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 interconv

SUBMITTER: Hicks KG 

PROVIDER: S-EPMC10262665 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature