Pyruvate dehydrogenase kinase

Pyruvate dehydrogenase kinase (also pyruvate dehydrogenase complex kinase, PDC kinase, or PDK; ) is a kinase enzyme which acts to inactivate the enzyme pyruvate dehydrogenase by phosphorylating it using ATP.

PDK thus participates in the regulation of the pyruvate dehydrogenase complex of which pyruvate dehydrogenase is the first component. Both PDK and the pyruvate dehydrogenase complex are located in the mitochondrial matrix of eukaryotes. The complex acts to convert pyruvate (a product of glycolysis in the cytosol) to acetyl-coA, which is then oxidized in the mitochondria to produce energy, in the citric acid cycle. By downregulating the activity of this complex, PDK will decrease the oxidation of pyruvate in mitochondria and increase the conversion of pyruvate to lactate in the cytosol.

The opposite action of PDK, namely the dephosphorylation and activation of pyruvate dehydrogenase, is catalyzed by a phosphoprotein phosphatase called pyruvate dehydrogenase phosphatase.

(Pyruvate dehydrogenase kinase should not be confused with Phosphoinositide-dependent kinase-1, which is also sometimes known as "PDK1".)

Genes
PDK has four isozymes:
 * PDK1
 * PDK2
 * PDK3
 * PDK4

Regulation
Pyruvate dehydrogenase kinase is stimulated by ATP, NADH and acetyl-CoA.

It is inhibited by ADP, NAD+, CoA-SH and pyruvate.

Pyruvate dehydrogenase kinase is also inhibited by the drug dichloroacetate which has been tried as a treatment of certain metabolic diseases and is under investigation as a treatment of cancer.