Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Co-substrate pools can constrain and regulate pathway fluxes in cell metabolism

Robert West, Hadrien Delattre, Elad Noor, Elisenda Feliu, View ORCID ProfileOrkun S Soyer
doi: https://doi.org/10.1101/2022.09.05.506656
Robert West
1School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hadrien Delattre
1School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elad Noor
2Department of Plant and Environmental Sciences, Weizmann Institute of Science, Rehovot 7610001, Israel
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Elisenda Feliu
3Department of Mathematics, University of Copenhagen, Copenhagen, Denmark
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: o.soyer@warwick.ac.uk efeliu@math.ku.dk
Orkun S Soyer
1School of Life Sciences, University of Warwick, Coventry, CV4 7AL, UK
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Orkun S Soyer
  • For correspondence: o.soyer@warwick.ac.uk efeliu@math.ku.dk
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Cycling of co-substrates, whereby a metabolite is converted among alternate forms via different reactions, is ubiquitous in metabolism. Several cycled co-substrates are well known as energy and electron carriers (e.g. ATP and NAD(P)H), but there are also other metabolites that act as cycled co-substrates in different parts of central metabolism. Here, we develop a mathematical framework to analyse the effect of co-substrate cycling on metabolic flux. In the cases of a single reaction and linear pathways, we find that co-substrate cycling imposes an additional flux limit on a reaction, distinct to the limit imposed by the kinetics of the primary enzyme catalysing that reaction. Using analytical methods, we show that this additional limit is a function of the total pool size and turnover rate of the cycled co-substrate. Expanding from this insight and using simulations, we show that regulation of co-substrate pool size can allow regulation of flux dynamics in branched and coupled pathways. To support theses theoretical insights, we analysed existing flux measurements and enzyme levels from the central carbon metabolism and identified several reactions that could be limited by co-substrate cycling. We discuss how the limitations imposed by co-substrate cycling provide experimentally testable hypotheses on specific metabolic phenotypes. We conclude that measuring and controlling co-substrate pools is crucial for understanding and engineering the dynamics of metabolism.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • Funding key: This project is funded by the Biotechnology and Biological Sciences Research Council (BBSRC) (grant BB/T010150/1). EF acknowledges funding from the Novo Nordisk Foundation (grant NNF18OC0052483), while OSS acknowledges support from the Gordon and Betty Moore Foundation (grant https://doi.org/10.37807/GBMF9200).

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
Back to top
PreviousNext
Posted September 06, 2022.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Co-substrate pools can constrain and regulate pathway fluxes in cell metabolism
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Co-substrate pools can constrain and regulate pathway fluxes in cell metabolism
Robert West, Hadrien Delattre, Elad Noor, Elisenda Feliu, Orkun S Soyer
bioRxiv 2022.09.05.506656; doi: https://doi.org/10.1101/2022.09.05.506656
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Co-substrate pools can constrain and regulate pathway fluxes in cell metabolism
Robert West, Hadrien Delattre, Elad Noor, Elisenda Feliu, Orkun S Soyer
bioRxiv 2022.09.05.506656; doi: https://doi.org/10.1101/2022.09.05.506656

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Systems Biology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4119)
  • Biochemistry (8828)
  • Bioengineering (6532)
  • Bioinformatics (23484)
  • Biophysics (11805)
  • Cancer Biology (9223)
  • Cell Biology (13336)
  • Clinical Trials (138)
  • Developmental Biology (7442)
  • Ecology (11425)
  • Epidemiology (2066)
  • Evolutionary Biology (15173)
  • Genetics (10453)
  • Genomics (14056)
  • Immunology (9187)
  • Microbiology (22199)
  • Molecular Biology (8823)
  • Neuroscience (47626)
  • Paleontology (351)
  • Pathology (1431)
  • Pharmacology and Toxicology (2493)
  • Physiology (3736)
  • Plant Biology (8090)
  • Scientific Communication and Education (1438)
  • Synthetic Biology (2224)
  • Systems Biology (6042)
  • Zoology (1254)