Lecture #11 Coupling Pathways. Outline Some biochemistry The pentose pathway; –a central metabolic pathway producing pentoses and NADPH Co-factor coupling.

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Presentation transcript:

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

BIOCHEMISTRY PRIMER

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

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

23DPG

THE PENTOSE PHOSPHATE PATHWAY Coupling Pathways

Reaction map Pentose Phosphate Pathway Compounds Elemental composition Reactions

PPP: S Matrix and Simulation Stoichiometric matrix Reaction map

Pathways

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

GLYCOLYSIS & the PENTOSE PHOSPHATE PATHWAY Coupling Pathways

Coupled pathways: Glycolysis and the pentose pathway

The integrated S matrix Coupling

Gly & PPP: Selected basis based on biochemical intuition

Kinetics Constants: PERCs

SIMULATING FLUXES AND CONCENTRATIONS Biochemistry

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

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

Glycolysis & PPP: Redox load Double this rate

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

SIMULATING POOLS Systems biology

Pools Pooling matrix Px Size and dynamics: PSv

SIMULATING RATIOS Physiology

Dynamic Simulation

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