Pcca, the gene encoding the alpha subunit of propionyl-CoA carboxylase, is crucial for the proper function of the propionyl-CoA carboxylase enzyme. This enzyme plays a key role in the metabolism of odd-chain fatty acids, some amino acids, and cholesterol side-chains by catalyzing the carboxylation of propionyl-CoA to methylmalonyl-CoA. Dysfunction in this pathway can lead to metabolic disorders [1].

A study found that the PCCA c.1285-1416A>G variation activates a pseudoexon, causing severe propionic acidemia due to deficiency of the propionyl-CoA carboxylase enzyme. By blocking the region of regulation with splice-switching antisense oligonucleotides, normal splicing was restored, and enzyme activity was rescued in patient fibroblasts and a CRISPR-created cellular model. Interestingly, blocking the inclusion of the non-activated wild-type pseudoexon could increase both PCCA and PCCB protein levels, enhancing the activity of the heterododecameric enzyme, even in fibroblasts with PCCB missense variants. This presents a potential treatment strategy for propionic acidemia [1].

In conclusion, Pcca is essential for the normal metabolism of certain nutrients through the proper function of the propionyl-CoA carboxylase enzyme. The study of Pcca, especially through understanding the effects of specific genetic variations like c.1285-1416A>G, provides insights into the pathogenesis of propionic acidemia and potential treatment approaches for this metabolic disorder.