pyruvaattikarboksylaasin

pyruvaattikarboksylaasin (pyruvate carboxylase; PC; EC 6.4.1.1) is a biotin-dependent enzyme that catalyzes the ATP‑dependent carboxylation of pyruvate to oxaloacetate, using carbon dioxide. It functions as an anaplerotic enzyme, replenishing oxaloacetate for the tricarboxylic acid cycle and providing carbon skeletons for gluconeogenesis and amino acid biosynthesis.

The enzyme is a multi-domain biotin‑containing complex. It contains a biotin carboxylase domain that activates CO2 with ATP to form carboxyphosphate, a biotin carboxyl carrier protein that holds biotin, and a carboxyltransferase domain that transfers the carboxyl group from carboxybiotin to pyruvate to yield oxaloacetate. In eukaryotes, the protein is typically located in mitochondria, whereas in some organisms or tissues, homologous enzymes may be found in plastids or cytosol.

Localization and function vary among organisms. In animals, PC resides mainly in mitochondria and contributes to maintaining the oxaloacetate pool for the TCA cycle and for hepatic gluconeogenesis during fasting. In plants and microorganisms, PC homologs exist with similar catalytic chemistry but different subcellular localizations, supporting metabolism such as respiration, biosynthesis, and carbon flux under various conditions.

Regulation of PC activity is primarily allosteric. In mammals, acetyl‑CoA is a key activator, linking fatty acid oxidation to anaplerotic flux toward gluconeogenesis. Genetic defects in pyruvate carboxylase cause pyruvate carboxylase deficiency, a rare autosomal recessive disorder characterized by lactic acidosis, hypoglycemia, and neurodevelopmental impairment, typically presenting in the neonatal period.