Quantifying Global Tolerance of Biochemical Systems: Design Implications for Moiety-Transfer Cycles
| Autor: | Pedro M. B. M. Coelho, Michael A. Savageau, Armindo Salvador |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
Reduced nicotinamide-adenine dinucleotide
Proteome Redox cycle Biology Models Biological Computational Biology/Metabolic Networks 03 medical and health sciences Cellular and Molecular Neuroscience Genetics Computer Simulation Hematology/Disorders of Red Cell Metabolism lcsh:QH301-705.5 Molecular Biology Ecology Evolution Behavior and Systematics Normal range 030304 developmental biology 0303 health sciences Computational Biology/Systems Biology Biochemistry/Theory and Simulation Ecology 030302 biochemistry & molecular biology Robustness (evolution) lcsh:Biology (General) Gene Expression Regulation Computational Theory and Mathematics Modeling and Simulation Piecewise Systems design Human erythrocytes Biological system Mathematics Algorithms Research Article Signal Transduction |
| Zdroj: | PLoS Computational Biology PLoS Computational Biology, Vol 5, Iss 3, p e1000319 (2009) Repositório Científico de Acesso Aberto de Portugal Repositório Científico de Acesso Aberto de Portugal (RCAAP) instacron:RCAAP |
| ISSN: | 1553-7358 |
| DOI: | 10.1371/journal.pcbi.1000319 |
| Popis: | 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 Summary The ability of organisms to survive under a multitude of conditions is readily apparent. This robustness in performance is difficult to precisely characterize and quantify. At a biochemical level, it leads to physiological behavior when the parameters of the system remain within some neighborhood of their normal values. However, this behavior can change abruptly, often becoming pathological, as the boundary of the neighborhood is crossed. Currently, there is no generic approach to identifying and characterizing such boundaries. In this paper, we address the problem by introducing a method that involves quantitative concepts for boundaries between regions and “global tolerance”. To illustrate the power of these concepts, we analyzed a large class of biological modules called moiety-transfer cycles and characterized the specific case of the NADPH redox cycle in human erythrocytes, which is involved in conferring resistance to malaria. Our results show that the wild-type system operates well within a region of “best” local performance that is surrounded by “poor” regions. |
| Databáze: | OpenAIRE |
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