PCCA

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.

propionic acidemia - caused by mutations in the PCCA gene

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.