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The effect of iron on the metabolism of the protozoan Trypanosoma brucei
Arbon, Dominik ; Konvalinka, Jan (advisor) ; Grantz Šašková, Klára (referee)
Iron ions are essential components of numerous cell processes. Their utilisation is strictly regulated, since any impairment can have devastating effect on the cell. In living organisms, iron ions are bound to proteins, for storage, transportation, or as a vital part of catalytic centers of enzymes. Transportation of iron ions between different compartments is important for the correct function of the cell. It was recently shown on yeast, how a mitochondrial transporter of iron ions is essential for the synthesis of iron-sulfur clusters of enzymes. This work aims to describe the localization and function of a homologous protein of a parasitical organism Trypanosoma brucei, which causes African trypanosomiasis, also known as sleeping sickness. This parasite is entirely dependent on uptake of iron ions from its host and therefore the utilization of iron ions is studied as a potential therapeutic target. This work is focused on the characterization of protein Mcp17, which is assumed to function as a transporter of iron ions into the mitochondria of T. brucei. Utilizing expression of marked Mcp17, the transporter was confirmed to be localized on the mitochondrial membrane of the cell. Measuring of enzyme activity of selected enzymes indicated that cells with inhibited expression of the gene mcp17...
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The role of iron in the metabolism of the amoeba Naegleria gruberi
Ženíšková, Kateřina ; Konvalinka, Jan (advisor) ; Hlouchová, Klára (referee)
Iron is a biogenic trace element that is vital for all organisms on the planet Earth. This element occurs in biological systems in the form of Fe3+ and Fe2+. These two forms are often incorporated in heme structures or iron-sulfur clusters. Proteins containing iron ions have a wide range of functions in organisms. The main functions include the transport of electrons in the respiratory chain (Rieske's proteins, cytochromes), DNA synthesis (ribonucleotide reductase) and the participation in the Krebs' cycle (aconitase, succinate dehydrogenase). Naegleria gruberi is a nonpathogenic amoeba known for its pathogenic relative Naegleria fowleri. This organism causes the primary amoebic meningoencephalitis. An interesting fact about Naegleria gruberi genome is that it contains genes for both aerobic and anaerobic metabolisms. The purpose of my bachelor work was to investigate the effect of availability of iron ions on metabolism in Naegleria gruberi. Changes in the activities of enzymes from different metabolic pathways were studied including lactate dehydrogenase, isocitrate dehydrogenase, Fe- hydrogenase, aconitase and fumarase. The most significant changes were observed in the activities of alcohol dehydrogenase and Fe-hydrogenase. Key words: Iron, heme, iron-sulfur clusters, availability of iron ions,...
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Metabolic alterations in cancer cells and their implications in the therapy of acute leukemias
Harárová, Alžbeta ; Starková, Júlia (advisor) ; Mrvová, Silvia (referee)
Cancer metabolism differs from that of the healthy cells in several aspects. Aerobic glycolysis (e.g. converting pyruvate to lactate under normoxic conditions) was the first described metabolic alteration of cancer cells. Metabolic alterations have since been described in the tricarboxylic acid cycle, oxidative phosphorylation, in the metabolism of amino acids (especially glutamine, asparagine and serine) and also in the metabolism of fatty acids and cholesterol. The common feature of these changes is the tendency to prefer anabolic pathways, thus enabling fast proliferation of cancer cells. The study of cancer metabolism is particularly important in the case of cancer cells that show resistance to treatment, as their aberrant metabolism is not only a potential diagnostic marker but also a potential therapeutic target. The majority of metabolic alterations have been described for the first time in solid tumors, whereas only recently has the metabolism of acute leukamias gained more attention. Asparaginase is an example of a chemotherapeutic agent that targets a metabolic alteration of leukemic cells. Distinct metabolic profile is also associated with the glucocorticoid resistance. Detailled study of the metabolic alterations of leukemic cells has elucitated the mechanisms of the asparaginase and...
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Metabolism of isoflavonoids in human organism
Šramarová, Pavlína ; Karlíčková, Jana (advisor) ; Jahodář, Luděk (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmaceutical Botany and Ecology Candidate: Bc. Pavlína Šramarová Diploma thesis supervisor: PharmDr. Jana Karlíčková, Ph.D. Title of thesis 2015/2016: Metabolism of isoflavonoids in human organism, pp. 54 Isoflavonoids are subgroup of flavonoids, belonging to the phytoestrogenic compounds. These compounds occur especially in leguminous, mainly in soya (Glycine max (L.) Merr). They have a positive impact on human health, especially for its estrogenic effects, due to which are applied in the fight against osteoporosis, cardiovascular diseases, atherosclerosis and for moderation of menopausal symptoms. Furthermore they exhibit antibacterial activity and protect cells against damage of DNA. This thesis deals with their metabolism and action in human and animal organism, also with the influence of intestinal microflora to transform these isoflavonoids into metabolites, as well as the effects of these metabolites. There are also mentioned these isoflavonoids: daidzein, genistein, biochanin A, formononetin, calycosin, prunetin, puerarin, cladrin, tectorigenin and kakkalid. Key words: isoflavonoids, metabolism, human organism
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Biogenesis of mitochondria in parasitic protist Trypanosoma brucei
Mach, Jan
In last decade, investigations of mitochondria including their various reduced forms such as hydrogenosomes and mitosomes revealed unexpected diversity of this indispensable organelle. Interestingly, the single mitochondrion of parasitic protist Trypanosoma brucei is able to undergo remarkable functional and structural changes reflecting available carbon sources. Moreover, it was proposed that trypanosomes belong among the most ancient eukaryotes and as such, their mitochondria raised high attention of biologists. To contribute to the knowledge of mitochondrial biogenesis and function, we focused on studies of two key mitochondrial processes, the processing of preproteins that are imported to the mitochondria, and mechanism of pyruvate transport to these organelles. Moreover, we also investigated uptake of iron by T. brucei. This metal is essential for function of numerous proteins, particularly for iron-sulfur proteins in mitochondria. Evolutionary history of trypanosomes and their mitochondrion is a question of debates. According to some reports, mitochondrion of trypanosomes represent an ancient form of this organelle, which is supported by identification of putative "archaic" translocase of the outer mitochondrial membrane (ATOM) and finding of only a single type of translocation pore in...
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Factors influencing weight gain in pregnancy
Vodrážková, Nicole ; Kaňková, Šárka (advisor) ; Flegr, Jaroslav (referee)
In this bachelor thesis I described different factors influencing weight gain in each trimester of pregnancy. There are factors influenced by a lifestyle, such as diet, physical activity, smoking, and BMI before pregnancy. There are also factors which are given individual dispositions, changes in metabolism and hormonal status of the organism. On this basis, this thesis deals with the consequences, that has excessive or insufficient weight gain in pregnancy for the mother and her fetus.
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Renal carcinoma bological therapy and the role of cell signaling checkpoints
Černá, Kristýna ; Otavová, Katarína (advisor) ; Tolde, Ondřej (referee)
Principles of targeted biological treatment of metastatic renal cell carcinoma include mainly inhibitors of the tyrosine kinase receptors VEGFR and inhibitors of intracellular mTOR kinase. Across the new healing regimes there are the blockades of immune checkpoints of the immune system cell. Detailed molecular characterization of tumor is necessary not for only aplication of medicaments, but also for the development of drugs that target specific molecular pathway of cell signalization of the carcinoma cells. The work is focused on the description of the signaling pathway mTOR and VEGF in metastatic renal cell carcinoma. It summarizes all validated clinical biomarkers which are used to diagnose and stratify patients for the treatment of mRCC. It also offers insight into the present experiments that are finding new specific molecular markers. That may be the future solution for customized approach in the treatment of renal carcinoma an tumors in general.
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Study of leukemic cells' metabolism in association with response to the therapy
Šimčíková, Markéta ; Starková, Júlia (advisor) ; Čuřík, Nikola (referee)
Acute lymphoblastic leukemia (ALL) is the most common malignant dise- ase in children. Despite great advancements in treatment of this disease, around 15-20 % of patients suffer a relapse. One of the possible reasons for relapse is developed resistance to cytostatic drugs. L-asparaginase is an im- portant chemotherapy component for childhood ALL and resistance to this drug often complicates treatment. To date, causes of developing resistance have not been sufficiently described. This thesis is a part of a greater research project focusing on mechanisms of L-asparaginase's activity and reasons for developing resistance to this chemotherapeutic agent. Differential metabolic requirements of cancerous cells have been described as early as 1924 by O. H. Warburg and they have been subject to scientific inquiry since. This study aimed to describe the relationship between basal metabolic determinants of leukemia cells and their sensitivity to L-asparaginase. For this reason, two metabolic pathways, glycolysis and oxidative phosphorylati- on, were studied in detail using a Seahorse Bioanalyzer. Further, expression of specific genes involved in glycolysis was detected. Content of mitochon- drial reticulum in cells, expression of the asparagine synthetase gene, and cell size were also studied. Experiments were...
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The effect of dihydromyricetin and myricetin on selected biotransformation enzymes
Boštíková, Zdislava ; Hodek, Petr (advisor) ; Koblihová, Jitka (referee)
Flavonoids are natural compounds commonly ingested in herbs and vegetables. They are believed to have a positive impact on human organism, in particular by their antioxidant, hepatoprotective and anti-cancer effects. In these days, it is possible to consume high concentrations of these compounds in form of dietary supplements. However it is not clear, whether flavonoids in such unnaturally high concentrations are still beneficial or rather harmful. It has already been proven, that flavonoids can influence the activity of biotransformation enzymes and interfere e.g. with the process of carcinogenesis and drug metabolism. For that reason it is important to investigate the impact of an increased intake of flavonoids. The aim of this thesis was to investigate the influence of dihydromyricetin (a potential drug to cure alcohol use disorder) and its structurally similar flavonoid myricetin on the activity of enzymes, cytochrome P450 2E1 (CYP2E1) and Nacetyltransferases 1 and 2 (NAT1/2). The research included the determination of the impact of a premedication by these flavonoids on the expression and activity of CYP2E1 and NAT1/2. The inhibition capacity of myricetin and dihydromyricetin towards the activity of CYP2E1 and NAT1/2 was also investigated. After the flavonoid premedication of rats the...
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Metabolic costs of reproduction in vertebrates, particularly in reptiles
Kukačková, Dominika ; Kratochvíl, Lukáš (advisor) ; Hořák, David (referee)
Animal reproduction involves energy expenditures for gamete formation, support of offspring development, and associated behavioural changes. Due to high variability in reproductive traits, reptiles are the ideal study group for this field. Investment in reproductive organs and gametes represent costs of sex products production. The next phase of reproduction is gestation, when females support their developing offspring, which results in additional metabolic costs. Metabolism of pregnant female can be viewed as a sum of resting metabolism, which is the same as in non-pregnant animal, of increased metabolism to support pregnancy, and of embryonic metabolism. Separation of each component is crucial for assessing energy costs of reproduction and for comparison of different reproductive strategies. Certain behavioural changes during reproduction can influence total energy balance as well. These changes include increased locomotion costs or shifts in the thermoregulatory behaviour. Estimation of the real costs of reproduction is a complex matter since a reproduction is a very dynamic process and there are many issues that influence the overall energy consumption of reproducing individuals.
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