Pyruvate dehydrogenase lipoamide kinase isozyme 1, mitochondrial (PDK1)

Pyruvate dehydrogenase lipoamide kinase isozyme 1, mitochondrial (PDK1) is an enzyme encoded by the PDK1 gene in humans, and is a mitochondrial protein kinase that phosphorylates and inactivates the E1 subunit of the pyruvate dehydrogenase complex (PDH)[1][2][4]. This phosphorylation inhibits the conversion of pyruvate to acetyl-CoA, reducing TCA cycle activity and aerobic respiration, thereby regulating the metabolic flux between glycolysis and oxidative phosphorylation[1][2][4][5]. PDK1 plays a critical role in metabolic regulation, cellular response to hypoxia, and cell proliferation under low-oxygen conditions. Pathologically, overactivity of PDK1 is implicated in the metabolic adaptations seen in cancer and diabetes[4][5]. Drugs such as dichloroacetic acid and AZD7545 can inhibit PDK1 activity, representing potential therapeutic avenues[1].

Other names

Pyruvate dehydrogenase kinase 1PDH kinase 1PDHK1Pyruvate dehydrogenase kinase isoform 12.7.11.2 (EC number)

Inhibition of pyruvate dehydrogenase kinase 1 leads to increased activity of the pyruvate dehydrogenase complex, enhancing acetyl-CoA formation from pyruvate and increasing flux through the TCA cycle[1][2][4]. Small molecule inhibitors (like DCA) bind to PDK1, induce conformational changes, and inactivate its kinase activity[1].