Pyruvate dehydrogenase kinase isoform 2 (PDK2) (PDK2)

Pyruvate dehydrogenase kinase isoform 2 (PDK2) is a mitochondrial enzyme that plays a pivotal role in regulating glucose metabolism by controlling the activity of the pyruvate dehydrogenase complex (PDC) [UniProt: Q15119]. It functions by phosphorylating the E1 alpha subunit of the PDC, which inactivates the complex and prevents the conversion of pyruvate into acetyl-CoA, thus shifting metabolism away from glucose oxidation [PubMed: 11741314]. PDK2 is the most widely expressed isoform in human tissues, with high levels found in the liver, skeletal muscle, and heart [PubMed: 10617608]. In pathological states such as type 2 diabetes and cancer, PDK2 activity is often elevated, contributing to hyperglycemia and the Warburg effect, respectively [PubMed: 23161315]. Therapeutic targeting of PDK2 with inhibitors like dichloroacetate (DCA) or isoform-specific small molecules aims to reactivate the PDC to enhance glucose oxidation and reduce lactic acid production [PubMed: 25433554]. Such interventions are being explored for their potential to treat metabolic syndrome, heart failure, and various solid tumors [PubMed: 21859131].

Other names

Pyruvate dehydrogenase kinase 2PDHK2PDKII

Inhibition of PDK2 prevents the phosphorylation and inactivation of the pyruvate dehydrogenase complex (PDC), promoting the conversion of pyruvate to acetyl-CoA and increasing glucose oxidation.