Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10316/12296 https://doi.org/10.1371/journal.pcbi.1000319 |
Resumo: | Robustness of organisms is widely observed although difficult to precisely characterize. Performance can remain nearly constant within some neighborhood of the normal operating regime, leading to homeostasis, but then abruptly break down with pathological consequences beyond this neighborhood. Currently, there is no generic approach to identifying boundaries where local performance deteriorates abruptly, and this has hampered understanding of the molecular basis of biological robustness. Here we introduce a generic approach for characterizing boundaries between operational regimes based on the piecewise power-law representation of the system’s components. This conceptual framework allows us to define ‘‘global tolerance’’ as the ratio between the normal value of a parameter and the value at such a boundary. We illustrate the utility of this concept for a class of moiety-transfer cycles, which is a widespread module in biology. Our results show a region of ‘‘best’’ local performance surrounded by ‘‘poor’’ regions; also, selection for improved local performance often pushes the operating values away from regime boundaries, thus increasing global tolerance. These predictions agree with experimental data from the reduced nicotinamide adenine dinucleotide phosphate (NADPH) redox cycle of human erythrocytes |
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Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer CyclesRobustness of organisms is widely observed although difficult to precisely characterize. Performance can remain nearly constant within some neighborhood of the normal operating regime, leading to homeostasis, but then abruptly break down with pathological consequences beyond this neighborhood. Currently, there is no generic approach to identifying boundaries where local performance deteriorates abruptly, and this has hampered understanding of the molecular basis of biological robustness. Here we introduce a generic approach for characterizing boundaries between operational regimes based on the piecewise power-law representation of the system’s components. This conceptual framework allows us to define ‘‘global tolerance’’ as the ratio between the normal value of a parameter and the value at such a boundary. We illustrate the utility of this concept for a class of moiety-transfer cycles, which is a widespread module in biology. Our results show a region of ‘‘best’’ local performance surrounded by ‘‘poor’’ regions; also, selection for improved local performance often pushes the operating values away from regime boundaries, thus increasing global tolerance. These predictions agree with experimental data from the reduced nicotinamide adenine dinucleotide phosphate (NADPH) redox cycle of human erythrocytesThis work was supported in part by fellowships to PC (SFRH/BD/8304/2002) and AS (SFRH/BPD/9457/2002) from Fundacao para a Ciencia e Tecnologia, Portugal, and by grants to AS (PTDC/QUI/70523/2006) from Fundacao para a Ciencia e Tecnologia, Portugal, and to MAS (RO1-GM30054) from the US Public Health ServicePublic Library of Science2009-03-20info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/12296http://hdl.handle.net/10316/12296https://doi.org/10.1371/journal.pcbi.1000319engPLoS Computational Biology. 5:3 (2009)1553-734XCoelho, Pedro M. B. M.Salvador, ArmindoSavageau, Michael A.info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2020-11-06T17:00:14Zoai:estudogeral.uc.pt:10316/12296Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:01:41.094168Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles |
title |
Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles |
spellingShingle |
Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles Coelho, Pedro M. B. M. |
title_short |
Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles |
title_full |
Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles |
title_fullStr |
Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles |
title_full_unstemmed |
Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles |
title_sort |
Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles |
author |
Coelho, Pedro M. B. M. |
author_facet |
Coelho, Pedro M. B. M. Salvador, Armindo Savageau, Michael A. |
author_role |
author |
author2 |
Salvador, Armindo Savageau, Michael A. |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Coelho, Pedro M. B. M. Salvador, Armindo Savageau, Michael A. |
description |
Robustness of organisms is widely observed although difficult to precisely characterize. Performance can remain nearly constant within some neighborhood of the normal operating regime, leading to homeostasis, but then abruptly break down with pathological consequences beyond this neighborhood. Currently, there is no generic approach to identifying boundaries where local performance deteriorates abruptly, and this has hampered understanding of the molecular basis of biological robustness. Here we introduce a generic approach for characterizing boundaries between operational regimes based on the piecewise power-law representation of the system’s components. This conceptual framework allows us to define ‘‘global tolerance’’ as the ratio between the normal value of a parameter and the value at such a boundary. We illustrate the utility of this concept for a class of moiety-transfer cycles, which is a widespread module in biology. Our results show a region of ‘‘best’’ local performance surrounded by ‘‘poor’’ regions; also, selection for improved local performance often pushes the operating values away from regime boundaries, thus increasing global tolerance. These predictions agree with experimental data from the reduced nicotinamide adenine dinucleotide phosphate (NADPH) redox cycle of human erythrocytes |
publishDate |
2009 |
dc.date.none.fl_str_mv |
2009-03-20 |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10316/12296 http://hdl.handle.net/10316/12296 https://doi.org/10.1371/journal.pcbi.1000319 |
url |
http://hdl.handle.net/10316/12296 https://doi.org/10.1371/journal.pcbi.1000319 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
PLoS Computational Biology. 5:3 (2009) 1553-734X |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
Public Library of Science |
publisher.none.fl_str_mv |
Public Library of Science |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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1799133907457671168 |