The PDHK Group
The PDHK group
The pyruvate dehydrogenase kinases are a small and ubiquitous group of aPKs which are known to be responsible for phosphorylating the E1 (pyruvate decarboxylase) subunit of the pyruvate dehydrogenase multienzyme complex. PDHK regulates the activity of this complex by an inactivating phosphorylation.
This complex is responsible for catalysing the oxidative decarboxylation of pyruvate, an important regulatory step in oxidative metabolism, and the phosphorylation of the E1 subunit results in a loss of pyruvate decarboxylase enzyme activity. PDHKs thus play a central role in controlling the balance between glucose and lipid oxidation according to substrate supply. The five PDHKs members identified in human each displays a distinct tissue-specific expression profile and present distinct regulatory properties.
It is thought that increasing glucose oxidation by inhibiting PDHK may be an effective mechanism to increase glucose utilization. Moreover, the increase of pyruvate oxidation may further contribute to the lowering of glucose levels by decreasing the supply of gluconeogenic substrates. This mechanism is currently being evaluated as a therapy for diabetes.
Mayers RM, Leighton B, Kilgour E. (2005) PDH kinase inhibitors: a novel therapy for Type II diabetes? Biochem Soc Trans. 33 367-70 PMID: 15787608