PDK1 (Pyruvate Dehydrogenase Kinase 1), also known as PDHK1, is a serine/threonine kinase. It plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. PDK1 plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress. Its activity can be enhanced by binding to the pyruvate dehydrogenase subunit DLAT, inhibited by AZD7545 (this compound interferes with DLAT binding and thereby inhibits kinase activity). Its activity can also be inhibited by dichloroacetate and radicicol.
