PCCA gene
propionyl-CoA carboxylase alpha subunit
The PCCA gene provides instructions for making part of an enzyme called propionyl-CoA carboxylase, specifically, the alpha subunit of this enzyme. Six alpha subunits come together with six beta subunits (produced from the PCCB gene) to form a functioning enzyme. The alpha subunit also includes a region for binding to the B vitamin biotin.
Propionyl-CoA carboxylase plays a role in the normal processing of proteins. It is responsible for a particular step in the breakdown of several protein building blocks (amino acids) called isoleucine, methionine, threonine, and valine. Propionyl-CoA carboxylase also helps break down certain types of lipids (fats) and cholesterol. First, several chemical reactions convert the amino acids, lipids, or cholesterol to a molecule called propionyl-CoA. Using biotin, propionyl-CoA carboxylase then converts propionyl-CoA to a molecule called methylmalonyl-CoA. Additional enzymes break down methylmalonyl-CoA into other molecules that are used for energy.
Related Information
More than 45 mutations in the PCCA gene have been identified in people with propionic acidemia. These mutations include changes in single DNA building blocks (nucleotides) and insertions or deletions of genetic material in the PCCA gene. PCCA mutations prevent the production of functional propionyl-CoA carboxylase or reduce the enzyme's activity. The altered or missing enzyme is unable to process certain parts of proteins and lipids properly. As a result, propionyl-CoA and other potentially harmful compounds can build up to toxic levels in the body. This buildup damages the brain and nervous system, causing the serious health problems associated with propionic acidemia.
Related Information
Cytogenetic Location: 13q32, which is the long (q) arm of chromosome 13 at position 32
Molecular Location: base pairs 100,089,015 to 100,530,437 on chromosome 13 (Homo sapiens Annotation Release 108, GRCh38.p7) (NCBI)
Related Information
- PCCA_HUMAN
- PCCase alpha subunit
- propionyl CoA carboxylase, alpha polypeptide
- propionyl-CoA:carbon dioxide ligase alpha subunit
- propionyl Coenzyme A carboxylase, alpha polypeptide
Related Information
- Clavero S, Martínez MA, Pérez B, Pérez-Cerdá C, Ugarte M, Desviat LR. Functional characterization of PCCA mutations causing propionic acidemia. Biochim Biophys Acta. 2002 Nov 20;1588(2):119-25.
- Desviat LR, Clavero S, Perez-Cerdá C, Navarrete R, Ugarte M, Perez B. New splicing mutations in propionic acidemia. J Hum Genet. 2006;51(11):992-7. Epub 2006 Oct 19.
- Desviat LR, Pérez B, Pérez-Cerdá C, Rodríguez-Pombo P, Clavero S, Ugarte M. Propionic acidemia: mutation update and functional and structural effects of the variant alleles. Mol Genet Metab. 2004 Sep-Oct;83(1-2):28-37. Review.
- Pérez B, Desviat LR, Rodríguez-Pombo P, Clavero S, Navarrete R, Perez-Cerdá C, Ugarte M. Propionic acidemia: identification of twenty-four novel mutations in Europe and North America. Mol Genet Metab. 2003 Jan;78(1):59-67.
