PCCA Gene: Propionyl-CoA Carboxylase Subunit Alpha - Function, Mutations, and Disease

The PCCA gene encodes the alpha subunit of propionyl-CoA carboxylase (PCC), a biotin-dependent mitochondrial enzyme that catalyzes the carboxylation of propionyl-CoA to D-methylmalonyl-CoA. This reaction is a critical step in the catabolism of branched-chain amino acids, odd-chain fatty acids, and cholesterol side chains. Mutations in PCCA cause propionic acidemia (PA), an autosomal recessive metabolic disorder characterized by accumulation of propionic acid and its derivatives, leading to metabolic acidosis, neurological impairment, and multi-organ dysfunction.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• Propanoate metabolism (KEGG: hsa00640)

• Valine

• leucine and isoleucine degradation (KEGG: hsa00280)

• Metabolic pathways (KEGG: hsa01100)

Propionyl-CoA carboxylase (PCC) is a heterododecamer composed of alpha (PCCA) and beta (PCCB) subunits. The alpha subunit contains the biotin carboxylase domain and the biotin carboxyl carrier domain, which binds biotin covalently. The enzyme requires biotin as a cofactor and ATP for activity. PCC catalyzes the carboxylation of propionyl-CoA to D-methylmalonyl-CoA, a key step in the catabolism of odd-chain fatty acids, branched-chain amino acids (isoleucine, valine, methionine, threonine), and cholesterol side chains. Deficiency leads to propionic acidemia.