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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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Detalles Bibliográficos
Autores principales: Parundekar, Akshay, Viswanathan, Ganesh A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087108/
https://www.ncbi.nlm.nih.gov/pubmed/33930059
http://dx.doi.org/10.1371/journal.pone.0250830
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author Parundekar, Akshay
Viswanathan, Ganesh A.
author_facet Parundekar, Akshay
Viswanathan, Ganesh A.
author_sort Parundekar, Akshay
collection PubMed
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.
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spelling pubmed-80871082021-05-06 Retroactivity induced operating regime transition in an enzymatic futile cycle Parundekar, Akshay Viswanathan, Ganesh A. PLoS One Research Article 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. Public Library of Science 2021-04-30 /pmc/articles/PMC8087108/ /pubmed/33930059 http://dx.doi.org/10.1371/journal.pone.0250830 Text en © 2021 Parundekar, Viswanathan https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Parundekar, Akshay
Viswanathan, Ganesh A.
Retroactivity induced operating regime transition in an enzymatic futile cycle
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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8087108/
https://www.ncbi.nlm.nih.gov/pubmed/33930059
http://dx.doi.org/10.1371/journal.pone.0250830
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