PDK4

This gene is a member of the PDK/BCKDK protein kinase family and encodes a mitochondrial protein with a histidine kinase domain. This protein is located in the matrix of the mitrochondria and inhibits the pyruvate dehydrogenase complex by phosphorylating one of its subunits, thereby contributing to the regulation of glucose metabolism. Expression of this gene is regulated by glucocorticoids, retinoic acid and insulin. [provided by RefSeq]

Full Name

pyruvate dehydrogenase kinase, isozyme 4

Function

Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Inhibition of pyruvate dehydrogenase decreases glucose utilization and increases fat metabolism in response to prolonged fasting and starvation. Plays an important role in maintaining normal blood glucose levels under starvation, and is involved in the insulin signaling cascade. Via its regulation of pyruvate dehydrogenase activity, plays an important role in maintaining normal blood pH and in preventing the accumulation of ketone bodies under starvation. In the fed state, mediates cellular responses to glucose levels and to a high-fat diet. Regulates both fatty acid oxidation and de novo fatty acid biosynthesis. Plays a role in the generation of reactive oxygen species. Protects detached epithelial cells against anoikis. Plays a role in cell proliferation via its role in regulating carbohydrate and fatty acid metabolism.

Biological Process

Cellular response to fatty acidManual Assertion Based On ExperimentIMP:UniProtKB
Cellular response to starvationManual Assertion Based On ExperimentIDA:UniProtKB
Glucose homeostasisISS:UniProtKB
Glucose metabolic processIEA:UniProtKB-KW
Insulin receptor signaling pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Negative regulation of anoikisManual Assertion Based On ExperimentIMP:UniProtKB
Protein phosphorylationManual Assertion Based On ExperimentIBA:GO_Central
Reactive oxygen species metabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of acetyl-CoA biosynthetic process from pyruvateManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of bone resorptionIEA:Ensembl
Regulation of cellular ketone metabolic processISS:UniProtKB
Regulation of fatty acid biosynthetic processManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of fatty acid oxidationISS:UniProtKB
Regulation of glucose metabolic processManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of pHISS:UniProtKB
Response to starvationISS:UniProtKB

Cellular Location

Mitochondrion matrix