Propionyl-CoA carboxylase alpha chain, mitochondrial

Propionyl-CoA carboxylase alpha chain (PCCA) is the catalytic subunit of the mitochondrial biotin-dependent enzyme propionyl-CoA carboxylase, which catalyzes the carboxylation of propionyl-CoA to methylmalonyl-CoA (UniProt: P05165). The enzyme plays a key role in branched-chain amino acid catabolism and the oxidation of odd-chain fatty acids, metabolizing substrates including isoleucine, threonine, methionine, and valine. Mutations in PCCA cause propionic acidemia type I, a severe metabolic disorder characterized by developmental retardation and protein intolerance.

PCCA is upregulated in Alzheimer's disease brain tissue. Analysis of post-mortem AD brain compared to age-matched controls using TMT-labeled tandem mass spectrometry across four subcellular fractions revealed elevated PCCA levels with a mean log₂ fold-change of 0.60 (Chaparral AD proteomics). This upregulation suggests potential dysregulation of branched-chain amino acid metabolism or altered mitochondrial function in AD pathology, though the biological significance of this change requires further investigation.