Disease relevance of Propionyl coenzyme A

• We have determined the 2.9-Angstroms crystal structure of AccD5, whose sequence, structure, and active site are highly conserved with respect to the carboxyltransferase domain of the Streptomyces coelicolor propionyl-CoA carboxylase [1].
• On the basis of sequence homology with the Propionibacterium shermanii transcarboxylase 12S subunit, we suggest that the pccC domain, defined by Ile408 and Arg410, may involve the propionyl-CoA binding site [2].
• Chaperonin-mediated assembly of wild-type and mutant subunits of human propionyl-CoA carboxylase expressed in Escherichia coli [3].
• Propionyl-CoA carboxylase (EC 6.4.1.3) has been purified from Mycobacterium smegmatis [4].
• Erythromycin production in Saccharopolyspora erythraea does not require a functional propionyl-CoA carboxylase [5].

High impact information on Propionyl coenzyme A

• The diagnosis was confirmed by demonstration of deficient activity of propionyl-CoA carboxylase in cells cultured from the amniotic fluid and in fetal tissues [6].
• We further hypothesized that replacing dietary medium-even-chain fatty acids (precursors of acetyl-CoA) by medium-odd-chain fatty acids (precursors of acetyl-CoA and anaplerotic propionyl-CoA) would restore energy production and improve cardiac and skeletal muscle function [7].
• Here, we report the obligatory participation of HCS in the biotin-dependent stimulation of the level of HCS mRNA and those of acetyl-CoA carboxylase and the alpha subunit of propionyl-CoA carboxylase in human cells [8].
• Expression of the cDNA clones promoted biotinylation of the bacterial biotinyl carboxyl carrier protein as well as a carboxyl-terminal fragment of the alpha subunit of human propionyl-CoA carboxylase expressed from a plasmid [9].
• Isolation of cDNA clones coding for the alpha and beta chains of human propionyl-CoA carboxylase: chromosomal assignments and DNA polymorphisms associated with PCCA and PCCB genes [10].

Chemical compound and disease context of Propionyl coenzyme A

• Since propionate absorbed from the intestine can be converted to propionyl-CoA in the liver, inhibition of propionyl-CoA synthesis from propionate and CoA may provide a strategy for decreasing toxicity from plasma propionate [11].
• The genetic operon for propionic acid degradation in Salmonella enterica serovar Typhimurium contains an open reading frame designated prpE which encodes a propionyl coenzyme A (propionyl-CoA) synthetase (A. R. Horswill and J. C. Escalante-Semerena, Microbiology 145:1381-1388, 1999) [12].
• The deduced amino acid sequences of the product of these two genes showed high similarity to BcpA2 of Saccharopolyspora erythraea and other biotin-containing proteins from different organisms assumed to be the alpha subunit of a propionyl-CoA carboxylase [13].
• Methylmalonyl-CoA decarboxylase catalyses the only energy-conserving step during succinate fermentation by Propionigenium modestum: the decarboxylation of (S)-methylmalonyl-CoA to propionyl-CoA is coupled to the vectorial transport of Na+ across the cytoplasmic membrane, thereby creating a sodium ion motive force that is used for ATP synthesis [14].
• There is no relationship to the trans-2-enoyl-CoA reductases from various organisms or the recently described acryloyl-CoA reductase activity of propionyl-CoA synthase from Chloroflexus aurantiacus [15].

Biological context of Propionyl coenzyme A

• An open reading frame of 1623 nucleotides, flanked by stop codons, encodes a polypeptide of 541 amino acids; the predicted amino acid sequence was confirmed as that of the beta subunit of propionyl-CoA carboxylase by matching it to the amino acid sequences of five peptides derived from pure mature rat enzyme [16].
• At substrate concentrations of 0.5 mM, the relative rate of hydrolysis of CoA esters was as follows: D-methylmalonyl-CoA (100%), malonyl-CoA (16%), propionyl-CoA (3%), acetyl-CoA (1%), succinyl-CoA (less than 1%), and palmitoyl-CoA (less than 1%) [17].
• Fatal propionic acidemia in mice lacking propionyl-CoA carboxylase and its rescue by postnatal, liver-specific supplementation via a transgene [18].
• High levels of propionyl-CoA greatly reduced acetylation by acetyl-CoA and nearly prevented activation of kinase activity by acetyl-CoA.(ABSTRACT TRUNCATED AT 400 WORDS)[19]
• Sequence analysis, biogenesis, and mitochondrial import of the alpha-subunit of rat liver propionyl-CoA carboxylase [20].

Anatomical context of Propionyl coenzyme A

• Mutant fibroblasts with a deficiency of propionyl-CoA carboxylase activity (EC 6.4.1.3) that had been mapped to complementation groups pcc and bio were used to evaluate the microtechnique [21].
• 3-Methylcrotonyl-CoA carboxylase (MCase; EC 6.4.1.4) and propionyl-CoA carboxylase (PCase; EC 6.4.1.3) have been obtained in highly purified form from bovine kidney mitochondria [22].
• An incidental discovery of this study was the identification of a high level of propionyl-CoA carboxylase activity and a lesser amount of methylcrotonyl-CoA carboxylase activity in pancreatic islets [23].
• A novel glucokinase regulator in pancreatic beta cells: precursor of propionyl-CoA carboxylase beta subunit interacts with glucokinase and augments its activity [24].
• Lymphocyte propionyl-CoA carboxylase and its activation by biotin are sensitive indicators of marginal biotin deficiency in humans [25].

Associations of Propionyl coenzyme A with other chemical compounds

• Two peaks of activity were clearly visible in mitochondria, one with an optimum at propionyl-CoA ("short-chain hydrolase") and one with an optimum at nonanoyl-CoA ("medium-chain hydrolase"); there was only low activity toward palmitoyl-CoA and longer-chain acyl-CoAs [26].
• We detected a cDNA encoding the precursor of propionyl-CoA carboxylase beta subunit (pbetaPCCase), and glutathione S-transferase pull-down assay illustrated that pbetaPCCase interacted with recombinant rat islet glucokinase and with glucokinase in rat liver and islet extracts [24].
• It was concluded that pent-4-enoate can be effectively metabolized in the myocardium and that its metabolism probably proceeds via propionyl-CoA, since pent-4-enoate reproduces many of the metabolic characteristics of propionate in the cardiac muscle [27].
• The consequences of this metabolic defect in vivo and in vitro are those predicted on the basis of propionyl-CoA and methylmalonyl-CoA accumulation [28].
• Acetyl-CoA synthase (EC 6.2.1.1), Propionyl-CoA synthase (EC 6.2.1.-) and butyryl-CoA synthase (EC 6.2.1.2) were measured in subcellular fractions prepared by primary and density-gradient fractionation from adult rat brain by a method resulting in recoveries close to 100% [29].

Gene context of Propionyl coenzyme A

• Mutations in the PCCA or PCCB genes, encoding both subunits of propionyl-CoA carboxylase, result in propionic acidemia, a life-threatening inborn error of metabolism with autosomal recessive inheritance [30].
• The PPARalpha targeted genes CPT-II and HMG-CoA synthase are potential regulators of mitochondrial fatty acid oxidation and ketogenesis in hTNFalpha transgenic mice, and the increased propionyl-CoA level found is a possible inhibitor of these processes [31].
• The sbm and ygfG genes encode a novel (2R)-methylmalonyl-CoA mutase and a (2R)-methylmalonyl-CoA decarboxylase, respectively, which convert succinyl-CoA, derived from the tricarboxylic acid cycle, to propionyl-CoA, an essential precursor of 3-hydroxyvalerate (HV) [32].
• We have determined the partial nucleotide sequence of cDNA clones for human propionyl-CoA carboxylase and pyruvate carboxylase [33].
• Heterologous expression of accA1, accA2 and pccB in Escherichia col and in vitro reconstitution of enzyme activity confirmed that PccB is the beta subunit of a propionyl-CoA carboxylase and that either AccA1 or AccA2 could act as the alpha component of this enzyme complex [13].

Analytical, diagnostic and therapeutic context of Propionyl coenzyme A

• An incidental finding of the current study was the discovery of beta-methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase in the islet [34].
• SDS-PAGE revealed that the subunits of propionyl-CoA synthase had been cleaved once and the N-terminal amino acid sequences of the two trypsin digestion products were determined [35].
• In this study, we have expressed carboxyl-terminal fragments of the alpha subunit of human propionyl-CoA carboxylase (PCC-alpha) in Escherichia coli and used site-directed mutagenesis to determine the sequence requirements for biotinylation by the bacterial holoenzyme synthetase [36].
• Correction of the metabolic defect in propionic acidemia fibroblasts by microinjection of a full-length cDNA or RNA transcript encoding the propionyl-CoA carboxylase beta subunit [37].
• In maternal and fetal liver, acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and beta-methylcrotonyl-CoA carboxylase abundances were determined by Western blotting; the content of mRNAs for most of these enzymes and holocarboxylase synthetase was determined by real-time RT-PCR [38].

References