Modelling of Metabolic Networks - PowerPoint PPT Presentation

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Modelling of Metabolic Networks

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  1. Modelling of Metabolic Networks Case Study: Martinov model of the methionine cycle

  2. The methionine cycle Methinione combined with ATP to form S-adenosylmethionine (AdoMet) AdoMet donates a methyl group (CH3) to various acceptors (lumped as A) S-adenosylhomocysteine (AdoHcy) converted to homocysteine Homocysteine converted to methionine or to cysteine

  3. The methionine cycle • Model constructed to address three aspects of behaviour: • AdoMet is produced by two distinct enyzmes: MATI and MATIII. MATI inhibited by AdoMetMATIII activated by AdoMet • GNMT transfers CH3 to glycine, forming non-functional sarcosine • As methinoine input rises, [methionine] steady; [AdoMet] and [AdoHcy] steady, then jump at a threshold

  4. Model Network • Two key assumptions: • [methionine], [ATP], [glycine], [A], fixed • Hcy<---> AdoHcy in rapid equilibrium

  5. Model Network Model equations:

  6. Rates:

  7. Behaviour: low [Met] Separation of time-scales: AdoHcy fast, AdoMet slow

  8. Behaviour low [Met] high [Met] Bistability caused by positive feedback of AdoMet on MATIII

  9. Behaviour low [Met] high [Met] standard operation “shunt” active to avoid increased methylation (VMET) rates

  10. Behaviour: bifurcation diagram AdoMet levels steady (lower branch) for low [Met], jumps to high values at threshold (edge of bistable region)