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Detecting breakdown points in metabolic networks

Paper ID Volume ID Publish Year Pages File Format Full-Text
15194 1389 2011 10 PDF Available
Title
Detecting breakdown points in metabolic networks
Abstract

BackgroundA complex network of biochemical reactions present in an organism generates various biological moieties necessary for its survival. It is seen that biological systems are robust to genetic and environmental changes at all levels of organization. Functions of various organisms are sustained against mutational changes by using alternative pathways. It is also seen that if any one of the paths for production of the same metabolite is hampered, an alternate path tries to overcome this defect and helps in combating the damage.MethodologyCertain physical, chemical or genetic change in any of the precursor substrate of a biochemical reaction may damage the production of the ultimate product. We employ a quantitative approach for simulating this phenomena of causing a physical change in the biochemical reactions by performing external perturbations to 12 metabolic pathways under carbohydrate metabolism in Saccharomyces cerevisae as well as 14 metabolic pathways under carbohydrate metabolism in Homo sapiens. Here, we investigate the relationship between structure and degree of compatibility of metabolites against external perturbations, i.e., robustness. Robustness can also be further used to identify the extent to which a metabolic pathway can resist a mutation event. Biological networks with a certain connectivity distribution may be very resilient to a particular attack but not to another. The goal of this work is to determine the exact boundary of network breakdown due to both random and targeted attack, thereby analyzing its robustness. We also find that compared to various non-standard models, metabolic networks are exceptionally robust. Here, we report the use of a ‘Resilience-based’ score for enumerating the concept of ‘network-breakdown’. We also use this approach for analyzing metabolite essentiality providing insight into cellular robustness that can be further used for future drug development.ResultsWe have investigated the behavior of metabolic pathways under carbohydrate metabolism in S. cerevisae and H. sapiens against random and targeted attack. Both random as well as targeted resilience were calculated by formulating a measure, that we termed as ‘Resilience score’. Datasets of metabolites were collected for 12 metabolic pathways belonging to carbohydrate metabolism in S. cerevisae and 14 metabolic pathways belonging to carbohydrate metabolism in H. sapiens from Kyoto Encyclopedia for Genes and Genomes (KEGG).

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► We employ a quantitative approach for simulating certain physical changes in some substrates. ► Robustness is studied. ► A random and targeted attack for substrate removal is employed. ► We also determine the exact boundary of network breakdown. ► The breakdown points and essential metabolites in pathway are found. ► We have showed that with increase in fitness of a metabolite, the resilience of the entire metabolic pathway increases.

Keywords
Graph theory; Breakdown; Perturbation; Resilience; Robustness
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Detecting breakdown points in metabolic networks
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Publisher
Database: Elsevier - ScienceDirect
Journal: Computational Biology and Chemistry - Volume 35, Issue 6, 14 December 2011, Pages 371–380
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us