Pyruvate dehydrogenase lipoamide kinase isozyme 3, mitochondrial (PDK3)

Pyruvate dehydrogenase lipoamide kinase isozyme 3, mitochondrial (PDK3), is a mitochondrial enzyme encoded by the PDK3 gene in humans. It belongs to the family of pyruvate dehydrogenase kinases, which regulate the pyruvate dehydrogenase complex (PDC) by reversible phosphorylation, thereby controlling the conversion of pyruvate to acetyl-CoA and linking glycolysis to the TCA cycle. PDK3 is predominantly expressed in heart and skeletal muscle and is critical for cellular energy homeostasis. Dysregulation or overexpression of PDK3 is implicated in cancer, where it promotes the Warburg effect (aerobic glycolysis) and drug resistance. Several small molecule inhibitors, including myricetin, bagrosin, dehydrocholic acid, dichloroacetate, AZD7545, and radicicol, have demonstrated inhibitory effects on PDK3 through competitive interaction at key binding sites, offering therapeutic potential for cancer and other metabolic diseases. The structural mechanism of inhibition and activation is modulated via interaction with the pyruvate dehydrogenase complex lipoyl domains, influencing the enzyme’s conformation and activity.

Other names

Pyruvate dehydrogenase kinase isoform 3Pyruvate dehydrogenase kinase 3PDK3

Inhibition of kinase activity by competitive binding to ATP-binding site or lipoyl-binding pocket. Modulation of metabolic flux by restoration of pyruvate dehydrogenase complex (PDC) activity. Promotion of glucose oxidation and suppression of glycolysis.