Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:6.4.1.1 (pyruvate carboxylase)
1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biotin-protein populations in several bacterial strains were analyzed by solubilization of [3H]biotin-labeled cells with sodium dodecylsulfate followed by electrophoresis on polyacrylamide gels containing the detergent. A variety of patterns of biotin-labeled polypeptide chains was seen, ranging from a single biotin-protein in Escherichia coli, corresponding to the biotin carboxyl carrier protein component of acetyl-CoA carboxylase, to multiple species in Enterobacter aerogenes, Pseudomonas citronellolis, Bacillus cereus, Propionibacterium shermanii, Lactobacillus plantarum, and Mycobacterium phlei, which probably represent subunits of multiple biotin-dependent enzymes present in these organisms. In the case of Pseudomonas citronellolis two major biotin-containing polypeptides with approximate molecular weights of 65 000 and 25 000 were shown to correspond to the biotin carboxyl carrier components of pyruvate carboxylase and acetyl-CoA carboxylase, respectively. Thus in the case of Pseudomonas citronellolis two different biotin-dependent enzymes in the same cell do not share common biotin carboxyl carrier subunits.
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PMID:Analysis of bacterial biotin-proteins. 23 15

1. Birds affected by fatty liver and kidney syndrome (FLKS) had elevated concentrations of serum Na+, K+, lactate, pyruvate and uric acid and reduced concentrations of serum HCO-3 and glucose. 2. Short-term treatment with biotin or animal tallow reduced the mortality from FLKS and prevented the clinical signs. 3. Lactic acidosis may be a major factor contributing to the mortality and physical symptoms observed in birds affected by FLKS. The lactic acidosis and the hypoglycaemia observed in FLKS are due primarily to an accumulation of pyruvate as a result of an insufficiency of biotin for normal pyruvate carboxylase activity.
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PMID:Clinical signs of fatty liver and kidney syndrome in broilers and their alleviation by the short-term use of biotin or animal tallow. 59 40

Using perfused livers of rats fasted for 48 hours, glucose production and incoroporation of 2-14C pyruvate (trace dose) into perfusate glucose were studied. Both were found to be inhibited by PGE1 (infuced at a concentration of 0.5 mu/min) by about 60%. The incorporation of 1-14C glycerol into perfusate glucose and into glycerol-glyceride part of the liver glycerides were also studied, using the same test conditions. The former incorporation was significantly inhibited (56%) and the latter strongly stimulated (360 %) by PGE1. PGE1 had no effect on glucose production in a perfusate overloaded with sodium pyruvate, nor on pyruvate carboxylase and phospho-enolpyruvate carboxykinase activity. this was in contrast with the results obtained in perfusions with a trace dose of 2-14C pyruvate. The results showed that PGE1, at the physiological concentration used, stimulated the incorporation of 1-14C glycerol into glycerol-glyceride part of liver glycerides and, when there was no overload of pyruvate present in the perfusion medium, inhibited gluconeogensis at some point, possibly, but perhaps not exclusively, between the glycerol and glucose steps.
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PMID:Effect of PGE1 on gluconeogenesis and glycerol esterification in perfused liver of fasted rats. 116 94

The 2' , 3'-dialdehyde derivative of ATP (oATP) was prepared by periodate oxidation and on the following criteria was considered to be an effective affinity label. The magnesium complex of this derivative (Mg-oATP2) was shown to ba linear competitive inhibitor with respect to MgATP2-in both the acetyl-CoA-dependent and -independent activities of the enzyme but was a non-competitive inhibitor with respect to bicarbonate, and an uncompetitive inhibitor with respect to pyruvate. Mg-oATP was covalently bound to pyruvate carboxylase by reduction using sodium borohydride with concurrent irreversible inactivation of the enzyme...
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PMID:Pyruvate carboxylase: affinity labelling of the magnesium adenosine triphosphate binding site. 124 74

Biotin-dependent enzymes are involved in carboxylation, decarboxylation and transcarboxylation reactions. Here, we have used sodium dodecyl sulfate polyacrylamide gel electrophoresis and electroblotting followed by probing with avidin to identify biotin-containing polypeptides in Dictyostelium discoideum. Twenty biotinyl polypeptides were visualized, with a 23 kDa protein appearing transiently. Based upon the molecular mobility of the biotinyl polypeptides, D. discoideum may contain the biotin-dependent enzymes acetyl CoA carboxylase, proprionyl CoA carboxylase, pyruvate carboxylase, and 3-methylcrotonyl CoA carboxylase.
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PMID:Endogenous biotinylated proteins in Dictyostelium discoideum. 167 51

Synthesis of glucose from lactate and generation of urea from ammonia were inhibited when sodium benzoate was added to suspensions of rat hepatocytes. Assays with isolated mitochondria suggested pyruvate carboxylase and the N-acetyl-L-glutamate (NAG)-dependent carbamoylphosphate synthetase (CPS-I) as potential sites of inhibition for both pathways, owing to a shared dependency on aspartate efflux from the mitochondria and its subsequent conversion to oxaloacetate in the cytosol. Assays with isolated hepatocytes indicated inhibition to be initiated by accumulation of benzoyl CoA with a resultant depletion of free CoA and acetyl CoA. Measurements of adenine nucleotides showed that benzoate metabolism did not sufficiently alter energy status to account for the observed inhibition. Consistent with these interpretations, acceleration of the conversion of benzoyl CoA to hippurate by the addition of glycine restored the levels of free CoA and acetyl CoA and the rates of gluconeogenesis and ureagenesis. Reduction of the levels of aspartate and glutamate, presumably by interference with the anapleurotic function of pyruvate carboxylase, most likely accounted for inhibition of gluconeogenesis by benzoate. Whether reduced flux through the urea cycle also contributed to inhibition of gluconeogenesis (by diminishing cytosolic conversion of aspartate to oxaloacetate) requires further study. Depression of glutamate and acetyl CoA to levels at or below the Km for NAG synthetase probably accounted for the observed inhibition of ureagenesis. Rates of urea production were observed to vary with changes in the levels of NAG, suggesting NAG-dependent CPS-I to be the primary site of inhibition of ureagenesis by benzoate.
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PMID:On the mechanism of inhibition of gluconeogenesis and ureagenesis by sodium benzoate. 167 73

Pyruvate-dependent CO2 fixation by isolated mitochondria was strongly inhibited by sodium benzoate. Pyruvate carboxylase was identified as a site of inhibition by limiting flux measurements to assays of pyruvate carboxylase coupled with malate dehydrogenase. Benzoate reduced pyruvate-dependent incorporation of [14C]KHCO3 into malate and pyruvate-dependent malate accumulation by 74 and 72%, respectively. Aspartate-dependent malate accumulation was insensitive to benzoate, ruling out malate dehydrogenase as a site of action. Inhibition by benzoate was antagonized by glycine, which sharply accelerated conversion of benzoate to hippurate. Assays of coenzyme A and its acyl derivatives revealed inhibition to correlate with depletion of acetyl CoA and accumulation of benzoyl CoA. Depletion of acetyl CoA was sufficient to account for greater than 50% reduction in pyruvate carboxylase activity. Competition between acetyl CoA and benzoyl CoA for the activator site on pyruvate carboxylase was insignificant. Results support the interpretation that the observed inhibition of pyruvate carboxylase occurred primarily by depletion of the activator, acetyl CoA, through sequestration of coenzyme A during benzoate metabolism.
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PMID:Inhibition of pyruvate carboxylase by sequestration of coenzyme A with sodium benzoate. 249 93

Peroxidase-conjugated avidin was used to detect biotin-containing carboxylases in rat liver. By a transblot method, avidin-peroxidase interacted with liver proteins with estimated molecular masses of 120 and 74 kDa. The proteins were identified as pyruvate carboxylase (120 kDa, 6.4 pI) and methylcrotonyl-CoA carboxylase (74 kDa, 7.2 pI) by two-dimensional gel electrophoresis and transblot method. An additional band with estimated molecular mass of 220 kDa was detected in the cytosol fraction of rat liver, compatible with acetyl-CoA carboxylase. Rat liver proteins were prepared and treated with avidin and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and transblot with avidin-peroxidase. A 190-kDa band was found with a parallel decrease in the 120-kDa band determined by Coomassie blue staining; however, these proteins did not stain by the transblot avidin-peroxidase method. When the transblot of parallel proteins was incubated with biotin and subsequently with avidin-peroxidase, two additional bands, namely 190 and 145 kDa, were detected while the 74-kDa band disappeared correlated with decreased staining of the 120-kDa band. The present procedure is a simple, rapid, and inexpensive method for detecting biotin-containing proteins in various tissues and organs and in determining the occurrence of nonspecific staining with the avidin-biotin complex method of immunoblot.
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PMID:Transblot identification of biotin-containing proteins in rat liver. 274 54

Incubation of cultured cells with [3H]biotin leads to the labelling of acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase and methylcrotonyl-CoA carboxylase. The biotin-containing subunits of the last two enzymes from rat cell lines are not separated by sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, but adequate separation is achieved with the enzymes from human cells. Since incorporated biotin is only released upon complete protein breakdown, the loss of radioactivity from gel slices coinciding with fluorograph bands was used to quantify degradation rates for each protein. In HE(39)L diploid human fibroblasts, the degradation rate constants are 0.55, 0.40, 0.31 and 0.19 day-1 for acetyl-CoA carboxylase, pyruvate carboxylase, methylcrotonyl-CoA carboxylase and propionyl-CoA carboxylase respectively. A similar series of rate constants is found for AG2804 transformed fibroblasts. The degradation rate constants are decreased by 31-67% in the presence of 50 micrograms of leupeptin/ml plus 5 mM-NH4Cl. Although the largest percentage effect was noted with the most stable enzyme, propionyl-CoA carboxylase, the absolute change in rate constant produced by the lysosomotropic inhibitors was similar for the three mitochondrial carboxylases, but greater for the cytosolic enzyme acetyl-CoA carboxylase. The heterogeneity in degradation rate constants for the mitochondrial carboxylases indicates that only part of their catabolism can occur via the autophagy-mediated unit destruction of mitochondria. Calculations showed that the autophagy-linked process had degradation rate constants of 0.084 and 0.102 day-1 respectively in HE(39)L and AG2804 cells. It accounted for two-thirds of the catabolic rate of propionyl-CoA carboxylase and a lesser proportion for the other enzymes.
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PMID:Distribution and degradation of biotin-containing carboxylases in human cell lines. 286 10

Cultured skin fibroblasts from 16 patients with either French or American pyruvate carboxylase (PC) deficiency were examined for their ability to incorporate 3H-biotin into proteins. Cell extracts were also examined for the presence of biotin-containing proteins with 35S-streptavidin, immunoreactive protein with anti-PC antibody, and PC mRNA by Northern blotting with a PC cDNA probe. All the North American presentation patients showed a 3H-biotin protein, a streptavidin protein, and an anti-PC precipitable protein at 125 kilodaltons on sodium dodecyl sulfate-polyacrylamide gel electrophoresis of cellular proteins. They also showed a detectable mRNA species for PC on Northern blotting. Of the French presentation patients, five showed very low or absent 3H-biotin protein, streptavidin protein, and anti-PC precipitable protein at 125 kilodaltons. Three French presentation patients showed PC protein to be present on the basis of these techniques. Similarly, five showed either very low or absent mRNA for PC on Northern blotting whereas three gave evidence of the presence of PC-specific mRNA. Thus, whereas the North American presentation of PC deficiency is associated with the presence of a mature biotin containing protein of the correct molecular weight, the French presentation may, in some (but not in all) cases, have both absent PC protein and absent PC mRNA.
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PMID:The French and North American phenotypes of pyruvate carboxylase deficiency, correlation with biotin containing protein by 3H-biotin incorporation, 35S-streptavidin labeling, and Northern blotting with a cloned cDNA probe. 310 94


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