title: Assignment of the alpha and beta chains of human propionyl-CoA carboxylase to genetic complementation groups.
abstract: Propionicacidemia is a metabolic disorder resulting from a deficiency of propionyl-CoA carboxylase activity. The enzyme is composed of two polypeptides: a 72,000-dalton alpha chain which contains the biotin ligand and a 56,000-dalton beta chain. It has been suggested that the two major complementation groups in this disorder, pccA and pccBC (with subgroups pccB and pccC), correspond to the genes encoding these two chains. To correlate gene product with complementation groups, 15 mutant and four normal human fibroblast strains were analyzed by [35S]methionine and [3H]biotin labeling. Immunoprecipitation and gel electrophoresis of the polypeptides revealed that alpha chains are synthesized by mutants of pccBC and both subgroups but not in four out of five pccA mutants. On the other hand, beta chains were detected only in pccB mutants. We suggest that pccA encodes the alpha chain of PCC while pccBC encodes the beta chain, and furthermore predict that the beta chain is unstable in the absence of the alpha chain.
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology; D002262:Carboxy-Lyases / Q000172:deficiency / Q000235:genetics*; D002478:Cells, Cultured; D004591:Electrophoresis, Polyacrylamide Gel; D005347:Fibroblasts / Q000201:enzymology; D005796:Genes; D005816:Genetic Complementation Test; D006801:Humans; D007122:Immunoelectrophoresis; D043586:Methylmalonyl-CoA Decarboxylase; D009154:Mutation; D010455:Peptides / Q000032:analysis; D011422:Propionates / Q000097:blood; D014176:Protein Biosynthesis
chemical_list: D010455:Peptides; D011422:Propionates; D002262:Carboxy-Lyases; D043586:Methylmalonyl-CoA Decarboxylase