Protein-metabolite interactomics of carbohydrate metabolism reveal regulation of lactate dehydrogenase.
Science
; 379(6636): 996-1003, 2023 03 10.
Article
en En
| MEDLINE
| ID: mdl-36893255
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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Metabolismo de los Hidratos de Carbono
/
Metaboloma
/
L-Lactato Deshidrogenasa
Límite:
Humans
Idioma:
En
Revista:
Science
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos