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Proučevanje fitoestrogenov in derivaov cimetne kisline kot inhibitorjev rekombinantnih človeških hidroksisteroid-dehidrogenaz AKR1C1 in AKR1C3 = Phytoestrogens and cinnamic acid derivatives as inhibitors of recombinant human hydroxysteroid dehydrogenases AKR1C1 in AKR1C3 : diplomsko deloBradač, Mateja, farmacevtkaFitoestrogeni so nesteroidne spojine rastlinskega izvora in sestavni del nase prehrane. So naravni endokrini modulatorji, ki na veè naèinov vplivajo na kompleksni èlovekov endokrini sistem. Delujejo ... kot agonisti ali antagonisti estrogenskih receptorjev (ERŽ in ERŽ), uravnavajo pa tudi delovanje kljuènih encimov v biosintezi estrogenov kot je 17Ž-hidroksisteroid-dehidrogenaza (17Ž-HSD). Kljuèni gradnik fitoestrogenov je cimetna kislina. Estre cimetne kisline kot inhibitorje glivne 17Ž-HSD in fitoestrogene kot inhibitorje èloveske 17Ž-HSD tipa 5 so ze preuèevali, niso pa se testirali fitoestrogenov in derivatov cimetne kisline kot potencialnih inhibitorjev èloveske 20Ž-HSD. AKR1C1 (20Ž-HSD) in AKR1C3 (17Ž-HSD tip 5) sta encima za uravnavanje koncentracije androgenov, estrogenov in progestagenov. Rekombinantna AKR1C1 inAKR1C3 smo izrazili v E.coli v obliki fuzijskih proteinov z glutation-S-transferazo, oèistili z afinitetno kromatografijo na glutation sefarozi in izolirali s cepitvijo s trombinom. Kot potencialne inhibitorje obeh encimov smo testirali 18 fitoestrogenov in 20 derivatov cimetne kisline.AKR1C1 in AKR1C3 katalizirata NADPH odvisno redukcijo progesterona v 20Ž-hidroksiprogesteron in androstendiona v testosteron. Obe reakciji smo spremljali brez in v prisotnosti potencialnih inhibitorjev. Pri encimu AKR1C1 smo s pomoèjo spektrofotometra merili razliko v absorbanci NADPH, pri AKR1C3 pa smo s TLC metodo merili odstotek pretvorbe substrata. Izraèunali smo zaèetne hitrosti in doloèili IC50. Med sinteznimi derivati samo eden inhibira AKR1C3, med fitoestrogeni pa smo nasli veliko inhibitorjev obeh encimov. Za najboljsega inhibitorja AKR1C1 se je izkazal apigenin, AKR1C3 pa najbolje inhibira genistein.Type of material - undergraduate thesisPublication and manufacture - Ljubljana : [Bradač, M.], 2005Language - slovenianCOBISS.SI-ID - 1731953
Author
Bradač, Mateja, farmacevtka
Other authors
Gobec, Stanislav, 1970- |
Lanišnik-Rižner, Tea
Topics
hidroksisteroid-dehidrogenaze |
AKR13C |
inhibitorji |
sinteza |
fitoestrogeni |
metode
Library | Call number – location, accession no. ... | Copy status |
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Faculty of Pharmacy, Lj. | Knjižnica dp 542 Bradač Mateja Proučevanje IN: 0008319 |
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Database name | Field | Year |
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Bradač, Mateja, farmacevtka | |
Gobec, Stanislav, 1970- | 15284 |
Lanišnik-Rižner, Tea | 11699 |
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