Distinguishing enzymes using metabolome data for the hybrid dynamic/static method

Nobuyoshi Ishii, Yoichi Nakayama, Masaru Tomita

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background. In the process of constructing a dynamic model of a metabolic pathway, a large number of parameters such as kinetic constants and initial metabolite concentrations are required. However, in many cases, experimental determination of these parameters is time-consuming. Therefore, for large-scale modelling, it is essential to develop a method that requires few experimental parameters. The hybrid dynamic/static (HDS) method is a combination of the conventional kinetic representation and metabolic flux analysis (MFA). Since no kinetic information is required in the static module, which consists of MFA, the HDS method may dramatically reduce the number of required parameters. However, no adequate method for developing a hybrid model from experimental data has been proposed. Results. In this study, we develop a method for constructing hybrid models based on metabolome data. The method discriminates enzymes into static modules and dynamic modules using metabolite concentration time series data. Enzyme reaction rate time series were estimated from the metabolite concentration time series data and used to distinguish enzymes optimally for the dynamic and static modules. The method was applied to build hybrid models of two microbial central-carbon metabolism systems using simulation results from their dynamic models. Conclusion. A protocol to build a hybrid model using metabolome data and a minimal number of kinetic parameters has been developed. The proposed method was successfully applied to the strictly regulated central-carbon metabolism system, demonstrating the practical use of the HDS method, which is designed for computer modelling of metabolic systems.

Original languageEnglish
Article number19
JournalTheoretical Biology and Medical Modelling
Volume4
DOIs
Publication statusPublished - 2007

Fingerprint

Metabolome
Enzymes
Metabolites
Time series
Hybrid Model
Metabolism
Kinetics
Metabolic Flux Analysis
Dynamic models
Module
Fluxes
Carbon
Time Series Data
Kinetic parameters
Dynamic Model
Reaction rates
Computer Modeling
Reaction Rate
System Simulation
Metabolic Networks and Pathways

ASJC Scopus subject areas

  • Health Informatics
  • Medicine(all)

Cite this

Distinguishing enzymes using metabolome data for the hybrid dynamic/static method. / Ishii, Nobuyoshi; Nakayama, Yoichi; Tomita, Masaru.

In: Theoretical Biology and Medical Modelling, Vol. 4, 19, 2007.

Research output: Contribution to journalArticle

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