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Human Membrane-bound Carbonyl Reductases
Štambergová, Hana ; Wsól, Vladimír (advisor) ; Wimmerová, Michaela (referee) ; Šebela, Marek (referee)
ABSTRACT Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Biochemical Sciences Candidate Mgr. Hana ŠTAMBERGOVÁ Supervisor prof. Ing. Vladimír WSÓL, Ph.D. Title of Doctoral Thesis Human membrane-bound carbonyl reductases Human membrane bound enzymes involved in the metabolism of carbonyl containing compounds consitute a highly interesting group of enzymes. Despite the great effort of scientists over the world most of them still remain uncharacterized, mainly those from the large short-chain dehydrogenases/reductases superfamily (SDR). At present, 75 SDR members have been indentified in the human genome whereas only 20 % of them is considered to be well characterized. On the other hand 30 % SDRs remain completly uncharacterized. SDR enzymes are involved in the metabolism of steroids, saccharides, retinoids or prostaglandins and therefore play a crucial role in a number of physiological pathways as well as several serious diseases (e.g. hormon dependent cancer, metabolic syndrome, diabetes mellitus). Moreover, SDR proteins contribute to the biotransformation of some xenobiotic compounds. Several SDR enzymes have been identified to be involved in the phase I metabolism of drugs such as doxorubicin, dolasetron, benfluron, metyrapone or ketoprofen, but so far only one...
Production of the ovarian hormones in breast tumours.
Štambergová, Hana ; Dršata, Jaroslav (referee) ; Hochmann, Jiří (advisor)
1 SUMMARY The breast cancer affects over one million women all over the world every year. Approximately 60 - 80 % of these tumours are declared as hormone sensitive, which means they are able to respond on a stimulation of estrogens that work as cocancerogens. The breast cancer incidence increases according to an age, a majority of new cases is detected during the postmenopausal period when the ovaries ceased to be functional. In postmenopausal patients the local estrogen production becomes a considerable stimulating growth factor of tumours. In this thesis we have brought together a review of enzymes participating on the intratumoral biosynthesis of estrogens or estradiol. The enzymes responsible for the local synthesis include predominantly the aromatase, 17β-hydroxysteroid dehydrogenases and steroid sulphatase. We have specified by each type of the enzymes its biochemistry, biological characteristics and also its engagement in a breast cancerogenesis as well as their advantage as a pharmacological target. We have also placed pieces of information about members of the AKR1C subfamily. Professor Wsól from the department of biochemistry sciences of our faculty focuses on their study (a participation on a biodegradation of carbonyl groups xenobiotics). AKR1C3 (also called 17β-hydroxysteroid dehydrogenase...

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