Pyruvate dehydrogenase phosphatase catalytic subunit 1 (PDP1)

Pyruvate dehydrogenase phosphatase catalytic subunit 1 (PDP1) is a mitochondrial enzyme of the protein phosphatase 2C family that catalyzes the Mg2+/Mn2+-dependent dephosphorylation and activation of the E1 subunit of the pyruvate dehydrogenase complex (PDC). This reactivates the complex, facilitating the conversion of pyruvate to acetyl-CoA—a critical link between glycolysis and the tricarboxylic acid cycle, essential for cellular energy production. PDP1 activity is regulated by calcium and is predominantly expressed in skeletal muscle, with mutations leading to rare, autosomal recessive disorders characterized by lactic acidosis, developmental delay, and neurological symptoms. PDP1 is a validated enzyme target, but no selective pharmacological modulators are yet in approved therapeutic use[1][2][3][7].

Other names

Pyruvate dehydrogenase [acetyl-transferring]-phosphatase 1, mitochondrialPDPPPM2CPPM2APDHPDPCProtein phosphatase 2C, magnesium-dependent, catalytic subunitProtein phosphatase, Mg2+/Mn2+ dependent 2APyruvate dehydrogenase (Lipoamide) phosphatase-phosphatase

Enhancement or inhibition of PDP1 would regulate the dephosphorylation and activation status of the pyruvate dehydrogenase complex, modulating cellular acetyl-CoA production and mitochondrial energy output[2][3][7]