title: 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.
authors.affiliation: Departamento de Bioquímica, Instituto Nacional de Cardiología, Juan Badiano no. 1, Colonia Sección 16, Tlalpan, México DF 14080, Mexico. rafael.moreno@cardiologia.org.mx
authors.forename: Rafael
authors.initials: R
authors.lastname: Moreno-Sánchez
authors.forename: Emma
authors.initials: E
authors.lastname: Saavedra
authors.forename: Sara
authors.initials: S
authors.lastname: Rodríguez-Enríquez
authors.forename: Viridiana
authors.initials: V
authors.lastname: Olín-Sandoval
mesh_terms: D005818:Genetic Engineering; D006019:Glycolysis; D007700:Kinetics; D053858:Metabolic Networks and Pathways; D008954:Models, Biological; D008956:Models, Chemical; D010732:Phosphofructokinase-1 / Q000378:metabolism
chemical_list: D010732:Phosphofructokinase-1