Directional regulation of cytosolic PEPCK catalysis is mediated by competitive binding of anions.
Biochem Biophys Res Commun
; 637: 218-223, 2022 12 31.
Article
en En
| MEDLINE
| ID: mdl-36403486
ABSTRACT
Phosphoenolpyruvate carboxykinase (PEPCK) is a well-characterized enzyme involved in primary glucose metabolism, responsible for catalyzing one of the key steps of gluconeogenesis. It is well demonstrated that PEPCK can efficiently catalyze the reversible interconversion of oxaloacetic acid (OAA) to phosphoenolpyruvate (PEP) in vitro, but the enzyme is typically ascribed a metabolic role that requires preferential catalysis in the direction of PEP synthesis in vivo. Here we present structural and functional data that demonstrate the preferential synthesis of PEP from OAA catalyzed by PEPCK in vivo is facilitated by anion-mediated enzyme inhibition that reduces enzyme activity more significantly in the direction of OAA synthesis than in the direction of PEP synthesis. From our studies we conclude that the specific binding of small, ubiquitous anions like chloride, present in millimolar concentrations under normal cellular conditions allows for metabolic control by restricting PEPCK to function in the direction of PEP synthesis.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fosfoenolpiruvato Carboxiquinasa (ATP)
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2022
Tipo del documento:
Article
País de afiliación:
Canadá