Kinase Family PDHK

Kinase Classification: Group Atypical: Family PDHK (previously known as PDK)

The Pyruvate Dehydrogenase Kinases are mitochondrial metabolic regulators. They phosphorylate and inactivate the alpha (or E1) subunits of pyruvate dehydrogenase, and so inhibit the citric acid (TCA, Krebs) cycle. They are related to the histidine kinases found in bacteria and eukaryotes, but phosphorylate on serine rather than histidine/aspartate.

Evolution

PDHK is found in fungi and animals. It has two subfamilies: the 'regular' PDHK, and BCKDK (Branched-Chain Ketoacid Dehydrogenase Kinase), though some organisms have members that are difficult to classify.

Function

PDHK has only one known substrate, the E1 (or alpha) subunits of Pyruvate Dehydrogenase (PDH). PDH transforms pyruvate (from glycolysis) into acetyl coA (which feeds the citric acid cycle in the mitochondrion), so phosphorylation of PDH blocks the citric acid cycle and results in pyruvate being transformed to lactate instead.

BCKDK inactivates BCKDH, by phosphorylation of the homologous E1 subunit. The BCKDH complex is biochemically similar to the PDH complex, but is involved in the degradation of branched-chain amino acids (valine, leucine, isoleucine).