Systems biology from micro-organisms to human metabolic diseases: the role of detailed kinetic models

Barbara M. Bakker*, Karen van Eunen, Jeroen A. L. Jeneson, Natal A. W. van Riel, Frank J. Bruggeman, Bas Teusink

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

17 Citations (Scopus)

Abstract

Human metabolic diseases are typically network diseases. This holds not only for multifactorial diseases, such as metabolic syndrome or Type 2 diabetes, but even when a single gene defect is the primary cause, where the adaptive response of the entire network determines the severity of disease. The latter may differ between individuals carrying the same mutation. Understanding the adaptive responses of human metabolism naturally requires a systems biology approach. Modelling of metabolic pathways in microorganisms and some mammalian tissues has yielded many insights, qualitative as well as quantitative, into their control and regulation. Yet, even for a well-known pathway such as glycolysis, precise predictions of metabolite dynamics from experimentally determined enzyme kinetics have been only moderately successful. In the present review, we compare kinetic models of glycolysis in three cell types (African trypanosomes, yeast and skeletal muscle), evaluate their predictive power and identify limitations in our understanding. Although each of these models has its own merits and shortcomings, they also share common features. For example, in each case independently measured enzyme kinetic parameters were used as input. Based on these 'lessons from glycolysis', we will discuss how to make best use of kinetic computer models to advance our understanding of human metabolic diseases.

Original languageEnglish
Pages (from-to)1294-1301
Number of pages8
JournalBiochemical Society Transactions
Volume38
DOIs
Publication statusPublished - Oct-2010

Keywords

  • kinetic model of metabolism
  • Saccharomyces cerevisiae
  • Silicon Cell
  • skeletal muscle
  • Trypanosoma brucei
  • FORM TRYPANOSOMA-BRUCEI
  • SACCHAROMYCES-CEREVISIAE
  • GLYCOLYTIC FLUX
  • YEAST
  • CELLS
  • OSCILLATIONS
  • UNDERSTOOD
  • PATHWAYS
  • GLUCOSE
  • ENZYMES

Cite this