Biomaterial Database

Design of metabolic control for large flux changes. 1996

S Thomas, and D A Fell

School of Biological and Molecular Sciences, Oxford Brookes University, Headington, U.K.

Metabolic Control Analysis has invalidated many traditional biochemical concepts of control, in particular the rate-limiting step. However, it has not been used to question the mechanisms by which pathway flux is thought to be controlled, such as the action of allosteric effectors or of covalent modification mechanisms. Here we use Control Analysis and computer simulation to examine the response of pathway segments to change in flux imposed by action on an enzyme outside the segment. Whether these segments contain near-equilibrium enzyme-catalysed reactions, cooperative enzymes, feedforward activation loops or feedback inhibition loops, their responses are significantly different from those observed in vivo. In particular, they do not exhibit the remarkable degrees of metabolite homoeostasis during large flux changes that have frequently been observed experimentally. On the other hand, near-constant levels of metabolites in spite of large changes of flux are consistent with our recent proposal that multi-site modulation--simultaneous activation of many pathway steps-is the normal method by which metabolism is controlled.

UI	MeSH Term	Description	Entries
D008954	Models, Biological	Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.	Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D003198	Computer Simulation	Computer-based representation of physical systems and phenomena such as chemical processes.	Computational Modeling,Computational Modelling,Computer Models,In silico Modeling,In silico Models,In silico Simulation,Models, Computer,Computerized Models,Computer Model,Computer Simulations,Computerized Model,In silico Model,Model, Computer,Model, Computerized,Model, In silico,Modeling, Computational,Modeling, In silico,Modelling, Computational,Simulation, Computer,Simulation, In silico,Simulations, Computer
D004798	Enzymes	Biological molecules that possess catalytic activity. They may occur naturally or be synthetically created. Enzymes are usually proteins, however CATALYTIC RNA and CATALYTIC DNA molecules have also been identified.	Biocatalyst,Enzyme,Biocatalysts
D006706	Homeostasis	The processes whereby the internal environment of an organism tends to remain balanced and stable.	Autoregulation
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D019295	Computational Biology	A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.	Bioinformatics,Molecular Biology, Computational,Bio-Informatics,Biology, Computational,Computational Molecular Biology,Bio Informatics,Bio-Informatic,Bioinformatic,Biologies, Computational Molecular,Biology, Computational Molecular,Computational Molecular Biologies,Molecular Biologies, Computational