Metabolomics

Dataset Information

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


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.

INSTRUMENT(S): Flow injection analysis MS - positive, Flow injection analysis MS - negative

SUBMITTER: Jordan Berg 

PROVIDER: MTBLS7237 | MetaboLights | 2023-08-07

REPOSITORIES: MetaboLights

Dataset's files

Source:
Action DRS
MTBLS7237 Other
FILES Other
a_MTBLS7237_FIA-MS_negative__metabolite_profiling.txt Txt
a_MTBLS7237_FIA-MS_positive__metabolite_profiling.txt Txt
files-all.json Other
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Publications

Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase.

Hicks Kevin G KG   Cluntun Ahmad A AA   Schubert Heidi L HL   Hackett Sean R SR   Berg Jordan A JA   Leonard Paul G PG   Ajalla Aleixo Mariana A MA   Zhou Youjia Y   Bott Alex J AJ   Salvatore Sonia R SR   Chang Fei F   Blevins Aubrie A   Barta Paige P   Tilley Samantha S   Leifer Aaron A   Guzman Andrea A   Arok Ajak A   Fogarty Sarah S   Winter Jacob M JM   Ahn Hee-Chul HC   Allen Karen N KN   Block Samuel S   Cardoso Iara A IA   Ding Jianping J   Dreveny Ingrid I   Gasper William C WC   Ho Quinn Q   Matsuura Atsushi A   Palladino Michael J MJ   Prajapati Sabin S   Sun Pengkai P   Tittmann Kai K   Tolan Dean R DR   Unterlass Judith J   VanDemark Andrew P AP   Vander Heiden Matthew G MG   Webb Bradley A BA   Yun Cai-Hong CH   Zhao Pengkai P   Wang Bei B   Schopfer Francisco J FJ   Hill Christopher P CP   Nonato Maria Cristina MC   Muller Florian L FL   Cox James E JE   Rutter Jared J  

Science (New York, N.Y.) 20230309 6636


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 regulator  ...[more]

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