Propionyl-CoA carboxylase beta subunit (PCCB) (PCCB)

Propionyl-CoA carboxylase beta subunit (PCCB) is a nuclear-encoded mitochondrial enzyme that functions as a critical component of the propionyl-CoA carboxylase (PCC) complex. This enzyme is a biotin-dependent carboxylase responsible for the conversion of propionyl-CoA into D-methylmalonyl-CoA, which subsequently enters the citric acid cycle (UniProt, 2024). This metabolic pathway is essential for the breakdown of specific branched-chain amino acids (isoleucine, valine, threonine, and methionine), odd-chain fatty acids, and the side chains of cholesterol (NIH, 2023). Mutations in the PCCB gene result in propionic acidemia, a severe autosomal recessive disorder characterized by the accumulation of toxic organic acids, leading to life-threatening episodes of metabolic acidosis and hyperammonemia (StatPearls, 2023). Current therapeutic research focuses on restoring PCC enzymatic function using novel mRNA-based therapies, such as mRNA-3927, which deliver transcripts for both PCCA and PCCB subunits to the liver to enable intracellular enzyme production (Moderna, 2024). Clinical management also involves dietary restriction of precursor amino acids and supplementation with L-carnitine or biotin to facilitate metabolic clearance and support residual enzyme activity (PubMed, 2022).

Other names

Propionyl-CoA carboxylase subunit beta, mitochondrialPCC-betaPropanoyl-CoA:carbon dioxide ligase (ADP-forming) subunit beta

Restoration of propionyl-CoA carboxylase enzymatic activity through mRNA-mediated protein expression or cofactor supplementation (Moderna, 2024; PubMed, 2022).