dorsal/arxiv
View SchemaThe Activity Reaction Core and Plasticity of Metabolic Networks
| Authors | E. Almaas, Z. N. Oltvai, A. -L. Barabasi |
|---|---|
| Categories | |
| ArXiv ID | q-bio/0601041 |
| URL | https://arxiv.org/abs/q-bio/0601041 |
| DOI | 10.1371/journal.pcbi.0010068 |
| Journal | PLoS Comput Biol 1, e68 (2005) |
Abstract
Understanding the system level adaptive changes taking place in an organism in response to variations in the environment is a key issue of contemporary biology. Current modeling approaches such as the constraint-based flux balance analyses (FBA) have proved highly successful in analyzing the capabilities of cellular metabolism, including its capacity to predict deletion phenotypes, the ability to calculate the relative flux values of metabolic reactions and the properties of alternate optimal growth states. Here, we use FBA to thoroughly assess the activity of the Escherichia coli, Helicobacter pylori, and Saccharomyces cerevisiae metabolism in 30,000 diverse simulated environments. We identify a set of metabolic reactions forming a connected metabolic core that carry non-zero fluxes under all growth conditions, and whose flux variations are highly correlated. Furthermore, we find that the enzymes catalyzing the core reactions display a considerably higher fraction of phenotypic essentiality and evolutionary conservation than those catalyzing non-core reactions. Cellular metabolism is characterized by a large number of species-specific conditionally-active reactions organized around an evolutionary conserved always active metabolic core. Finally, we find that most current antibiotics interfering with the bacterial metabolism target the core enzymes, indicating that our findings may have important implications for antimicrobial drug target discovery.
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"abstract": "Understanding the system level adaptive changes taking place in an organism\nin response to variations in the environment is a key issue of contemporary\nbiology. Current modeling approaches such as the constraint-based flux balance\nanalyses (FBA) have proved highly successful in analyzing the capabilities of\ncellular metabolism, including its capacity to predict deletion phenotypes, the\nability to calculate the relative flux values of metabolic reactions and the\nproperties of alternate optimal growth states. Here, we use FBA to thoroughly\nassess the activity of the Escherichia coli, Helicobacter pylori, and\nSaccharomyces cerevisiae metabolism in 30,000 diverse simulated environments.\nWe identify a set of metabolic reactions forming a connected metabolic core\nthat carry non-zero fluxes under all growth conditions, and whose flux\nvariations are highly correlated. Furthermore, we find that the enzymes\ncatalyzing the core reactions display a considerably higher fraction of\nphenotypic essentiality and evolutionary conservation than those catalyzing\nnon-core reactions. Cellular metabolism is characterized by a large number of\nspecies-specific conditionally-active reactions organized around an\nevolutionary conserved always active metabolic core. Finally, we find that most\ncurrent antibiotics interfering with the bacterial metabolism target the core\nenzymes, indicating that our findings may have important implications for\nantimicrobial drug target discovery.",
"arxiv_id": "q-bio/0601041",
"authors": [
"E. Almaas",
"Z. N. Oltvai",
"A. -L. Barabasi"
],
"categories": [
"q-bio.MN",
"cond-mat.dis-nn",
"q-bio.CB",
"q-bio.QM"
],
"doi": "10.1371/journal.pcbi.0010068",
"journal_ref": "PLoS Comput Biol 1, e68 (2005)",
"title": "The Activity Reaction Core and Plasticity of Metabolic Networks",
"url": "https://arxiv.org/abs/q-bio/0601041"
},
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