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

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 followi...

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Autores principales: Moreno-Sánchez, Rafael, Saavedra, Emma, Rodríguez-Enríquez, Sara, Olín-Sandoval, Viridiana
Formato: Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2447884/
https://www.ncbi.nlm.nih.gov/pubmed/18629230
http://dx.doi.org/10.1155/2008/597913
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author Moreno-Sánchez, Rafael
Saavedra, Emma
Rodríguez-Enríquez, Sara
Olín-Sandoval, Viridiana
author_facet Moreno-Sánchez, Rafael
Saavedra, Emma
Rodríguez-Enríquez, Sara
Olín-Sandoval, Viridiana
author_sort Moreno-Sánchez, Rafael
collection PubMed
description 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.
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spelling pubmed-24478842008-07-14 Metabolic Control Analysis: A Tool for Designing Strategies to Manipulate Metabolic Pathways Moreno-Sánchez, Rafael Saavedra, Emma Rodríguez-Enríquez, Sara Olín-Sandoval, Viridiana J Biomed Biotechnol Review Article 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. Hindawi Publishing Corporation 2008 2008-07-08 /pmc/articles/PMC2447884/ /pubmed/18629230 http://dx.doi.org/10.1155/2008/597913 Text en Copyright © 2008 Rafael Moreno-Sánchez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Moreno-Sánchez, Rafael
Saavedra, Emma
Rodríguez-Enríquez, Sara
Olín-Sandoval, Viridiana
Metabolic Control Analysis: A Tool for Designing Strategies to Manipulate Metabolic Pathways
title Metabolic Control Analysis: A Tool for Designing Strategies to Manipulate Metabolic Pathways
title_full Metabolic Control Analysis: A Tool for Designing Strategies to Manipulate Metabolic Pathways
title_fullStr Metabolic Control Analysis: A Tool for Designing Strategies to Manipulate Metabolic Pathways
title_full_unstemmed Metabolic Control Analysis: A Tool for Designing Strategies to Manipulate Metabolic Pathways
title_short Metabolic Control Analysis: A Tool for Designing Strategies to Manipulate Metabolic Pathways
title_sort metabolic control analysis: a tool for designing strategies to manipulate metabolic pathways
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2447884/
https://www.ncbi.nlm.nih.gov/pubmed/18629230
http://dx.doi.org/10.1155/2008/597913
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