Pyruvate carboxylase, mitochondrial

Pyruvate carboxylase (PC) is a mitochondrial enzyme that catalyzes the ATP-dependent carboxylation of biotin and subsequent transfer of the carboxyl group to pyruvate (UniProt: P11498). The enzyme plays a tissue-specific role in initiating gluconeogenesis in liver and kidney, and lipid synthesis in adipose tissue, liver, and brain. Mutations in PC cause pyruvate carboxylase deficiency, a rare metabolic disorder characterized by lactic acidosis, intellectual disability, and neonatal onset in severe cases (UniProt: P11498).

PC is relevant to Alzheimer's disease pathology, as the enzyme supports energy metabolism and biosynthetic pathways critical for neuronal function. According to quantitative proteomics analysis of post-mortem AD brain tissue, PC is downregulated in AD compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of −0.22 across tested subcellular fractions. This reduction may reflect compromised mitochondrial metabolic capacity in AD-affected neurons, consistent with the documented bioenergetic dysfunction in Alzheimer's pathogenesis.