Recombinant human PDK3 protein

Supplementary information

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

PDK3 also known as Pyruvate Dehydrogenase Kinase Isozyme 3 plays a mechanical role in regulating the activity of the pyruvate dehydrogenase (PDH) complex by phosphorylation. It phosphorylates the E1 component of the PDH complex which inhibits PDH activity and reduces the conversion of pyruvate to acetyl-CoA. PDK3 has a molecular mass of approximately 47 kDa and is mainly expressed in skeletal muscle and heart tissues.

Biological function summary

This kinase functions as an important modulator of glucose metabolism. PDK3 acts within the mitochondrial matrix interacting with its substrate as part of the larger PDH complex. Through its regulatory influence PDK3 helps maintain cellular energy homeostasis by balancing usage of carbohydrates and lipids depending on metabolic demands and availability of nutrients.

Pathways

PDK3 integrates into critical energy metabolism networks such as the tricarboxylic acid (TCA) cycle and the gluconeogenesis pathway. It regulates the PDH complex by inhibition impacting the flow of carbon through these pathways. PDK3's activity relates closely with other PDK isoforms such as PDK1 PDK2 and PDK4 which also modulate PDH complex function depending on tissue-specific and metabolic conditions.

PDK3 holds significance in diabetes and cancer. In type 2 diabetes PDK3's inhibition of PDH can contribute to impaired glucose oxidation leading to elevated blood glucose levels. In cancer the upregulation of PDK3 may support the metabolic switch to aerobic glycolysis a hallmark of many tumors commonly known as the Warburg effect. The activity of PDK3 in these conditions connects with lactate dehydrogenase (LDH) in cancer as both enzymes participate in metabolic reprogramming favoring lactate production.