Steady-State Metabolite Concentrations Reflect a Balance between Maximizing Enzyme Efficiency and Minimizing Total Metabolite Load
Steady-state metabolite concentrations in a microorganism typically span several orders of magnitude. The underlying principles governing these concentrations remain poorly understood. Here, we hypothesize that observed variation can be explained in terms of a compromise between factors that favor m...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784570/ |
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pubmed-3784570 |
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pubmed-37845702013-10-01 Steady-State Metabolite Concentrations Reflect a Balance between Maximizing Enzyme Efficiency and Minimizing Total Metabolite Load Tepper, Naama Noor, Elad Amador-Noguez, Daniel Haraldsdóttir, Hulda S. Milo, Ron Rabinowitz, Josh Liebermeister, Wolfram Shlomi, Tomer Research Article Steady-state metabolite concentrations in a microorganism typically span several orders of magnitude. The underlying principles governing these concentrations remain poorly understood. Here, we hypothesize that observed variation can be explained in terms of a compromise between factors that favor minimizing metabolite pool sizes (e.g. limited solvent capacity) and the need to effectively utilize existing enzymes. The latter requires adequate thermodynamic driving force in metabolic reactions so that forward flux substantially exceeds reverse flux. To test this hypothesis, we developed a method, metabolic tug-of-war (mTOW), which computes steady-state metabolite concentrations in microorganisms on a genome-scale. mTOW is shown to explain up to 55% of the observed variation in measured metabolite concentrations in E. coli and C. acetobutylicum across various growth media. Our approach, based strictly on first thermodynamic principles, is the first method that successfully predicts high-throughput metabolite concentration data in bacteria across conditions. Public Library of Science 2013-09-26 /pmc/articles/PMC3784570/ /pubmed/24086517 http://dx.doi.org/10.1371/journal.pone.0075370 Text en © 2013 Tepper et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Tepper, Naama Noor, Elad Amador-Noguez, Daniel Haraldsdóttir, Hulda S. Milo, Ron Rabinowitz, Josh Liebermeister, Wolfram Shlomi, Tomer |
| spellingShingle |
Tepper, Naama Noor, Elad Amador-Noguez, Daniel Haraldsdóttir, Hulda S. Milo, Ron Rabinowitz, Josh Liebermeister, Wolfram Shlomi, Tomer Steady-State Metabolite Concentrations Reflect a Balance between Maximizing Enzyme Efficiency and Minimizing Total Metabolite Load |
| author_facet |
Tepper, Naama Noor, Elad Amador-Noguez, Daniel Haraldsdóttir, Hulda S. Milo, Ron Rabinowitz, Josh Liebermeister, Wolfram Shlomi, Tomer |
| author_sort |
Tepper, Naama |
| title |
Steady-State Metabolite Concentrations Reflect a Balance between Maximizing Enzyme Efficiency and Minimizing Total Metabolite Load |
| title_short |
Steady-State Metabolite Concentrations Reflect a Balance between Maximizing Enzyme Efficiency and Minimizing Total Metabolite Load |
| title_full |
Steady-State Metabolite Concentrations Reflect a Balance between Maximizing Enzyme Efficiency and Minimizing Total Metabolite Load |
| title_fullStr |
Steady-State Metabolite Concentrations Reflect a Balance between Maximizing Enzyme Efficiency and Minimizing Total Metabolite Load |
| title_full_unstemmed |
Steady-State Metabolite Concentrations Reflect a Balance between Maximizing Enzyme Efficiency and Minimizing Total Metabolite Load |
| title_sort |
steady-state metabolite concentrations reflect a balance between maximizing enzyme efficiency and minimizing total metabolite load |
| description |
Steady-state metabolite concentrations in a microorganism typically span several orders of magnitude. The underlying principles governing these concentrations remain poorly understood. Here, we hypothesize that observed variation can be explained in terms of a compromise between factors that favor minimizing metabolite pool sizes (e.g. limited solvent capacity) and the need to effectively utilize existing enzymes. The latter requires adequate thermodynamic driving force in metabolic reactions so that forward flux substantially exceeds reverse flux. To test this hypothesis, we developed a method, metabolic tug-of-war (mTOW), which computes steady-state metabolite concentrations in microorganisms on a genome-scale. mTOW is shown to explain up to 55% of the observed variation in measured metabolite concentrations in E. coli and C. acetobutylicum across various growth media. Our approach, based strictly on first thermodynamic principles, is the first method that successfully predicts high-throughput metabolite concentration data in bacteria across conditions. |
| publisher |
Public Library of Science |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3784570/ |
| _version_ |
1612014678912794624 |