Metabolic Control Analysis: A Tool for Designing Strategies to Manipulate Metabolic Pathways

Abstract

The traditional experimental approaches used for changing the flux or the concentration of a particular metabolite of a metabolic pathway have been mostly based on the inhibition or over-expression of the presumed rate-limiting step. However, the attempts to manipulate a metabolic pathway by following such approach have proved to be unsuccessful. Metabolic Control Analysis (MCA) establishes how to determine, quantitatively, the degree of control that a given enzyme exerts on flux and on the concentration of metabolites, thus substituting the intuitive, qualitative concept of rate limiting step. Moreover, MCA helps to understand (i) the underlying mechanisms by which a given enzyme exerts high or low control and (ii) why the control of the pathway is shared by several pathway enzymes and transporters. By applying MCA it is possible to identify the steps that should be modified to achieve a successful alteration of flux or metabolite concentration in pathways of biotechnological (e.g., large scale metabolite production) or clinical relevance (e.g., drug therapy). The different MCA experimental approaches developed for the determination of the flux-control distribution in several pathways are described. Full understanding of the pathway properties when is working under a variety of conditions can help to attain a successful manipulation of flux and metabolite concentration.

DOI: 10.1155/2008/597913

Extracted Key Phrases

17 Figures and Tables

0501002008200920102011201220132014201520162017
Citations per Year

299 Citations

Semantic Scholar estimates that this publication has 299 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{MorenoSanchez2008MetabolicCA, title={Metabolic Control Analysis: A Tool for Designing Strategies to Manipulate Metabolic Pathways}, author={Rafael Moreno-Sanchez and Emma Saavedra and Sara Rodr{\'i}guez-Enr{\'i}quez and Viridiana Ol{\'i}n-Sandoval}, journal={Journal of Biomedicine and Biotechnology}, year={2008}, volume={2008}, pages={379 - 385} }