On the relationship between thermodynamic disequilibrium ratio and flux control of metabolic pathways

Rust, Frederik Christoffel (2021-12)

Thesis (MSc)--Stellenbosch University, 2021.

Thesis

ENGLISH ABSTRACT: This study presents a methodology to determine and compare flux control co- efficients, as defined in the metabolic control analysis framework, with dise- quilibrium ratios of reactions in metabolic pathways at steady-state. This is accomplished in the form of an automated computational algorithm written in Wolfram Mathematica that 1) retrieves models from online repositories via an Application Programming Interface (API), 2) calculates flux control coefficients, and 3) determines disequilibrium ratios using the symbolic forms of reaction rate equations. The analysis was started with 778 models obtained from the JWS Online and Biomodels databases, of which 164 remained, leading to a total of 1234 reac- tions, after testing for suitability of the models and reactions for the analysis. Probability density plots of the flux control coefficients against the disequilib- rium ratios showed clearly that the vast majority of reactions with a flux con- trol coefficient, on their own flux, greater than 0.25 had a disequilibrium ratio smaller than 0.2. Furthermore the plot shows that the majority of reactions have flux control coefficients smaller than 0.2, and that reactions tend to have either high (>0.6) or low (<0.3) disequilibrium ratios, which was strongly influenced by presence or absence of product sensitivity in the denominator of the rate equations.

AFRIKAANSE OPSOMMING: Hierdie studie bied ’n metodologie aan om fluksiekontrole-koëffisiënte, soos gedefinieer in die metaboliese kontrole analise raamwerk,te bepaal en te verge- lyk met disekwilibriumverhoudings van reaksies in metaboliese padweë by ’n bestendige toestand. Dit word bewerkstellig in die vorm van ’n outomatiese berekeningsalgoritme geskryf in Wolfram Mathematica wat 1) modelle van aan- lynbewaarplekke via ’n programmeringskoppelvlak (API) haal, 2) fluksiekontrole- koëffisiënte bereken, en 3) disekwilibriumverhoudings bepaal deur gebruik te maak van die simboliese vorms van reaksiesnelheidsvergelykings. Die ontleding is begin met 778 modelle verkry vanaf die JWS Online en Biomod- els databasisse, waarvan 164 oorgebly het, wat gelei het tot ’n totaal van 1234 reaksies, na toetsing vir geskiktheid van die modelle en reaksies vir die analise. Waarskynlikheidsdigtheid-grafieke van die fluskiekontrolekoëffisiënte teenoor die disekwilibriumverhoudings het duidelik getoon dat die oorgrote meerder- heid reaksies met ’n fluskiekontrolekoëffisiënt groter as 0.25 ’n disekwilibri- umverhouding kleiner as 0.2 gehad het. Verder toon die grafiek dat die meerder- heid reaksies fluskiekontrolekoëffisiënte kleiner as 0.2 het, en dat reaksies geneig is om óf hoë (>0.6) óf lae (<0.3) disekwilibriumverhoudings te hê, wat sterk beïnvloed is deur die teenwoordigheid of afwesigheid van produksensitiwiteit in die noemer van die snelheidsvergelykings.

Please refer to this item in SUNScholar by using the following persistent URL: http://hdl.handle.net/10019.1/124261
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