Retroactivity induced operating regime transition in an enzymatic futile cycle.
Activated phosphorylation-dephosphorylation biochemical reaction cycles are a class of enzymatic futile cycles. A futile cycle such as a single MAPK cascade governed by two underlying enzymatic reactions permits Hyperbolic (H), Signal transducing (ST), Threshold-hyperbolic (TH) and Ultrasensitive (U...
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Public Library of Science (PLoS)
2021-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0250830&type=printable |
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| author | Akshay Parundekar Ganesh A Viswanathan |
| author_facet | Akshay Parundekar Ganesh A Viswanathan |
| author_sort | Akshay Parundekar |
| collection | DOAJ |
| description | Activated phosphorylation-dephosphorylation biochemical reaction cycles are a class of enzymatic futile cycles. A futile cycle such as a single MAPK cascade governed by two underlying enzymatic reactions permits Hyperbolic (H), Signal transducing (ST), Threshold-hyperbolic (TH) and Ultrasensitive (U) operating regimes that characterize input-output behaviour. Retroactive signalling caused by load due to sequestration of phosphorylated or unphosphorylated form of the substrate in a single enzymatic cascade without explicit feedback can introduce two-way communication, a feature not possible otherwise. We systematically characterize the operating regimes of a futile cycle subject to retroactivity in either of the substrate forms. We demonstrate that increasing retroactivity strength, which quantifies the downstream load, can trigger five possible regime transitions. Retroactivity strength is a reflection of the fraction of the substrate sequestered by its downstream target. Remarkably, the minimum required retroactivity strength to evidence any sequestration triggered regime transition demands 23% of the substrate bound to its downstream target. This minimum retroactivity strength corresponds to the transition of the dose-response curve from ST to H regime. We show that modulation of the saturation and unsaturation levels of the enzymatic reactions by retroactivity is the fundamental mechanism governing operating regime transition. |
| format | Article |
| id | doaj-art-92d97ad616594b4da574b7f8ebb60a52 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2021-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-92d97ad616594b4da574b7f8ebb60a522025-08-20T02:54:30ZengPublic Library of Science (PLoS)PLoS ONE1932-62032021-01-01164e025083010.1371/journal.pone.0250830Retroactivity induced operating regime transition in an enzymatic futile cycle.Akshay ParundekarGanesh A ViswanathanActivated phosphorylation-dephosphorylation biochemical reaction cycles are a class of enzymatic futile cycles. A futile cycle such as a single MAPK cascade governed by two underlying enzymatic reactions permits Hyperbolic (H), Signal transducing (ST), Threshold-hyperbolic (TH) and Ultrasensitive (U) operating regimes that characterize input-output behaviour. Retroactive signalling caused by load due to sequestration of phosphorylated or unphosphorylated form of the substrate in a single enzymatic cascade without explicit feedback can introduce two-way communication, a feature not possible otherwise. We systematically characterize the operating regimes of a futile cycle subject to retroactivity in either of the substrate forms. We demonstrate that increasing retroactivity strength, which quantifies the downstream load, can trigger five possible regime transitions. Retroactivity strength is a reflection of the fraction of the substrate sequestered by its downstream target. Remarkably, the minimum required retroactivity strength to evidence any sequestration triggered regime transition demands 23% of the substrate bound to its downstream target. This minimum retroactivity strength corresponds to the transition of the dose-response curve from ST to H regime. We show that modulation of the saturation and unsaturation levels of the enzymatic reactions by retroactivity is the fundamental mechanism governing operating regime transition.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0250830&type=printable |
| spellingShingle | Akshay Parundekar Ganesh A Viswanathan Retroactivity induced operating regime transition in an enzymatic futile cycle. PLoS ONE |
| title | Retroactivity induced operating regime transition in an enzymatic futile cycle. |
| title_full | Retroactivity induced operating regime transition in an enzymatic futile cycle. |
| title_fullStr | Retroactivity induced operating regime transition in an enzymatic futile cycle. |
| title_full_unstemmed | Retroactivity induced operating regime transition in an enzymatic futile cycle. |
| title_short | Retroactivity induced operating regime transition in an enzymatic futile cycle. |
| title_sort | retroactivity induced operating regime transition in an enzymatic futile cycle |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0250830&type=printable |
| work_keys_str_mv | AT akshayparundekar retroactivityinducedoperatingregimetransitioninanenzymaticfutilecycle AT ganeshaviswanathan retroactivityinducedoperatingregimetransitioninanenzymaticfutilecycle |