VER-246608

Pyruvate dehydrogenase kinase (PDK) has 4 isoforms: PDK1, PDK2, PDK3, and PDK4. PDKs regulate the metabolic link between glycolysis and the TCA (tricarboxylic acid) cycle. PDK activity is inhibited by phosphorylation of serine residues on PDH (pyruvate dehydrogenase) . Each isoform is expressed differently across different tissues types, and their activity is affected by cell energy availability and insulin levels. PDK1-3 have been found to act as oncogenes, their expression linked to higher rates of tumor metastasis and proliferation. However, upregulation of PDK4 may act as a tumor suppressor in lung cancer and hepatocellular carcinoma (HCCa) cells. PDK inhibitors have been developed to target diabetes, cancer, and heart disease.