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Lecture #11

Lecture #11. Coupling Pathways. Outline. Some biochemistry The pentose pathway; a central metabolic pathway producing pentoses and NADPH Co-factor coupling NADPH, CO 2 , GSH The stoichiometric matrix for PPP Its null spaces Setting up a simulation model Steady state

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Lecture #11

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  1. Lecture #11 Coupling Pathways

  2. Outline • Some biochemistry • The pentose pathway; • a central metabolic pathway producing pentoses and NADPH • Co-factor coupling • NADPH, CO2, GSH • The stoichiometric matrix for PPP • Its null spaces • Setting up a simulation model • Steady state • Coupling to glycolysis • Interpreting the results from simulation • Concentrations, fluxes, pools, ratios

  3. BIOCHEMISTRY PRIMER

  4. PPP: the oxidative and non-oxidative branches non-oxidative oxidative Coupling w/glycolysis

  5. PPP: oxidative branch Glutathione buffers NADPH: GSH + NADP  GSSG + NADPH

  6. 23DPG

  7. Coupling Pathways THE PENTOSE PHOSPHATE PATHWAY

  8. Pentose Phosphate Pathway Reaction map Elemental composition Reactions Compounds

  9. PPP: S Matrix and Simulation Reaction map Stoichiometric matrix

  10. Pathways

  11. PPP: Phase Portraits In to R5P node PPP exit into R5P synthesis Out off R5P node PPP exit into glycolysis

  12. Coupling Pathways GLYCOLYSIS & the PENTOSE PHOSPHATE PATHWAY

  13. Coupled pathways: Glycolysis and the pentose pathway

  14. The integrated S matrix Coupling

  15. Gly & PPP: Selected basis based on biochemical intuition

  16. Kinetics Constants: PERCs

  17. Biochemistry SIMULATING FLUXES AND CONCENTRATIONS

  18. Glycolysis & PPP:Energy load 50% increase in this rate

  19. Glycolysis & PPP: Phase Portraits vAMP vPYR vATP

  20. Glycolysis & PPP:Redox load Double this rate

  21. Dynamic Simulation Decrease in glycolysis fluxes Increase in PPP fluxes Decrease in glycolytic conc Increase on PPP conc

  22. Systems biology SIMULATING POOLS

  23. Pools Pooling matrix Px Size and dynamics: PSv

  24. Physiology SIMULATING RATIOS

  25. Dynamic Simulation

  26. New slide • Add more explanation of the ratios

  27. Summary • The pentose pathway can be described in a similar way as glycolysis • A simulation model can be formulated • The two stoichiometric matrices describing the two pathways can be merged • The coupling metabolites are G6P, F6P, GAP • The structure of the null space for glycolysis alone and the coupled pathways is similar • Pools and ratios can be formed as before • Simulation to 50% increase in rate of utilization of ATP is similar to that of glycolysis alone • Systems biology shows up • Definition of pathways, definition of pools

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