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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 Coupling Pathways
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
PPP: the oxidative and non-oxidative branches non-oxidative oxidative Coupling w/glycolysis
PPP: oxidative branch Glutathione buffers NADPH: GSH + NADP GSSG + NADPH
Coupling Pathways THE PENTOSE PHOSPHATE PATHWAY
Pentose Phosphate Pathway Reaction map Elemental composition Reactions Compounds
PPP: S Matrix and Simulation Reaction map Stoichiometric matrix
PPP: Phase Portraits In to R5P node PPP exit into R5P synthesis Out off R5P node PPP exit into glycolysis
Coupling Pathways GLYCOLYSIS & the PENTOSE PHOSPHATE PATHWAY
The integrated S matrix Coupling
Biochemistry SIMULATING FLUXES AND CONCENTRATIONS
Glycolysis & PPP:Energy load 50% increase in this rate
Glycolysis & PPP: Phase Portraits vAMP vPYR vATP
Glycolysis & PPP:Redox load Double this rate
Dynamic Simulation Decrease in glycolysis fluxes Increase in PPP fluxes Decrease in glycolytic conc Increase on PPP conc
Systems biology SIMULATING POOLS
Pools Pooling matrix Px Size and dynamics: PSv
Physiology SIMULATING RATIOS
New slide • Add more explanation of the ratios
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