The effect of adenylate kinase on the glycolytic oscillations of Saccharomyces cerevisiae

Van Wyk, Morne (2019-02)

Thesis (MSc)--Stellenbosch University, 2019.

Thesis

ENGLISH ABSTRACT: The regulation of phosphofructokinase (PFK) by ATP and AMP is a necessary feature for glycolytic oscillations. The enzyme adenylate kinase (AK) is responsible for the interconversion of ATP + AMP 2 ADP, and so in uences the regulation of PFK. We present here, both experimentally and through model simulations, that a decrease in AK activity results in an increase in period time of the glycolytic oscillations. We show, for the rst time, that AK is a necessary component of these oscillations and an absence of AK activity results in no oscillations. Using an existing model for glycolytic oscillations, we incorperate a mechanistic equation for AK activity with parameters determined from ts to enzyme kinetic data. In the subsequent model simulations we piece apart the individual contributions of ATP and AMP towards these oscillations and nd that a reduction in AK activity leads to changes in both ATP and AMP oscillation phase and amplitude. This causes changes in PFK T and R state switching, increasing the period time of the oscillations.

AFRIKAANSE OPSOMMING: Die regulering van fosfofruktokinase (PFK) deur ATP en AMP is 'n noodsaaklike kenmerk vir glikolitiese ossillasies. Die ensiem adenylaatkinase (AK) is verantwoordelik vir die interkonversie van ATP + AMP 2 ADP, en beà nvloed ook die regulering van PFK. Ons bied hier, beide eksperimenteel en deur middel van simulasies, aan dat 'n afname in AK-aktiwiteit 'n toename in die tydperk van die glikolitiese ossillasies tot gevolg het. Ons wys vir die eerste keer dat AK 'n noodsaaklike komponent van hierdie ossillasies is en dat 'n afwesigheid van AK-aktiwiteit geen ossillasies tot gevolg het nie. Deur 'n bestaande model vir glikolitiese ossillasies te gebruik, inkorporeer ons 'n meganistiese vergelyking vir AK-aktiwiteit met parameters wat bepaal word uit pasings tot ensiemkinetiese data. In die daaropvolgende model simulasies onderskei ons die individuele bydraes van ATP en AMP na hierdie ossillasies en vind dat 'n vermindering in AK aktiwiteit lei tot veranderinge in beide ATPen AMP-ossillasiefase en amplitude. Dit veroorsaak veranderinge in PFK T en R staatskakelaars, wat die tydperkstyd van die ossillasies verhoog.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/105593
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