disease associated genes : a perspective from abnormal cholesterol metabolism /." View the Table of Contents & Abstract, 2008. http://sunzi.lib.hku.hk/hkuto/record/B39711663.