Quantifying global tolerance of biochemical systems: Design implications for moiety-transfer cycles

Pedro M B M Coelho, Armindo Salvador, Michael A. Savageau

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
JournalPLoS Computational Biology
Volume5
Issue number3
DOIs
StatePublished - Mar 2009

Fingerprint

System Design
Tolerance
tolerance
Systems analysis
Cycle
NADP
NADP (coenzyme)
normal values
Oxidation-Reduction
homeostasis
Reference Values
Phosphates
Homeostasis
erythrocytes
Erythrocytes
Robustness
Biological Sciences
prediction
Erythrocyte
organisms

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Ecology
  • Molecular Biology
  • Genetics
  • Ecology, Evolution, Behavior and Systematics
  • Modeling and Simulation
  • Computational Theory and Mathematics

Cite this

Quantifying global tolerance of biochemical systems : Design implications for moiety-transfer cycles. / Coelho, Pedro M B M; Salvador, Armindo; Savageau, Michael A.

In: PLoS Computational Biology, Vol. 5, No. 3, 03.2009.

Research output: Contribution to journalArticle

Coelho, Pedro M B M ; Salvador, Armindo ; Savageau, Michael A. / Quantifying global tolerance of biochemical systems : Design implications for moiety-transfer cycles. In: PLoS Computational Biology. 2009 ; Vol. 5, No. 3.
@article{f47bbee2193b4a0bada81d35d705a2b7,
title = "Quantifying global tolerance of biochemical systems: Design implications for moiety-transfer cycles",
abstract = "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.",
author = "Coelho, {Pedro M B M} and Armindo Salvador and Savageau, {Michael A.}",
year = "2009",
month = "3",
doi = "10.1371/journal.pcbi.1000319",
language = "English (US)",
volume = "5",
journal = "PLoS Computational Biology",
issn = "1553-734X",
publisher = "Public Library of Science",
number = "3",

}

TY - JOUR

T1 - Quantifying global tolerance of biochemical systems

T2 - Design implications for moiety-transfer cycles

AU - Coelho, Pedro M B M

AU - Salvador, Armindo

AU - Savageau, Michael A.

PY - 2009/3

Y1 - 2009/3

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=63549119474&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=63549119474&partnerID=8YFLogxK

U2 - 10.1371/journal.pcbi.1000319

DO - 10.1371/journal.pcbi.1000319

M3 - Article

C2 - 19300483

AN - SCOPUS:63549119474

VL - 5

JO - PLoS Computational Biology

JF - PLoS Computational Biology

SN - 1553-734X

IS - 3

ER -