Skip to content Skip to navigation
University of Warwick
  • Study
  • |
  • Research
  • |
  • Business
  • |
  • Alumni
  • |
  • News
  • |
  • About

University of Warwick
Publications service & WRAP

Highlight your research

  • WRAP
    • Home
    • Search WRAP
    • Browse by Warwick Author
    • Browse WRAP by Year
    • Browse WRAP by Subject
    • Browse WRAP by Department
    • Browse WRAP by Funder
    • Browse Theses by Department
  • Publications Service
    • Home
    • Search Publications Service
    • Browse by Warwick Author
    • Browse Publications service by Year
    • Browse Publications service by Subject
    • Browse Publications service by Department
    • Browse Publications service by Funder
  • Help & Advice
University of Warwick

The Library

  • Login
  • Admin

The self-inhibitory nature of metabolic networks and its alleviation through compartmentalization

Tools
- Tools
+ Tools

Alam, Mohammad T., Olin-Sandoval, Viridiana, Stincone, Anna, Keller, Markus A., Zelezniak, Aleksej, Luisi, Ben and Ralser, Markus (2017) The self-inhibitory nature of metabolic networks and its alleviation through compartmentalization. Nature Communications, 8 . 16018. doi:10.1038/ncomms16018 ISSN 2041-1723.

[img]
Preview
PDF
WRAP-self-inhibitory-nature-metabolic-networks-Alam-2017.pdf - Published Version - Requires a PDF viewer.
Available under License Creative Commons Attribution 4.0.

Download (3527Kb) | Preview
Official URL: https://doi.org/10.1038/ncomms16018

Request Changes to record.

Abstract

Metabolites can inhibit the enzymes that generate them. To explore the general nature of metabolic self-inhibition, we surveyed enzymological data accrued from a century of experimentation and generated a genome-scale enzyme-inhibition network. Enzyme inhibition is often driven by essential metabolites, affects the majority of biochemical processes, and is executed by a structured network whose topological organization is reflecting chemical similarities that exist between metabolites. Most inhibitory interactions are competitive, emerge in the close neighbourhood of the inhibited enzymes, and result from structural similarities between substrate and inhibitors. Structural constraints also explain one-third of allosteric inhibitors, a finding rationalized by crystallographic analysis of allosterically inhibited L-lactate dehydrogenase. Our findings suggest that the primary cause of metabolic enzyme inhibition is not the evolution of regulatory metabolite–enzyme interactions, but a finite structural diversity prevalent within the metabolome. In eukaryotes, compartmentalization minimizes inevitable enzyme inhibition and alleviates constraints that self-inhibition places on metabolism.

Item Type: Journal Article
Subjects: Q Science > QP Physiology
Divisions: Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School > Biomedical Sciences > Microbiology & Infection
Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School
Library of Congress Subject Headings (LCSH): Metabolites, Enzymes, Metabolism
Journal or Publication Title: Nature Communications
Publisher: Nature Publishing Group
ISSN: 2041-1723
Official Date: 10 July 2017
Dates:
DateEvent
10 July 2017Published
23 May 2017Accepted
30 October 2016Submitted
Volume: 8
Article Number: 16018
DOI: 10.1038/ncomms16018
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Open Access (Creative Commons)
Date of first compliant deposit: 10 July 2017
Date of first compliant Open Access: 11 July 2017
Funder: Cancer Research UK (CRUK), Medical Research Council (Great Britain) (MRC), Wellcome Trust (London, England), European Research Council (ERC), Consejo nacional de ciencia y tecnología (México), European Molecular Biology Organization‏ (EMBO), European Commission (EC), Marie Skłodowska-Curie Actions, Fonds zur Förderung der Wissenschaftlichen Forschung (Austria) (FWF)
Grant number: FC001134 (CRUK), FC001134 (MRC), FC001134, 093735/Z/10/Z (Wellcome Trust (London, England)), Stg 260809 (ERC), 232510 (Consejo nacional de ciencia y tecnología (México)), ALTF-969 2014 (EMBO), TFCOFUND2013, GA-2013-609409 (EC), J3341 (FWF)
RIOXX Funder/Project Grant:
Project/Grant IDRIOXX Funder NameFunder ID
FC001134Cancer Research UK (CRUK)http://dx.doi.org/10.13039/501100000289
FC001134[MRC] Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
093735/Z/10/ZWellcome Trusthttp://dx.doi.org/10.13039/100010269
Stg 260809European Research Council (ERC)UNSPECIFIED
232510Consejo nacional de ciencia y tecnología (México)UNSPECIFIED
ALTF-969 2014European Molecular Biology Organization [EMBO]http://dx.doi.org/10.13039/100004410
GA-2013-609409European Commission (EC)UNSPECIFIED
TFCOFUND2013H2020 Marie Skłodowska-Curie Actionshttp://dx.doi.org/10.13039/100010665
J3341 (FWF) Fonds zur Förderung der Wissenschaftlichen Forschung (Austria) (FWF)http://dx.doi.org/10.13039/501100001711

Request changes or add full text files to a record

Repository staff actions (login required)

View Item View Item

Downloads

Downloads per month over past year

View more statistics

twitter

Email us: wrap@warwick.ac.uk
Contact Details
About Us