English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase

Hicks, K. G., Cluntun, A. A., Schubert, H. L., Hackett, S. R., Berg, J. A., Leonard, P. G., et al. (2023). Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase. Science, 379, 996-1003.

Item is

Files

hide Files
:
science.abm3452.pdf (Publisher version), 2MB
 
File Permalink:
-
Name:
science.abm3452.pdf
Description:
-
OA-Status:
Visibility:
Restricted ( Max Planck Society (every institute); )
MIME-Type / Checksum:
application/pdf
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

hide
 Creators:
Hicks, Kevin G., Author
Cluntun, Ahmad A., Author
Schubert, Heidi L., Author
Hackett, Sean R., Author
Berg, Jordan A., Author
Leonard, Paul G., Author
Ajalla Aleixo, Mariana A. , Author
Zhou, Youjia, Author
Bott, Alex J., Author
Salvatore, Sonia R., Author
Chang, Fei, Author
Blevins, Aubrie, Author
Barta, Paige, Author
Tilley, Samantha, Author
Leifer, Aaron, Author
Guzman, Andrea, Author
Arok, Ajak, Author
Fogarty, Sarah, Author
Winter, Jacob M., Author
Ahn, Hee-Chul, Author
more..
Affiliations:
1Department of Structural Dynamics, Max Planck Institute for Multidisciplinary Sciences, Max Planck Society, Göttingen, DE, ou_3350272              

Content

hide
Free keywords: -
 Abstract: Metabolic networks are interconnected and influence diverse cellular processes. The protein-metabolite interactions that mediate these networks are frequently low affinity and challenging to systematically discover. We developed mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically (MIDAS) to identify such interactions. Analysis of 33 enzymes from human carbohydrate metabolism identified 830 protein-metabolite interactions, including known regulators, substrates, and products as well as previously unreported interactions. We functionally validated a subset of interactions, including the isoform-specific inhibition of lactate dehydrogenase by long-chain acyl–coenzyme A. Cell treatment with fatty acids caused a loss of pyruvate-lactate interconversion dependent on lactate dehydrogenase isoform expression. These protein-metabolite interactions may contribute to the dynamic, tissue-specific metabolic flexibility that enables growth and survival in an ever-changing nutrient environment.

Details

hide
Language(s): eng - English
 Dates: 2023-03-10
 Publication Status: Issued
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: -
 Degree: -

Event

show

Legal Case

show

Project information

hide
Project name : This study received support from National Institutes of Health grants T32DK091317 (K.G.H.), T32DK007115 (K.G.H.), U54DK110858 (J.R.), R35GM131854 (J.R.), R01DK108859 (D.R.T.), R01GM103369 (A.P.V.), R35CA242379 (M.G.V.H.), R01CA201276 (M.G.V.H.), T32-GM007287 (S.B.), U54DK110858 (J.E.C.), R01HD04346 (M.J.P.), R01HD105311 (M.J.P.), R01 GM125944 (F.J.S.), R01 DK112854 (F.J.S.), F99CA253744 (J.A.B.), 5K00CA212445 (A.J.B.), T32DK091317 (A.L.), and F30CA243440 (J.M.W.); National Science Foundation DBI-1661375 and IIS-1513616 (B.W.); National Research Foundation of Korea grant 2021R1F1A1063558 (H.-C.A.); National Natural Science Foundation of China grant 32071207 (C.-H.Y.); German Research Foundation SFB860 (K.T.); Conselho Nacional de Desenvolvimento Científico e Tecnológico 308769/2019-8 (M.C.N.) and 154690/2018-0 (M.A.A.A.); Fundação de Amparo à Pesquisa do Estado de São Paulo 2008/08262-6 (M.C.N.); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior 88882.328384/2010-01 (M.A.A.A.); Calico LLC (J.R.); the Nora Eccles Treadwell Foundation (J.R. and C.P.H.); the Howard Hughes Medical Institute (J.R.); a Howard Hughes Faculty Scholars grant (M.G.V.H.); the Emerald Foundation (M.G.V.H.); the Lustgarten Foundation (M.G.V.H.); the Ludwig Center at MIT (M.G.V.H.); the MIT Center for Precision Cancer Medicine (M.G.V.H.); the University of Nottingham (I.D.); and the University of West Virginia (B.A.W.).
Grant ID : -
Funding program : -
Funding organization : -

Source 1

hide
Title: Science
  Abbreviation : Science
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: Washington, D.C. : American Association for the Advancement of Science
Pages: - Volume / Issue: 379 Sequence Number: - Start / End Page: 996 - 1003 Identifier: ISSN: 0036-8075
CoNE: https://pure.mpg.de/cone/journals/resource/991042748276600_1