glycolytic oscillation & synchronization. simplified glycolytic pathway
Post on 19-Dec-2015
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Glycolytic Oscillation & Synchronization
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Simplified glycolytic pathway
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Experimental observation 1glycolytic oscillation
• A population of starved yeasts will obtain synchronized glycolytic oscillation after putting glucose and cyanide into the suspension
• Oscillating period 40s (cell cycle 80~100 min) ( if I am the yeast, then oscillating period be like how often I take the final exam)
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Experimental observation 2glycolytic synchronization
• 2 populations of yeasts with 180 degree out of phase will re-synchronize after mixing
• Re-synchronizing time after mixing
about 6 min (i.e. 9 periods of oscillation)
• The amplitude and frequency will maintain the same after the synchronization
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Experimental observation
Two suspensions of yeast cells that oscillate with equal amplitude and opposite phase are mixed. We again observe that macroscopic oscillations develop and that the amplitude increases until a limit is reached asymptotically. This behavior is indicative of limit cycle dynamics.
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Experimental observation
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Experiment Conditionwhy cyanide?
• block respiration • trap acetaldehyde (this compound is found to be the key of
synchronization)
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Discussionwhy oscillate?
• Regulation of PFK
PFK INHIBITOR atp
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Discussionwhy synchronize?
• Possible candidates for synchronizer must have the following properties:
1.can penetrate the cell membrane; 2.oscillates in the extracellular medium as a
result of periodic excretion or absorption by the cells
• Possible candidates: temperature, glucose, Aca
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Possible candidates temperature lose the campaign
• Temperature oscillation due to glycolytic oscillation is 1–2 mK (this is observed in experiments, but simple calculation gives about the same result)
• Observed temperature amplitude can only give rise to a frequency change of 0.2‰
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Possible candidates glucose
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Possible candidatesAca
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Aca forcing experiment
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Aca forcing experiment
• the distance from the center indicates the NADH amplitude a relative to the fully entrained NADH amplitude a entrained, and the angle indicates the phase difference between the forcing and the NADH signal
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Modeling
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Modeling
denotes the ratio of the total cellular volume, VC=nV, to theextracellular volume, VE.
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Modeling
The parameter values of that reference state have been selected in such a way that the metabolite concentrations are in a realistic range for yeast cells
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Simulation Results (for 1000 cells)
intracellular concentrations of each cell are randomly perturbed from nominal values that produce synchronous oscillations
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Simulation Results (mixing 2 sub-populations)
The middle plot shows the average intracellular NADH concentration dynamics and the bottom plot shows computed cell number distributions at 0 min (—), 11.25 min (· · ·), 30 min (– – –) and 45 min (– · – ·)
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Small density of yeast cells
Amplitude dies out as desity decreases
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Small density of yeast cells
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Remarks on the model
• The model can give the trend of oscillation
• However, the amplitude of the oscillation is too large compared to experiments
• The re-synchronizing time is 2~3 times longer than the experimental results
• For small density of yeast cells, the model may not fit
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Thank you!