Thermodynamic constraints on the regulation of metabolic fluxes.
Nutrition and metabolism are fundamental to cellular function. Metabolic activity (i.e. rates of flow, most commonly referred to as flux) is constrained by thermodynamics and regulated by the activity of enzymes. The general principles that relate biological and physical variables to metabolic control are incompletely understood. Using metabolic control analysis and computer simulations in several models of simplified metabolic pathways, we derive analytical expressions that define relationships between thermodynamics, enzyme activity, and flux control. The relationships are further analyzed in a mathematical model of glycolysis as an example of a complex biochemical pathway. We show that metabolic pathways that are very far from equilibrium are controlled by the activity of upstream enzymes. However, in general, regulation of metabolic fluxes by an enzyme has a more adaptable pattern, which relies more on distribution of free energy among reaction steps in the pathway than on the thermodynamic properties of the given enzyme. These findings show how the control of metabolic pathways is shaped by thermodynamic constraints of the given pathway.
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Related Subject Headings
- Thermodynamics
- Models, Biological
- Metabolic Networks and Pathways
- Kinetics
- Glycolysis
- Biochemistry & Molecular Biology
- 34 Chemical sciences
- 32 Biomedical and clinical sciences
- 31 Biological sciences
- 11 Medical and Health Sciences
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Thermodynamics
- Models, Biological
- Metabolic Networks and Pathways
- Kinetics
- Glycolysis
- Biochemistry & Molecular Biology
- 34 Chemical sciences
- 32 Biomedical and clinical sciences
- 31 Biological sciences
- 11 Medical and Health Sciences