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The Role of Membrane Bound Enzymes in Metabolism of Xenobiotics in Human
Skarka, Adam ; Wsól, Vladimír (advisor) ; Bílková, Zuzana (referee) ; Hodek, Petr (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate Mgr. Adam Skarka Supervisor Prof. Ing. Vladimír Wsól, Ph.D. Title of Doctoral Thesis The role of membrane bound enzymes in metabolism of xenobiotics in human Heterogeneous substances named xenobiotics are commonly present in wide surroundings of man. Some of them are actively or passively acquired into organism and undergo metabolic transformation, which lead to their excretion. In this case, important role is played by different enzymatic systems. The most known system is superfamily of cytochrome P450s catalyzing oxidation reactions. However, the importance of reducing systems like superfamilies of short chain dehydrogenases/reductases (SDR), middle chain dehydrogenases/reductases (MDR) and aldo keto reductases (AKR) have grown recently. Carbonyl group, the target of reduction catalyzed by SDR, MDR and AKR superfamilies, is also present in various groups of drugs, e.g. antineoplastics and non-steroidal anti-inflammatory drugs. Conversion of this group can lead to the loss of therapeutic effect and/or to the increase of toxicity for organism. Some xenobiotics contain so called prochiral functional group in their structure, e.g. carbonyl group. Conversion of this group can lead to the...
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Numerické řešení inverzních integrálních rovnic matematického modelování ve výzkumu biopaliv
Bílková, Zuzana ; Hnětynková, Iveta (advisor) ; Kofroň, Josef (referee)
Název práce: Numerické řešení inverzních integrálních rovnic matema- tického modelování ve výzkumu biopaliv Autor: Zuzana Bílková Katedra / Ústav: Katedra numerické matematiky Vedoucí bakalářské práce: RNDr. Iveta Hnětynková, Ph.D., Katedra nu- merické matematiky MFF UK Abstrakt: Cílem této bakalářské práce je numerické řešení Fredholmových integrálních rovnic prvního řádu, které se vyskytují ve výzkumu biopaliv. Práce se zaměřuje na studium Lagrangových interpolačních kvadraturních formulí. Uvažujeme lichoběžníkové a Simpsonovo pravidlo s využitím ekvidistantního a logaritmického dělení. Cílem práce je srovnání těchto pravidel a nalezení nej- vhodnější metody. Práce se dále zabývá určením minimálního počtu naměře- ných dat tak, abychom dosáhli dané přesnosti. Poznatky jsou demonstrovány na numerických experimentech se simulovanými daty. Klíčová slova: inverzní integrální rovnice, kvadratura, konvergence, odhad chyby 1
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Optimization of purification of human membrane-bound carbonyl reductase.
Andrýs, Rudolf ; Wsól, Vladimír (advisor) ; Bílková, Zuzana (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate: Rudolf Andrýs Supervisor: prof. Ing. Vladimír Wsól, Ph.D Title of diploma thesis: Optimalization of purification of a human membrane-bound carbonyl reductase Carbonyl reductases are enzymes participating in metabolic pathways of various eobiotics and xenobiotics. Of all known enzymes metabolizing xenobiotics only 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) is found in the microsomal membrane. It also contributes to metabolism of prochiral anticancer drug oracin, which main metabolic pathway is a carbonyl reduction on the position 11 leading to two enantiomers of (+) an (-) 11-dihydrooracin (DHO). Based on the discrepancy between microsomes and 11β-HSD1 stereospecifity of oracin reduction exist a hypothesis of participation an unknown microsomal enzyme in oracin metabolism. The aim of this study is to purify a new microsomal carbonyl reducing enzyme contributing in the biotransformation of oracin. Human liver microsomes were solubilised and desalted. The prepared sample was used for the first purification step on Q-Sepharose. Captured flow through fraction Q2 was loaded on Phenyl-sepharose. Captured suitable fraction P11 was used for third purification step by gel filtration. All...
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Posttranslational modification of proteins - their analysis and physiological aspects
Mikulíková, Kateřina ; Mikšík, Ivan (advisor) ; Bílková, Zuzana (referee) ; Glatz, Zdeněk (referee)
This thesi s is eoneerned with the deteetion of posttranslational modifieation of proteins. These proteins are identified using liquid ehromatography and eapillary eleetrophoresis, their eoupling and eoupling to mass speetrometry. The first part of the theoretieal ehapter is devoted to the strueture, classifieation and metabolits ehanges of proteins in the human body. Major attention is foeused on eollagen, its strueture and individual eollagen types. The seeond part eonsiders the problems of nonenzymatie glyeation and its influenee on the body and engage in produets of posttranslational modifieation. The third part summarizes the individual separation proeedures and analysis of posttranslationaly modified proteins. The seeond ehapter deseribes experimental parameters, including ehemieals, instrumentation, materials and methods. The preparation of individual samples is also deseribed. All results and findings are summarized and diseussed in the last ehapter. This ehapter is divided in two parts. The first part foeuses on problems of in vivo experiments. The seeond part foeuses on problems of in vitro experiments. Powered by TCPDF (www.tcpdf.org)
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The Role of Reductases in Cancer.
Škarydová, Lucie ; Wsól, Vladimír (advisor) ; Hodek, Petr (referee) ; Bílková, Zuzana (referee)
Only a small attention was paid for long time to reducing enzymes, but today it is clear that these are an important part of the endogenous metabolism and also the phase I biotransformation of xenobiotics. The significant group of reducing enzymes are carbonyl reductases that belong to two superfamilies - short chain dehydrogenases/reductases (SDR) and aldo-keto reductases (AKR). Their role in cancer is now intensively studied and their functions in cancer it is possible to divide into two main sections. It is known that carbonyl reductases play a substantial role in hormone-dependent cancers as prostate, breast or endometrial cancer. Active estrogens or androgens are important growth factors for these cancers because they evoke increasing of cell proliferation so that elevated possibility of mutations of important genes and development of cancer. Carbonyl reductases along with other enzymes (e.g. aromatase) participate in formation of these active sex hormones in extragonadal tissues, so an inhibition of such enzymes may be a target of anticancer therapy of hormone-dependent cancers. It is necessary to determine which enzymes are essential for the formation of active sex hormones in particular types of cancers. Besides hormone-dependent cancers, carbonyl reductases play also role in cancers that...
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