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Directional regulation of cytosolic PEPCK catalysis is mediated by competitive binding of anions

DOI: 10.1016/j.bbrc.2022.11.025 DOI Help

Authors: Sarah Barwell (University of Waterloo) , Ramona Duman (Diamond Light Source) , Armin Wagner (Diamond Light Source) , Todd Holyoak (University of Waterloo)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Biochemical And Biophysical Research Communications , VOL 2

State: Published (Approved)
Published: November 2022
Diamond Proposal Number(s): 442

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.

Diamond Keywords: Enzymes

Subject Areas: Biology and Bio-materials, Chemistry

Instruments: I23-Long wavelength MX

Added On: 16/11/2022 08:32

Discipline Tags:

Biochemistry Chemistry Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX) Long Wavelength Crystallography