1. Lecture #11 Coupling Pathways

2. 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 Coupling to glycolysis Interpreting the results from simulation –Concentrations, fluxes, pools, ratios

3. BIOCHEMISTRY PRIMER

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

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

7. 23DPG

8. THE PENTOSE PHOSPHATE PATHWAY Coupling Pathways

9. Reaction map Pentose Phosphate Pathway Compounds Elemental composition Reactions

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

11. Pathways

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

13. GLYCOLYSIS & the PENTOSE PHOSPHATE PATHWAY Coupling Pathways

14. Coupled pathways: Glycolysis and the pentose pathway

15. The integrated S matrix Coupling

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

17. Kinetics Constants: PERCs

18. SIMULATING FLUXES AND CONCENTRATIONS Biochemistry

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

20. Glycolysis & PPP: Phase Portraits v PYR v ATP v AMP

21. Glycolysis & PPP: Redox load Double this rate

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

23. SIMULATING POOLS Systems biology

24. Pools Pooling matrix Px Size and dynamics: PSv

25. SIMULATING RATIOS Physiology

26. Dynamic Simulation

27. New slide Add more explanation of the ratios

28. 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