PDK1

Description

The PDK1 (pyruvate dehydrogenase kinase 1) is a protein-coding gene located on chromosome 2.

PDK1, encoded by the PDK1 gene, is an isozyme of pyruvate dehydrogenase kinase (PDK). It is a mitochondrial enzyme involved in the regulation of carbohydrate fuel homeostasis in mammals. Pyruvate dehydrogenase (PDH) is a key component of a multienzyme complex in mitochondria that catalyzes the oxidative decarboxylation of pyruvate. PDK1 regulates PDH activity through phosphorylation/dephosphorylation. Phosphorylation of PDH by PDK1 leads to inactivation. The mature PDK1 protein has 407 amino acids and forms an open conformation with two polypeptide chains. The catalytic domain of PDK1 might exist independently in cells and is crucial for regulating the PDK1 substrate. Crystal structure studies suggest that the PIF-pocket is located within the catalytic domain. The PDH complex, due to its central role in metabolism, requires tight regulation.

PDK1 plays a crucial role in regulating glucose and fatty acid metabolism by phosphorylating PDHA1 and PDHA2 subunits of pyruvate dehydrogenase. This phosphorylation inhibits pyruvate dehydrogenase activity, thereby controlling the flow of metabolites through the tricarboxylic acid cycle. PDK1 also downregulates aerobic respiration and prevents the conversion of pyruvate into acetyl-coenzyme A. Furthermore, PDK1 is involved in cellular responses to low oxygen conditions (hypoxia) and is essential for cell proliferation under such conditions. PDK1 also protects cells from programmed cell death (apoptosis) in response to hypoxia and oxidative stress.

PDK1 is also known as -.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing