PC Gene: Pyruvate Carboxylase – Function, Deficiency, and Disease

The PC gene encodes pyruvate carboxylase, a mitochondrial biotin-containing enzyme that catalyzes the carboxylation of pyruvate to oxaloacetate. This reaction is critical for gluconeogenesis, lipogenesis, and the replenishment of Krebs cycle intermediates (anaplerosis). PC is expressed primarily in liver, kidney, adipose tissue, and brain. Mutations in PC cause pyruvate carboxylase deficiency, a rare autosomal recessive metabolic disorder characterized by lactic acidosis, developmental delay, and failure to thrive.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Gluconeogenesis (Reactome: R-HSA-70263)

• Pyruvate metabolism (KEGG: hsa00620)

• Citrate cycle (TCA cycle) (KEGG: hsa00020)

• Biotin metabolism (KEGG: hsa00780)

Pyruvate carboxylase is a 130 kDa homotetrameric mitochondrial enzyme. Each subunit contains a biotin carboxylase domain, a carboxyltransferase domain, and a biotin carboxyl carrier protein domain. The enzyme requires biotin as a cofactor and ATP for activity. It catalyzes the ATP-dependent carboxylation of pyruvate to oxaloacetate, a key anaplerotic reaction. Defects in PC lead to severe metabolic disturbances, including lactic acidosis, hypoglycemia, and hyperammonemia.