Utjecaj promjene temperature na selektivnost inhibicije bambuterolom i stereoselektivnost kolinesteraza

master's thesis

• Title (english): The effect of temperature on bambuterol inhibition selectivity and cholinesterase stereoselectivity
• Author: Tihana Dropulić
• Mentor: Višnja Gaurina Srček (mentor)
• Granter: University of Zagreb; Faculty of Food Technology and Biotechnology; (Department of Biochemical Engineering); (Laboratory for Cell Technology, Application and Biotransformations); Zagreb
• Defense date and country: 2013-01-31, Croatia
• Scientific / art field, discipline and subdiscipline: BIOTECHNICAL SCIENCES; Biotechnology

Abstract

Bambuterol je ireverzibilni inhibitor kolinesteraza koji selektivno inhibira butirilkolinesterazu (BChE; EC 3.1.1.8). Za inhibiciju acetilkolinesteraze (AChE; EC 3.1.1.7) i BChE s racemičnim, (R)- i (S)-bambuterolom određene su sveukupne konstante brzine inhibicije (ki) pri 12, 20, 25, 30 i 37 °C. Selektivnost inhibicije je izražena kao omjer ki konstanti određenih za inhibiciju AChE i BChE s racemičnim bambuterolom, dok je stereoselektivnost BChE određena kao omjer ki konstanti za (R)- i (S)-bambuterol. Za BChE je pokazano da brzina inhibicije raste linearno s porastom temperature do 30 °C dok je brzina inhibicije pri 37 °C jednaka onoj na 25 °C. Utvrđena ovisnost brzine inhibicije o temperaturi ukazuje da se kod 37 °C mijenja odnos konstanti brzina koje opisuju pojedine reakcije složenog mehanizma inhibicije BChE bambuterolom definiranog ki konstantom, u odnosu na temperature do 30 °C. Porastom temperature selektivnost inhibicije bambuterolom opada, dok se stereoselektivnost BChE prema enantiomerima bambuterola s promjenom temperature ne mijenja.

Abstract (english)

Bambuterol is an irreversible cholinesterase inhibitor that selectively inhibits butyrylcholinesterase (BChE, EC 3.1.1.8). The overall inhibition rate constant (ki) for the inhibition of acetylcholinesterase (AChE; EC 3.1.1.7) and BChE with racemic, (R) - or (S)-bambuterol were determined at 12, 20, 25, 30 and 37 °C. The selectivity of inhibition was expressed as the ratio of ki constants for the inhibition of AChE and BChE with racemic bambuterol, while BChE stereoselectivity was defined as the ratio of ki constants for (R)- and (S)-bambuterol. The inhibition rate of BChE linearly increased at temperatures up to 30 °C, whereas at 37 °C the inhibition rate decreased and was similar to the inhibition rate determined at 25 °C. An increase in temperature affects the ratio of constants describing the particular reactions in the mechanism of BChE inhibition by bambuterol. The ratio of particular constants changed at 37 °C compared to that at temperatures below 30°C. Increasing the temperature caused a decrease in the selectivity of cholinesterase inhibition by bambuterol, while the stereoselectivity of BChE toward bambuterol enantiomers did not change with temperature.

• Keywords: AChE; BChE; enantiomeri; bambuterol; karbamat; konstante brzine inhibicije
• Keywords (english): AChE; BChE; enantiomers; bambuterol; carbamate; inhibition rate constants
• Language: croatian
• URN:NBN: urn:nbn:hr:159:769147
• Study programme: Title: Molecular Biotechnology; Study programme type: university; Study level: graduate; Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2017-05-04 12:15:01