Document Detail


The energy costs of insulators in biochemical networks.
MedLine Citation:
PMID:  23528097     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Complex networks of biochemical reactions, such as intracellular protein signaling pathways and genetic networks, are often conceptualized in terms of modules--semiindependent collections of components that perform a well-defined function and which may be incorporated in multiple pathways. However, due to sequestration of molecular messengers during interactions and other effects, collectively referred to as retroactivity, real biochemical systems do not exhibit perfect modularity. Biochemical signaling pathways can be insulated from impedance and competition effects, which inhibit modularity, through enzymatic futile cycles that consume energy, typically in the form of ATP. We hypothesize that better insulation necessarily requires higher energy consumption. We test this hypothesis through a combined theoretical and computational analysis of a simplified physical model of covalent cycles, using two innovative measures of insulation, as well as a possible new way to characterize optimal insulation through the balancing of these two measures in a Pareto sense. Our results indicate that indeed better insulation requires more energy. While insulation may facilitate evolution by enabling a modular plug-and-play interconnection architecture, allowing for the creation of new behaviors by adding targets to existing pathways, our work suggests that this potential benefit must be balanced against the metabolic costs of insulation necessarily incurred in not affecting the behavior of existing processes.
Authors:
John P Barton; Eduardo D Sontag
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2013-03-19
Journal Detail:
Title:  Biophysical journal     Volume:  104     ISSN:  1542-0086     ISO Abbreviation:  Biophys. J.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-26     Completed Date:  2013-09-05     Revised Date:  2014-03-24    
Medline Journal Info:
Nlm Unique ID:  0370626     Medline TA:  Biophys J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1380-90     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Energy Metabolism*
Models, Biological*
Signal Transduction*
Grant Support
ID/Acronym/Agency:
1R01GM086881/GM/NIGMS NIH HHS; 1R01GM100473/GM/NIGMS NIH HHS; R01 GM100473/GM/NIGMS NIH HHS
Comments/Corrections

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