Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Propionyl-CoA carboxylase (PCC) catalyzes the biotin-dependent carboxylation of propionyl-CoA to d-methylmalonyl-CoA in the mitochondrial matrix. Human PCC is a dodecamer composed of pairs of nonidentical alpha and beta subunits encoded by PCCA and PCCB genes, respectively. Deficiency of PCC results in propionic acidemia (PA), a metabolic disorder characterized by severe metabolic ketoacidosis, vomiting, lethargy, and hypotonia. To date, almost 60 mutations have been reported in both genes. Exon 15 of the beta subunit is one of the two sites where a number of mutations have been identified in PA patients. In the primary betaPCC sequence, these mutations lead to three substitutions (R512C, L519P, and N536D), three truncations (R499X, R514X, and W531X), and one insertion (A51_R514insP). We expressed these mutant proteins in Escherichia coli in which the GroESL complex was overexpressed. The only mutation that does not impact the stability of mutant betaPCC in bacteria is W531X. The remaining mutations lead to either complete (L519P, N536D) or partial (R499X, R512C, A513_R514insP, and R514X) degradation of the mutant subunits. Size-exclusion chromatography revealed that R512C and W531X do not affect the assembly of alphaPCC and betaPCC to active oligomers. Specific activities for these mutant proteins, however, were only 3.9 and 10% of the wild type, respectively. Taken together, the carboxyl-terminal portion of 40 amino acid residues of the beta subunit affects the stability and the assembly of the alpha and beta subunits as well as the carboxylation of propionyl-CoA.
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PMID:Changes in the carboxyl terminus of the beta subunit of human propionyl-CoA carboxylase affect the oligomer assembly and catalysis: expression and characterization of seven patient-derived mutant forms of PCC in Escherichia coli. 1113 55

Propionic acidemia is a metabolic disorder (OMIM 606054) caused by deficiency of the propionyl-coenzyme A (CoA) carboxylase, which subsequently results in accumulation of propionic acid. Patients may initially present with poor feeding, vomiting, loss of appetite, hypotonia, and lethargy. Later, most children will show different degrees of motor, social and language delay even more serious medical problems, including heart abnormalities, seizures, coma, and possibly death. Two siblings affected with propionic acidemia were screened for putative mutations in PCCA and PCCB genes coding alpha and beta subunits of propionyl-coenzyme A (CoA) carboxylase, respectively. Both patients had a mild-severe form of propionic acidemia. The investigations using PCR, long-PCR, array comparative genomic hybridization (aCGH), and sequencing techniques showed a approximately 73kb deletion extending from intron 16 to intron 19 and an 18bp insertion at the distal end of the deletion in PCCA gene. The deletion so far is the largest gross change reported in the literature for the PCCA gene.
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PMID:Array comparative genomic hybridization (aCGH) reveals the largest novel deletion in PCCA found in a Saudi family with propionic acidemia. 1879 Jul 21

The autosomal recessive disease propionic acidemia (PA) is an inborn error of metabolism with highly variable clinical manifestations, caused by a deficiency of propionyl-CoA carboxylase (PCC) enzyme, due to mutations in either PCCA or PCCB genes, which encode the alpha and beta subunits of the PCC enzyme, respectively. The classical clinical presentation consists of poor feeding, vomiting, metabolic acidosis, hyperammonemia, lethargy, neurological problems, and developmental delay. PA seems to be a prevalent disease in the Arab World. Arab patients with PA seem to have the same classical clinical picture for PA with distinctive associated complications and other diseases. Most of the mutations found in Arab patients seem to be specific to the Arab population, and not observed in other ethnic groups. In this review, I will discuss in details the clinical and molecular profile of Arab patients with PA.
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PMID:Propionic acidemia in the Arab World. 2586 1

Propionyl-CoA carboxylase (PCC) is the enzyme which catalyzes the carboxylation of propionyl-CoA to methylmalonyl-CoA and is encoded by the genes PCCA and PCCB to form a hetero-dodecamer. Dysfunction of PCC leads to the inherited metabolic disorder propionic acidemia, which can result in an affected individual presenting with metabolic acidosis, hyperammonemia, lethargy, vomiting and sometimes coma and death if not treated. Individuals with propionic acidemia also have a number of long term complications resulting from the dysfunction of the PCC enzyme. Here we present an overview of the current knowledge about the structure and function of PCC. We review an updated list of human variants which are published and provide an overview of the disease.
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PMID:Propionyl-CoA carboxylase - A review. 2903 50