Anti-PDK1 + PDK2 + PDK4 antibody [EPR19727]

Supplementary info

This supplementary information is collated from multiple sources and compiled automatically.

Activity summary

The protein targets PDK1 PDK2 and PDK4 short for pyruvate dehydrogenase kinase 1 2 and 4 are enzymes that regulate the activity of the pyruvate dehydrogenase complex (PDC) by phosphorylation inhibiting its enzymatic function. PDK1 has a mass of approximately 49 kDa PDK2 about 46 kDa and PDK4 around 48 kDa. These kinases are expressed in various tissues with PDK2 showing expression in heart pancreas and kidney while PDK4 expression is more observed in skeletal muscle and liver. PDK1 is ubiquitously expressed.

Biological function summary

These kinases play key roles in controlling cellular metabolism by inhibiting the conversion of pyruvate to acetyl-CoA a critical step linking glycolysis to the tricarboxylic acid (TCA) cycle. Acting separately but in functionally similar ways to each other PDK1 PDK2 and PDK4 help regulate energy homeostasis and preserve glucose during starvation or limited oxygen supply. These kinases are also part of larger complexes and interact with the pyruvate dehydrogenase complex and molecules like NADH and acetyl-CoA that further modulate their activity.

Pathways

PDK1 PDK2 and PDK4 are integral to the metabolic pathways that control glucose metabolism and TCA cycle by modulating pyruvate dehydrogenase complex activity. These kinases interact with signaling pathways in response to hormonal and nutrient signals adapting the body's energy metabolism under varying conditions. The insulin signaling pathway and hypoxia-inducible factor (HIF) pathway significantly influence their activity. Insulin signaling decreases the activity of PDK leading to an increase in pyruvate dehydrogenase activity and therefore in glucose oxidation. Meanwhile HIF pathway activation in low oxygen conditions upregulates PDKs to promote anaerobic metabolism.

Associated diseases and disorders

The dysregulation of PDK1 PDK2 and PDK4 is linked to metabolic conditions such as diabetes and cancer. In diabetes an upregulation of PDK activity can lead to reduced glucose oxidation and increased blood glucose levels often connected to insulin resistance. PDKs suppress he activity of the pyruvate dehydrogenase complex leading to altered energy metabolism that is a hallmark in many cancers. Proteins such as insulin receptor substrate (IRS) in diabetes and hypoxia-inducible factor-1α (HIF-1α) in cancer are partners that link PDK activity to these disease states as they modulate PDK expression and activity in response to metabolic demands.