Thesis (PhD (Biochemistry))--University of Stellenbosch, 2011. / ENGLISH ABSTRACT: Metabolic Control Analysis (MCA) provides a powerful quantitative framework for understanding
and explaining the control and regulation within a cellular system. MCA
allows the global control of a steady-state system to be quantified in terms of control
coeficients, which we can express in terms of the local properties referred to as elasticity
coeficients. MCA relates elasticities to control coeficients through a matrix inversion,
thus allowing scientists to predict and quantify how the kinetics of the individual enzymes
affect the systemic behaviour of cellular systems. Traditionally we solved this
problem numerically, while we used algebraic and symbolic control analysis techniques
less frequently. By using symbolic algebraic computation we present a general implementation
of the symbolic matrix inversion of MCA, known as SymCA, which requires
only the description of any allosteric modifier interactions and the stoichiometry of a
cellular system. The algebraic expressions generated allow an in-depth analysis of the
distribution of the control within a system and also of the parameters which exhibit
the greatest effect on this control distribution. This also applies when the exact values
for the elasticities or control coeficients are unknown. We have demonstrated that by
quantifying the control patterns, referred to as `routes of regulation', inherent in all control
coeficient expressions, we can gain insight into how perturbations are propagated
through a cellular system and which regulatory pathways are favoured under changing
conditions. / AFRIKAANSE OPSOMMING: Metaboliese Kontrole-Analise (MKA) bied 'n kragtige kwantitatiewe raamwerk om die
beheer en regulering binne sellulere sisteme te verstaan en te verduidelik. 'n Sleutelaspek
van MKA is dat die globale beheer van 'n sisteem met 'n bestendige toestand gekwantifiseer kan word in terme van kontrole-koefisente en dat hierdie koefisente uitgedruk
kan word in terme van die sisteem se lokale eienskappe, genaamd elastisiteitskoefisente.
Deur van matriksinversie gebruik te maak kan MKA die verband tussen elastisiteitskoefisente en kontrole-koefisente aflei wat mens in staat stel om te sien hoe die kinetika
van die individuele ensiemreaksies die sisteemgedrag op sellulere vlak beinvloed. Die
probleem word tradisioneel hoofsaaklik op numeriese wyse bereken terwyl die gebruik
van algebraiese en simboliese kontrole-analise minder gereeld gebruik word. In hierdie
proefskrif verskaf ons, deur van simboliese algebraiese metodes gebruik te maak, 'n generiese
implementasie van die simboliese matriksinversie van MKA, genaamd SymCA, wat
slegs 'n beskrywing van 'n sellulere sisteem se allosetriese interaksies en die stoichiometrie
benodig. Die algebraiese uitdrukkings sodanig gegenereer stel mens in staat om
'n in-diepte analise te doen om vas te stel waar die beheer binne 'n sisteem le, asook
watter parameters die grootste effek op die kontrole-verspreiding het. Dit geld selfs in
die geval waar die presiese waardes van die elastisiteitskoefisente of kontrole-koefisente
onbekend is. Hierdie proefskrif demonstreer hoe die kwantifisering van kontrole-patrone,
ook gesien as 'roetes van regulering', wat inherent is aan kontrole-koefisent vergelykings,
mens in staat stel om te sien hoe perturbasies in 'n sellulere sisteem voortplant en
watter regulatoriese paaie bevoordeel word onder veranderde kondisies.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:sun/oai:scholar.sun.ac.za:10019.1/6627 |
| Date | 03 1900 |
| Creators | Akhurst, Timothy John |
| Contributors | Rohwer, J. M., Hofmeyr, J.-H. S., University of Stellenbosch. Faculty of Science. Dept. of Biochemistry. |
| Publisher | Stellenbosch : University of Stellenbosch |
| Source Sets | South African National ETD Portal |
| Language | en_ZA |
| Detected Language | Unknown |
| Type | Thesis |
| Rights | University of Stellenbosch |
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