Issue: Review and Correct the Stoichiometry and Thermodynamics of Krebs Cycle Reactions

[csmangum]

Issue: Review and Correct the Stoichiometry and Thermodynamics of Krebs Cycle Reactions

Description:
The current simulation of the Krebs Cycle uses fixed energy production values (e.g., 1.0 kJ/mol) for each reaction, which is not accurate. The actual Gibbs free energy changes (( \Delta G^\circ' )) for each enzymatic reaction in the Krebs Cycle vary and can be either exergonic (energy-releasing) or endergonic (energy-consuming). To improve the realism of the simulation, we need to adjust the stoichiometry and thermodynamics of each reaction to reflect accepted biochemical values.

Background:
In biochemistry, the Krebs Cycle is a central metabolic pathway that produces energy through the oxidation of acetyl-CoA, generating NADH, FADH₂, and ATP/GTP. Each step in the cycle involves a specific enzyme and yields different amounts of energy based on the Gibbs free energy change of the reaction.

For example:

• Citrate Synthase catalyzes the condensation of acetyl-CoA with oxaloacetate to form citrate, releasing energy.
• Isocitrate Dehydrogenase converts isocitrate to α-ketoglutarate and produces NADH, releasing approximately -21 kJ/mol of energy.

Currently, the simulation simplifies these reactions with arbitrary fixed energy values, leading to unrealistic energy calculations.

Tasks:

1. Research Gibbs Free Energy Changes:

   • Collect ( \Delta G^\circ' ) values for each reaction in the Krebs Cycle from reliable biochemical sources (e.g., textbooks, research papers).
   • Document the reference values in a shared resource file (e.g., krebs_cycle_references.md).

2. Update Reaction Stoichiometry:

   • Verify that the input and output substrates for each reaction match the actual biochemistry.
   • Adjust the number of molecules consumed and produced to ensure accurate stoichiometric balance.

3. Adjust Energy Calculations:

   • Replace the fixed 1.0 kJ/mol energy value with the researched ( \Delta G^\circ' ) for each reaction.
   • Modify the simulation logic to account for the variability in energy release or consumption in each reaction.

4. Testing and Validation:

   • Run test cases to ensure that the updated reactions produce expected outputs.
   • Validate the overall energy balance of a single turn of the Krebs Cycle.
   • Ensure that the sum of energy changes aligns with known ATP yield per cycle (typically around -40 to -50 kJ/mol).

Acceptance Criteria:

• All reactions in the Krebs Cycle have updated, accurate ( \Delta G^\circ' ) values.
• Substrate stoichiometry is corrected and balanced for each reaction.
• Total energy yield per cycle falls within the expected range.
• The updated simulation produces consistent and realistic results in line with known biochemical pathways.

Expected Outcome:
A more accurate simulation of the Krebs Cycle that produces realistic energy values, improving the fidelity of the modeled biochemical process.