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.

Normally, the active site of pyruvate dehydrogenase is in a stabilized and ordered conformation supported by a network of hydrogen bonds.

[6] This disrupts the hydrogen bond network and disorders the conformation of two phosphorylation loops.

These loops prevent the reductive acetylation step, thus halting overall activity of the enzyme.

[11] As a result, the pyruvate formed from glycolysis cannot be oxidized which leads to hyperglycaemia due to the fact that glucose in the blood cannot be used efficiently.

[12] PDK1 has shown to have increased activity in hypoxic cancer cells due to the presence of HIF-1.

PDK1 shunts pyruvate away from the citric acid cycle and keeps the hypoxic cell alive.

[17][18] In dogs, specifically Doberman Pinschers, a mutation in the PDK4 gene is associated with dilated cardiomyopathy (DCM).