Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:6.4.1.1 (pyruvate carboxylase)
 1,516 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An investigation was made of the interaction of pyruvate carboxylase with its allosteric effector, acetyl-CoA, and the velocity profile of the deacylation of acetyl-CoA as a function of acetyl-CoA concentration indicated that this ligand does not bind to this enzyme in a positive homotropic co-operative manner. An examination was therefore made of the factors that contribute to the sigmoidicity of the rate curves obtained for pyruvate carboxylation with various concentrations of acetyl-CoA. Hill coefficients for acetyl-CoA obtained with both sheep and chicken liver pyruvate carboxylases were found to be dependent on the fixed pyruvate concentration used in the assay solution. Thus, by varying the acetyl-CoA concentration, the degree of saturation of the enzyme by pyruvate was also changed. A further consequence of non-saturating concentrations of pyruvate was that the non-productive hydrolysis of the enzyme- carboxybiotin complex increased, resulting in an under-estimate of the reaction velocity measured by oxaloacetate formation. Another factor contributing to the sigmoidicity is that, at non-saturating concentrations of acetyl-CoA, the enzyme undergoes inactivation upon dilution to low protein concentrations, again resulting in an under-estimate of the reaction velocity. Under conditions where none of the above factors was operating and the only effect of varying acetyl-CoA concentrations was to alter the proportion of the enzyme catalysing the carboxylation reaction at acetyl-CoA-dependent and -independent rates, the sigmoidicity of the acetyl-CoA velocity profile was completely eliminated.
 ...
PMID:The atypical velocity response by pyruvate carboxylase to increasing concentrations of acetyl-coenzyme A. 47 64

Analysis of the native enzyme and of the subunits produced upon its denaturation shows that pyruvate carboxylase from a thermophilic Bacillus is a tetramer with a molecular weight (mean value) of 558,000 and that the four polypeptide subunits are probably identical. The three functions (carboxyl carrier, carboxylation, and carboxyl transfer) in the pyruvate carboxylation reaction must therefore reside in this quarter-molecular polypeptide. The enzyme molecule contains four atoms of zinc and four molecules of D-biotin, and in the electron microscope the disposition of its four subunits presents a rhombic appearance. Reaction of the denatured enzyme with 5,5'-dithiobis (2-nitrobenzoic acid) (DTNB) reveals 10 sulfhydryl groups/subunit. In the native enzyme less than one of these groups reacts with DTNB. By contrast, all of these groups (11/subunit) of the native chicken liver pyruvate carboxylase are accessible to DTNB. The thermophile enzyme is also more resistant to other sulfhydryl reagents and to denaturation under certain conditions than the avian enzyme.
 ...
PMID:Pyruvate carboxylase from a thermophilic Bacillus: some molecular characteristics. 47 75

Physical-chemical studies of pyruvate carboxylase from Pseudomonas citronellolis demonstrate that the enzyme has an alpha 4 beta 4 structure. The individual polypeptides, alpha (Mr = 65,000) and beta (Mr = 54,000), were separated and isolated by preparative gel electrophoresis. Analysis of the relationship between Coomassie blue staining and protein quantity for each polypeptide indicated that the alpha and beta subunits are present in a 1:1 stoichiometry in the native enzyme. Determinations of the molecular weight of the protein by sedimentation equilibrium (Mr = 454,000), gel filtration analysis (Mr = 510,000), disc gel electrophoresis (Mr = 530,000), and mass measurement from the Scanning Transmission Electron Microscope (Mr = 530,000) are consistent with the proposed alpha 4 beta 4 structure. Disc gel electrophoresis studies revealed that under certain circumstances the enzyme may dissociate to a smaller molecular weight species (Mr = 228,000). This dissociation phenomenon could explain the earlier reported observation of Taylor et al. ((1972) J. Biol. Chem 22, 7388-8390) that the enzyme had a molecular weight of 265,000. Evidence from electron microscopic studies shows that the three-dimensional structure of this enzyme is quite distinct from other species of pyruvate carboxylase. The enzyme does not show the typical rhombic appearance which has been noted for chicken liver, sheep liver, and yeast pyruvate carboxylase.
 ...
PMID:Quaternary structure of pyruvate carboxylase from Pseudomonas citronellolis. 47 94

From a strain of Bacillus stearothermophilus, devoid of active pyruvate carboxylase, a mutant (NG-15) was selected that grew on acetate in the presence of glucose. This mutant differed from its parent organism in possessing high activities of isocitrate lyase when grown on all carbon sources tested except nutrient broth, in possessing unusually low activities of NADP+-dependent isocitrate dehydrogenase and in containing increased amounts of isocitrate. Revertants of mutant NG-15 which regained the ability to synthesize active pyruvate carboxylase also synthesized isocitrate lyase and isocitrate dehydrogenase to the same extent as the wild-type strain. These results suggest that the regulatory mechanism for the synthesis of isocitrate lyase in the thermophile may be different from that in mesophilic bacilli.
 ...
PMID:The control of the synthesis of isocitrate lyase in a thermophilic bacillus. 47 37

Immunochemical techniques have been utilized to study the effect of thyroid status on the content and rates of synthesis and degradation of pyruvate carboxylase and pyruvate dehydrogenase in rat liver. Liver from hyperthyroid rats had twice the pyruvate carboxylase activity of normal rats while thyroidectomized rats had about two-thirds of normal activity. Pyruvate dehydrogenase complex activity was unchanged in the hyperthyroid state but was significantly reduced (by a third) in hypothyroid rats. Changes in catalytic activity during altered thyroid status were by immunochemical means to be closely related to the amount of the hepatic enzymes present. Isotopic studies showed that the changes in the content of pyruvate carboxylase and pyruvate dehydrogenase reflected alterations in the rate of the synthesis of the enzymes with the degradation rates little affected by thyroid status. The half-life for pyruvate carboxylase was 4.6 days, and that for pyruvate dehydrogenase, 8.1 days. In both cases, the turnover time was slower than that of the average mitochondrial protein (t1/2 = 3.8 days) for the control animals.
 ...
PMID:Effect of thyroid hormone on the turnover of rat liver pyruvate carboxylase and pyruvate dehydrogenase. 48 48

The influence of androgens on the male accessory glands of the rat was assessed in terms of changes in weight and of the specific activity of the mitochondrial enzymes, succinate dehydrogenase, glycerolphosphate dehydrogenase and pyruvate carboxylase, in the epididymis. In some instances, the activity of the cytoplasmic enzymes, hexokinase and phosphofructokinase, was also measured and the influence of androgens on these enzymes was found to be similar to that on the mitochondrial enzymes. After the administration of androgen to castrated rats the specific activity of enzymes reached a new steady state sooner than did epididymal weight. The time taken for the specific activity of the enzymes to reach a new steady state after the removal of androgen was variable, depending on the enzyme and the region of the epididymis. This time was generally longer, however, than the time taken for induction, and in the case of glycerolphosphate dehydrogenase, the decline of activity was slower in the cauda than in the caput. In castrated animals, about 100 times as much androgen was required to attain maximum tissue weight as was required to attain maximum enzyme activity. The epididymis, prostate and seminal vesicles responded similarly to androgen in terms of the dose-response pattern and the time taken for tissue weight to attain a new steady-state value, although the gain in weight of the epididymis relative to its weight in unstimulated control animals was less than the relative gain of the other accessory glands. Enzymes in the cauda epididymidis required lower amounts of androgen to elicit maximum activity than were required by those in the caput. The rate of change in the accessory glands in attaining new steady-state levels of tissue weight and enzyme activity was independent of the dose of androgen except during the first few days of hormone administration. Androgens were the most effective steroids in stimulating an increase of tissue weight and enzyme activity, although some changes were induced by oestradiol-3-benzoate and progesterone.
 ...
PMID:Influence of androgens on the weights of the male accessory reproductive organs and on the activities of mitochondrial enzymes in the epididymis of the rat. 49 85

Metabolic interactions between fatty acid oxidation and gluconeogenesis were investigated in vivo in 16h-old newborn rats under various nutritional states. As the newborn rat has no white adipose tissue, starvation from birth induces a low rate of hepatic fatty acid oxidation. Hepatic gluconeogenesis in inhibited in the starved newborn rat when compared with the suckling rat, which receives fatty acids through the milk, at the steps catalysed by pyruvate carboxylase and glyceraldehyde 3-phosphate dehydrogenase. These inhibitions are rapidly reversed by triacylglycerol feeding. Inhibition of fatty acid oxidation by pent-4-enoate in the suckling animal mimics the effect of starvation on the pattern of hepatic gluconeogenic metabolites. It is concluded that, in the newborn rat in vivo, hepatic fatty acids oxidation can increase the gluconeogenic flux by providing the acetyl-CoA necessary for the reaction catalysed by pyruvate carboxylase and the reducing equivalents (NADH) to displace the reversible reaction catalysed by glyceraldehyde 3-phosphate dehydrogenase in the direction of gluconeogenesis.
 ...
PMID:Interactions in vivo between oxidation of non-esterified fatty acids and gluconeogenesis in the newborn rat. 50

Pyruvate carboxylase activities of erythrocytes and liver preparations and their in vitro stimulation by biotin were used for the determination of the biotin status of chicks. Reasonable stability of the enzyme in erythrocytes was achieved when storing the erythrocytes deep-frozen in a glycerol-containing medium. Results of the activation assays in erythrocytes and liver are compared with biotin levels in feed, plasma and liver. The pyruvate carboxylase activation assay appears to be a useful tool for assessing the biotin status of chicks.
 ...
PMID:Pyruvate carboxylase activities in red blood cells and liver of chicks and their dependency on biotin status. First results with activation assays.. 55 86

A 3 X 2 factorial feeding study was conducted with channel catfish (Ictalurus punctatus) to evaluate effects of biotin, no biotin, or a biotin antagonist (avidin) in lipid and lipid-free diets. At 10 weeks, fish fed diets containing lipid were significantly larger than fish fed lipid-free diets. At 20 weeks, fish fed diets containing avidin had grown significantly less than those fed the other diets. At 22 weeks, fish fed the lipid diet supplemented with biotin had grown significantly more than those fed the lipid diet without biotin. Fish fed the lipid diet with avidin were found to be anemic and exhibited a marked depigmentation of the skin. Fish fed biotin in lipid and lipid-free diets had higher liver pyruvate carboxylase activity than fish fed diets without supplemental biotin. These results indicate that channel catfish require an exogenous source of biotin for maximum rates of growth and lipid utilization.
 ...
PMID:Essentiality of biotin for channel catfish (Ictalurus punctatus) fed lipid and lipid-free diets. 56 69

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.
 ...
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


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>