Dynamics of uptake and metabolism of small molecules in cellular response systems
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Dynamics of uptake and metabolism of small molecules in cellular response systems. / Werner, Maria; Semsey, Szabolcs; Sneppen, Kim; Krishna, Sandeep.
In: P L o S One, Vol. 4, No. 3, 2009, p. e4923.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Dynamics of uptake and metabolism of small molecules in cellular response systems
AU - Werner, Maria
AU - Semsey, Szabolcs
AU - Sneppen, Kim
AU - Krishna, Sandeep
PY - 2009
Y1 - 2009
N2 - BACKGROUND: Proper cellular function requires uptake of small molecules from the environment. In response to changes in extracellular conditions cells alter the import and utilization of small molecules. For a wide variety of small molecules the cellular response is regulated by a network motif that combines two feedback loops, one which regulates the transport and the other which regulates the subsequent metabolism.RESULTS: We analyze the dynamic behavior of two widespread but logically distinct two-loop motifs. These motifs differ in the logic of the feedback loop regulating the uptake of the small molecule. Our aim is to examine the qualitative features of the dynamics of these two classes of feedback motifs. We find that the negative feedback to transport is accompanied by overshoot in the intracellular amount of small molecules, whereas a positive feedback to transport removes overshoot by boosting the final steady state level. On the other hand, the negative feedback allows for a rapid initial response, whereas the positive feedback is slower. We also illustrate how the dynamical deficiencies of one feedback motif can be mitigated by an additional loop, while maintaining the original steady-state properties.CONCLUSIONS: Our analysis emphasizes the core of the regulation found in many motifs at the interface between the metabolic network and the environment of the cell. By simplifying the regulation into uptake and the first metabolic step, we provide a basis for elaborate studies of more realistic network structures. Particularly, this theoretical analysis predicts that FeS cluster formation plays an important role in the dynamics of iron homeostasis.
AB - BACKGROUND: Proper cellular function requires uptake of small molecules from the environment. In response to changes in extracellular conditions cells alter the import and utilization of small molecules. For a wide variety of small molecules the cellular response is regulated by a network motif that combines two feedback loops, one which regulates the transport and the other which regulates the subsequent metabolism.RESULTS: We analyze the dynamic behavior of two widespread but logically distinct two-loop motifs. These motifs differ in the logic of the feedback loop regulating the uptake of the small molecule. Our aim is to examine the qualitative features of the dynamics of these two classes of feedback motifs. We find that the negative feedback to transport is accompanied by overshoot in the intracellular amount of small molecules, whereas a positive feedback to transport removes overshoot by boosting the final steady state level. On the other hand, the negative feedback allows for a rapid initial response, whereas the positive feedback is slower. We also illustrate how the dynamical deficiencies of one feedback motif can be mitigated by an additional loop, while maintaining the original steady-state properties.CONCLUSIONS: Our analysis emphasizes the core of the regulation found in many motifs at the interface between the metabolic network and the environment of the cell. By simplifying the regulation into uptake and the first metabolic step, we provide a basis for elaborate studies of more realistic network structures. Particularly, this theoretical analysis predicts that FeS cluster formation plays an important role in the dynamics of iron homeostasis.
KW - Cells
KW - Homeostasis
KW - Iron
KW - Models, Theoretical
KW - Journal Article
KW - Research Support, Non-U.S. Gov't
U2 - 10.1371/journal.pone.0004923
DO - 10.1371/journal.pone.0004923
M3 - Journal article
C2 - 19290058
VL - 4
SP - e4923
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 3
ER -
ID: 163917471