Propionicacidemia is an autosomal recessive
metabolic disease resulting from a deficiency of
propionyl-CoA carboxylase (PCC) activity. The
enzyme has the structure alpha 4 beta 4, with the alpha chain containing a covalently bound
biotin prosthetic group. Patients have been placed into two major complementation groups,
pccA and pccBC, that may correspond to the genes encoding the alpha and beta chains of PCC. The pccBC group is further divided into two subgroups, pccB and pccC, apparently owing to intragenic complementation. We previously reported combined alpha- and beta-chain deficiency in
pccA mutants and absence of beta chain in pccC and pccBC mutants after
isotope-tracer labeling and immunoprecipitation of cultured-fibroblast extracts. Using
cDNA clones coding for the alpha and beta chains as probes, we found absence of alpha
mRNA in four of six
pccA strains and presence of beta
mRNA in all
pccA mutants studied. We also found presence of both alpha and beta mRNAs in three pccBC, two pccB, and three pccC mutants. From these data, we confirm the gene assignments of the complementation groups (
PCCA gene =
pccA complementation group; PCCB gene = pccBC and subgroups) and support the view that
pccA patients synthesize a normal beta chain that is rapidly degraded in the absence of complexing with alpha chains.