¹³C-Labeled Diethyl Ketoglutarate Derivatives as Hyperpolarized Probes of 2-Ketoglutarate Dehydrogenase Activity.

ABSTRACT: The TCA cycle is a central metabolic pathway for energy production and biosynthesis. A major control point of metabolic flux through the cycle is the decarboxylation of 2-ketoglutarate by the TCA cycle enzyme 2-ketoglutarate dehydrogenase (2-KGDH). In this project, we developed ¹³C labeled 2-ketoglutarate derivatives to monitor 2-KGDH activity in vivo. ¹³C NMR analysis of liver extracts revealed that uniformly ¹³C labeled 2-ketogutarate, in its cell permeable ester form, was rapidly taken up and hydrolyzed in liver and underwent extensive metabolism to produce labeled glutamate, succinate, lactate and other metabolites. Diethyl [1,2-¹³C₂]-2-ketoglutarate was successfully polarized by dynamic nuclear polarization and within seconds afte

SUBMITTER: Singh J 

PROVIDER: S-EPMC9165698 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature