The DOI matches its Crossref record; 50 of the 51 references it cites were found in a registry or an index.
Stochastic fluctuations in metabolic pathways
Open accessAbstract
Fluctuations in the abundance of molecules in the living cell may affect its growth and well being. For regulatory molecules (e.g., signaling proteins or transcription factors), fluctuations in their expression can affect the levels of downstream targets in a network. Here, we develop an analytic framework to investigate the phenomenon of noise correlation in molecular networks. Specifically, we focus on the metabolic network, which is highly interlinked, and noise properties may constrain its structure and function. Motivated by the analogy between the dynamics of a linear metabolic pathway and that of the exactly soluble linear queuing network or, alternatively, a mass transfer system, we derive a plethora of results concerning fluctuations in the abundance of intermediate metabolites in various common motifs of the metabolic network. For all but one case examined, we find the steady-state fluctuation in different nodes of the pathways to be effectively uncorrelated. Consequently, fluctuations in enzyme levels only affect local properties and do not propagate elsewhere into metabolic networks, and intermediate metabolites can be freely shared by different reactions. Our approach may be applicable to study metabolic networks with more complex topologies or protein signaling networks that are governed by similar biochemical reactions. Possible implications for bioinformatic analysis of metabolomic data are discussed.
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“Actually, stochasticity rules all living cells through fluctuations in gene expression, molecular interactions, and metabolic fluxes, even systems governed by deterministic laws, such as monogenic genetics [131,132,133,134].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [134]
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“Beyond identifiable causes, a large part of phenotype variability across patients with the same ABCD1 genotype may “simply” be due to stochasticity, a factor hitherto considered “noise” by Cartesian researchers.”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [134]
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Citations
Cites
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Stochasticity in gene expression: from theories to phenotypes
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Cited by
Sorted by citations
Tsimring, L. S. (2014) · Reports on Progress in Physics · doi:10.1088/0034-4885/77/2/026601 · Cited by 455
Stochasticity of metabolism and growth at the single-cell level
Kiviet, D. J., Nghe, P., Walker, N., Boulineau, S., Šunderlíková, V., & Tans, S. J. (2014) · Nature · doi:10.1038/nature13582 · Cited by 419
Exploiting nongenetic cell-to-cell variation for enhanced biosynthesis
Xiao, Y., Bowen, C. H., Liu, D., & Zhang, F. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2046 · Cited by 237
Product-Form Stationary Distributions for Deficiency Zero Chemical Reaction Networks
Anderson, D. F., Crăciun, G., & Kurtz, T. G. (2010) · Bulletin of Mathematical Biology · doi:10.1007/s11538-010-9517-4 · Cited by 220
From the stochasticity of molecular processes to the variability of synaptic transmission
Ribrault, C., Sekimoto, K., & Triller, A. (2011) · Nature Reviews Neuroscience · doi:10.1038/nrn3025 · Cited by 198
Metadata
- Authors
- Levine, E., & Hwa, T.
- Affiliations
- University of California San Diego (US)
- Center for Theoretical Biological Physics and Department of Physics, University of California at San Diego, La Jolla, CA 92093-0374
- ORCID
- Levine, Erel
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2007-05-29
- Volume
- 104
- Issue
- 22
- Pages
- 9224-9229
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC1890476
- OpenAlex
- W1979682650
- Cited by
- 132
- References
- 51
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 7 · 2023: 7 · 2022: 6 · 2021: 7 · 2020: 9 · 2019: 5 · 2018: 6 · 2017: 8 · 2016: 9 · 2015: 4 · 2014: 10 · 2013: 4 · 2012: 10
- FWCI
- 3.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- arXiv (Cornell University) (submittedVersion)
- arXiv (Cornell University)
- Funders
- National Science Foundation (0211308, 0225630, 0216576)
- Division of Materials Research
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gene Regulatory Network Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial Metabolic Engineering and Bioproduction
- Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › stochastic dynamics and bifurcation
- Keywords
- stochastic fluctuations, metabolic networks, noise correlation, metabolic intermediates, enzyme levels, steady-state fluctuations, metabolomics, protein signaling networks
- MeSH terms
- Probability, Proteins, Substrate Specificity, Metabolic Networks and Pathways
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