Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.1.1.41 (propionyl-CoA carboxylase)
 344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pseudomonas citronellolis was shown to contain four different acyl-coenzyme A carboxylases, including acetyl-, propionyl-, 3-methylcrotonyl-, and geranyl-CoA carboxylases, when grown on the appropriate carbon sources. Acetyl-CoA carboxylase activity in crude extracts was stimulated approximately 40-fold by inclusion of 0.4-0.5 M ammonium sulfate in the assay. Unexpectedly high levels of propionyl-CoA carboxylase activity, also stimulated by ammonium sulfate, were found in acetate-grown cells. That these acetyl- and propionyl-CoA carboxylase activities were due to different enzymes was shown by their resolution during purification by a procedure that stabilized acetyl-CoA carboxylase as a complex and separated propionyl-CoA carboxylase into two required protein fractions. Propionate- or valine-grown cells contained a propionyl-CoA carboxylase activity that was strongly inhibited by ammonium sulfate in the assay, and which may represent an inducible form of the enzyme. Geranyl- and 3-methylcrotonyl-CoA carboxylases that catalyze the carboxylation of the 3-methyl groups of homologous acyl-CoA acceptors, were induced by growth on the monoterpenes, citronellic or geranoic acid; only 3-methylcrotonyl-CoA carboxylase was induced by growth on leucine or isovaleric acid. Induction of either carboxylase was associated with the appearance of similar high-molecular-weight, biotin-containing proteins as measured by gel filtration. These two carboxylases are probably distinct enzymes since 3-methyl-crotonyl-CoA carboxylase from isovalerate-grown cells does not carboxylate geranyl-CoA, while geranyl-CoA carboxylase will carboxylate both acyl-CoA homologues. P. citronellolis appears to be a useful system for studying the structural aspects of pairs of homologous acyl-CoA carboxylases.
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PMID:Multiple acyl-coenzyme A carboxylases in Pseudomonas citronellolis. 0 91

Propionyl-CoA carboxylase and combined methylmalonyl-CoA (MMA-CoA) racemase and -mutase activities were studied in liver and fibroblasts of two patients with the acute neonatal form of nonketotic hyperglycemia. In all experiments, these enzyme activities studied in tissues of the patients were within the range of healthy control subjects, whereas no propionyl-CoA carboxylase activity was measurable in the fibroblasts of a patient with propionic acidemia. Subcellular fractionation of liver and fibroblasts indicated that the normal amounts of MMA-CoA found after incubation of whole tissue homogenate were formed by propionyl-CoA carboxylase, a mitochondrial enzyme, and not be acetyl-CoA carboxylase, which theoretically could also be involved in the carboxylation of propionyl-CoA. From the above data as well as from clinical and biochemical observations in three patients, it was concluded that there exists a true nonketotic hyperglycinemia which is not related etiologically to the different disorders of the ketotic hyperglycinemia syndrome. True nonketotic hyperglycinemia is not associated with ketoacidosis even after loading with propionate- and MMA precursors. It must be distinguished by exclusion from mild forms of the ketotic hyperglycinemia syndrome which may present clinically as hyperglycinemia without ketosis.
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PMID:Acute neonatal nonketotic hyperglycinemia: normal propionate and methylmalonate metabolism. 24 Jan 44

The effects of 18 normally occurring and 11 patalogical metabolites of the branched-chain amino acids on the glycine cleavage system were investigated on intact rat liver mitochondria. It was demonstrated, that 2-oxo-isovaleric acid, 2-methyl-butyric acid, and isobutyric acid significantly inhibited the glycine cleavage system in intact mitochondria. Further studies on the solubilized glycine cleavage system demonstrated that the inhibitory effect was due to 2-methyl-butyryl-CoA (linear noncompetitive inhibition, ki: 0.1--0.15 mM) and isobutyryl-CoA (S-hyperbolic, I-linear noncompetitive inhibition, ki: 0.2--0.3 mM). Both 2-methyl-butyric acid and isobutyric acid exhibited less inhibition (2-methyl-butyric acid: competitive inhibition, ki: 5.5 mM, isobutyric acid: competitive inhibition, ki: 16 mM), while 2-oxo-isovaleric acid was without inhibitory effect, and probably affects intact mitochondria through transformation to isobutyryl-CoA. It is suggested that the inhibitory action of 2-methyl-butyryl-CoA and isobutyryl-CoA may explain the hyperglycinemia seen in propionyl-CoA carboxylase deficiency, methyl-malonyl-CoA mutase deficiency and beta-ketothiolase deficiency.
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PMID:Inhibition of the glycine cleavage system by branched-chain amino acid metabolites. 48 63

A number of previously unrecognized abnormal metabolites have been identified and quantitated in the urine of a patient with an inherited deficiency of propionyl-CoA carboxylase. These included the isoleucine metabolites 2-methyl-3-hydroxybutyric acid and 2-methylacetoacetic acid. These isomers 3-hydroxyvaleric acid and 3-oxovaleric acid were found, which may be products of the condensation of propionyl-CoA with acetyl-CoA catalyzed by 3-oxoacyl-CoA thiolases. Following a load of isoleucine, 2-methylbutyrylglycine was identified. This metabolite has not previously been observed in man.
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PMID:Abnormal metabolites of isoleucine in a patient with propionyl-CoA carboxylase deficiency. 63 60

We measured propionyl coenzyme A carboxylase (PCC) activity in extracts of skin fibroblasts and peripheral blood leukocytes from controls and obligate heterozygotes for PCC deficiency. 6 heterozygotes were from the pcc A complementation group; 12 were from the other major complementation group, designated pcc C. Mean PCC activity in fibroblast extracts from pcc A heterozygotes was 52% of that in controls, whereas mean PCC activity in pcc C heterozygotes was indistinguishable from that of controls. Similar results were obtained with extracts of peripheral blood leukocytes. In none of eight families (three pcc A and five pcc C) in which PCC activity was studied in both parents of an affected child were significant intrafamilial differences observed. The activities of two other mitochondrial enzymes (beta-methyl-crotonyl CoA carboxylase and glutamate dehydrogenase) were comparable in controls and both groups of heterozygotes. Whereas the data from pcc A heterozygotes are consistent with expected gene dosage effects, those from pcc C heterozygotes are not. Inasmuch as mammalian PCC is a large molecular weight tetramer, each protomer of which is probably composed of two nonidentical subunits, the latter results are most consistent with unbalanced rates of synthesis and(or) degradation of the two subunits in normal cells with compensatory balancing in pcc C heterozygotes.
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PMID:Heterozygote expression in propionyl coenzyme A carboxylase deficiency. Differences between major complementation groups. 71 58

When beta-fluoropropionyl coenzyme A is used as substrate, propionyl-CoA carboxylase catalyzes the formation of ADP and the elimination of fluoride ion. No F- release occurs in the absence of ATP or in the presence of avidin. ADP formation occurs as rapidly as in the presence of propionyl-CoA, but the rate of F- release is 6 times that of ADP formation. The rate of F- release is indicative of the minimal rate of abstraction of the alpha proton, and the rate of ADP formation is equivalent to the rate of formation of biotin-CO2. The results, therefore, show that hydrogen abstraction can occur without concomitant CO2 transfer from biotin-CO2 to the substrate. Therefore, the concerted mechanism which has been proposed for this, and other biotin enzymes, is not applicable when propionyl-CoA carboxylase acts on beta-fluoropropionyl-CoA. We believe the concerted mechanism is also not involved in the carboxylation of the normal substrate, propionyl-CoA.
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PMID:Biotin carboxylations--concerted or not concerted? That is the question! 92 96

We report characterization of the component proteins and molecular cloning of the genes encoding the two subunits of the carboxyltransferase component of the Escherichia coli acetyl-CoA carboxylase. Peptide mapping of the purified enzyme component indicates that the carboxyltransferase component is a complex of two nonidentical subunits, a 35-kDa alpha subunit and a 33-kDa beta subunit. The alpha subunit gene encodes a protein of 319 residues and is located immediately downstream of the polC gene (min 4.3 of the E. coli genetic map). The deduced amino acid composition, molecular mass, and amino acid sequence match those determined for the purified alpha subunit. Six sequenced internal peptides also match the deduced sequence. The amino-terminal sequence of the beta subunit was found within a previously identified open reading frame of unknown function called dedB and usg (min 50 of the E. coli genetic map) which encodes a protein of 304 residues. Comparative peptide mapping also indicates that the dedB/usg gene encodes the beta subunit. Moreover, the deduced molecular mass and amino acid composition of the dedB/usg-encoded protein closely match those determined for the beta subunit. The deduced amino acid sequences of alpha and beta subunits show marked sequence similarities to the COOH-terminal half and the NH2-terminal halves, respectively, of the rat propionyl-CoA carboxylase, a biotin-dependent carboxylase that catalyzes a similar carboxyltransferase reaction reaction. Several conserved regions which may function as CoA-binding sites are noted.
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PMID:The genes encoding the two carboxyltransferase subunits of Escherichia coli acetyl-CoA carboxylase. 135 89

We developed a coupled NaH14CO3 fixation assay to detect 3-oxothiolase deficiency in extracts of cultured human fibroblasts. Cell extracts were incubated with tiglyl-CoA, NAD, CoASH, ATP and NaH14CO3. The enzymatic activities of tiglyl-CoA (enoyl-CoA) hydratase, 2-methyl-3-hydroxybutyryl-CoA dehydrogenase and 2-methylacetoacetyl-CoA thiolase (3-oxothiolase) were coupled to produce propionyl-CoA. Propionyl-CoA produced in the assay was estimated by fixation of NaH14CO3 into [14C]methylmalonyl-CoA employing endogenous propionyl-CoA carboxylase. The control activity was 32 +/- 23 pmol/min per mg protein (+/- 1 S.D., range 7-94; 28 cell lines). Five known cases of 3-oxothiolase deficiency had a mean activity of 2% of the control; a sixth case of 3-oxothiolase deficiency was significantly higher at 27% of the mean control value. Coupled assay activity was also low (3% of control) in the cells from a patient with propionyl-CoA carboxylase deficiency.
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PMID:A coupled assay detecting defects in fibroblast isoleucine degradation distal to enoyl-CoA hydratase: application to 3-oxothiolase deficiency. 135 1

The unresolved autotrophic CO2 fixation pathways in the sulfur-reducing Archaebacterium Thermoproteus neutrophilus and in the phototrophic Eubacterium Chloroflexus aurantiacus have been investigated. Autotrophically growing cultures were labelled with [1,4-13C1]succinate, and the 13C pattern in cell constituents was determined by 1H- and 13C-NMR spectroscopy of purified amino acids and other cell constituents. In both organisms succinate contributed to less than 10% of cell carbon, the major part of carbon originated from CO2. All cell constituents became 13C-labelled, but different patterns were observed in the two organisms. This proves that two different cyclic CO2 fixation pathways are operating in autotrophic carbon assimilation in both of which succinate is an intermediate. The 13C-labelling pattern in T. neutrophilus is consistent with the operation of a reductive citric acid cycle and rules out any other known autotrophic CO2 fixation pathway. Surprisingly, the proffered [1,4-13C1]succinate was partially converted to double-labelled [3,4-13C2]glutamate, but not to double-labelled aspartate. These findings suggest that the conversion of citrate to 2-oxoglutarate is readily reversible under the growth conditions used, and a reversible citrate cleavage reaction is proposed. The 13C-labelling pattern in C. aurantiacus disagrees with any of the established CO2 fixation pathways; it therefore demands a novel autotrophic CO2 fixation cycle in which 3-hydroxypropionate and succinate are likely intermediates. The bacterium excreted substantial amounts of 3-hydroxypropionate (5 mM) and succinate (0.5 mM) at the end of autotrophic growth. Autotrophically grown Chloroflexus cells contained acetyl-CoA carboxylase and propionyl-CoA carboxylase activity. These enzymes are proposed to be the main CO2-fixing enzymes resulting in malonyl-CoA and methylmalonyl-CoA formation; from these carboxylation products 3-hydroxypropionate and succinate, respectively, can be formed.
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PMID:13C-NMR study of autotrophic CO2 fixation pathways in the sulfur-reducing Archaebacterium Thermoproteus neutrophilus and in the phototrophic Eubacterium Chloroflexus aurantiacus. 157 76

Veillonella parvula cannot grow with succinate as sole energy source. However, succinate decarboxylation simultaneous with malate or lactate fermentation increased growth yields by 2.4-3.5 g (mol succinate)-1. Malate was fermented stoichiometrically to acetate and propionate whereas lactate fermentation produced more acetate and considerable amounts of H2. Aspartate was utilized only in the presence of succinate as co-substrate. Methylmalonyl-CoA decarboxylase and ATP-dependent pyruvate carboxylase, but not methylmalonyl-CoA:pyruvate transcarboxylase, were detected in cell-free extracts of malate- or lactate-grown cells. The energetic aspects of these fermentation patterns are discussed.
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PMID:Energy conservation by succinate decarboxylation in Veillonella parvula. 164 32


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