Dynamics of uptake and metabolism of small molecules in cellular response systems.
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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2009-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2654506?pdf=render |
| _version_ | 1818413914657914880 |
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| author | Maria Werner Szabolcs Semsey Kim Sneppen Sandeep Krishna |
| author_facet | Maria Werner Szabolcs Semsey Kim Sneppen Sandeep Krishna |
| author_sort | Maria Werner |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-14T11:10:46Z |
| format | Article |
| id | doaj.art-ff75c12474c949a8bc49b38b53e9c738 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T11:10:46Z |
| publishDate | 2009-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-ff75c12474c949a8bc49b38b53e9c7382022-12-21T23:04:17ZengPublic Library of Science (PLoS)PLoS ONE1932-62032009-01-0143e492310.1371/journal.pone.0004923Dynamics of uptake and metabolism of small molecules in cellular response systems.Maria WernerSzabolcs SemseyKim SneppenSandeep KrishnaBACKGROUND: 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.http://europepmc.org/articles/PMC2654506?pdf=render |
| spellingShingle | Maria Werner Szabolcs Semsey Kim Sneppen Sandeep Krishna Dynamics of uptake and metabolism of small molecules in cellular response systems. PLoS ONE |
| title | Dynamics of uptake and metabolism of small molecules in cellular response systems. |
| title_full | Dynamics of uptake and metabolism of small molecules in cellular response systems. |
| title_fullStr | Dynamics of uptake and metabolism of small molecules in cellular response systems. |
| title_full_unstemmed | Dynamics of uptake and metabolism of small molecules in cellular response systems. |
| title_short | Dynamics of uptake and metabolism of small molecules in cellular response systems. |
| title_sort | dynamics of uptake and metabolism of small molecules in cellular response systems |
| url | http://europepmc.org/articles/PMC2654506?pdf=render |
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