Strategies for representing metabolic pathways within biochemical systems theory: reversible pathways

Area of Science:

• Biochemistry
• Systems Biology
• Computational Biology

Background:

• Complex biochemical systems require systematic analysis methods.
• Biochemical Systems Theory (BST) is a prominent framework, with S-system representation being a key variant.
• Existing S-system representations primarily use an
• irreversible
• strategy for flux aggregation.

Purpose of the Study:

• To compare two distinct strategies for generating S-system representations:
• "reversible" and "irreversible".
• To evaluate their performance in modeling biochemical systems, particularly reversible pathways.

Main Methods:

• Developed and analyzed two S-system representation strategies:
• "reversible" (separating incoming/outgoing fluxes) and "irreversible" (aggregating forward/reverse fluxes).
• Compared their predictive accuracy for steady-state flux, transient responses, and robustness.

Main Results:

• All S-system representations yield similar predictions for concentration changes.
• The
• "reversible" strategy outperforms the
• "irreversible" strategy in accuracy and robustness.
• Only the
• "reversible" strategy accurately models amphibolic pathways with flux reversal.

Conclusions:

• The
• "reversible" S-system strategy is superior for modeling biochemical systems.
• This method enhances the accuracy and robustness of predictions, especially for pathways with physiological flux reversal.
• BST, particularly with the reversible S-system approach, provides a powerful tool for understanding complex biochemical dynamics.