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:4.1.1.32 (phosphoenolpyruvate carboxykinase)
4,204 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of N6,O2'-dibutyryl cyclic adenosine monophosphate (Bt2cAMP) on the induction of the mRNA coding for the enzyme phosphoenolpyruvate carboxykinase was examined in H4-II-E cells. this mRNA comprised about 0.1% of total cellular poly(A)+RNA activity in uninduced cells and was increased 5- to 7-fold by the cyclic nucleotide. The maximal level was reached 3 h after addition of the nucleotide to the cell culture. This induction is attributed to cAMP since the nonmetabolizable analogs 8-bromocAMP and 8-(4-chlorophenylthio)cAMP produce inductions comparable to Bt2cAMP while sodium butyrate and dibutyryl cyclic GMP had little effect. The increased translational activity correlated well with a proportionate increase in the amount of phosphoenolpyruvate carboxykinase (P-enolpyruvate carboxykinase) mRNA sequences which were hybridizable to a specific cDNA probe. Blot hybridization of total nuclear RNA isolated from uninduced H4-II-E cells revealed eight P-enolpyruvate carboxykinase RNA sequence species ranging in size from 1.8 to 6.9 kilobases. Treatment with Bt2cAMP increased the amount of all eight of these forms. This increase became maximal by 45-60 min and was maintained for at least 1 h. In contrast, analysis of cytoplasmic RNA showed a single 3.2-kilobase (23 S) band, which was still increasing in amount 2 h after Bt2cAMP treatment. Thus, Bt2cAMP resulted in a sequential induction of nuclear P-enolpyruvate carboxykinase RNA sequences followed by an increase in cytoplasmic phosphoenolpyruvate carboxykinase mRNA. We conclude that cyclic AMP exerts its main effect on P-enolpyruvate carboxykinase induction at the nuclear level.
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PMID:Induction of the messenger ribonucleic acid coding for phosphoenolpyruvate carboxykinase in H4-II-E cells. Evidence for a nuclear effect of cyclic AMP. 629 24

Phosphoenolpyruvate carboxykinase has been implicated by Rognstad (Rognstad, R. (1979) J. Biol. Chem. 254, 1875-1878) as the rate-limiting step for gluconeogenesis from lactate on the basis of a linear Dixon plot (reciprocal rate of gluconeogenesis versus concentration of inhibitor, mercaptopicolinate). We have confirmed this result with isolated hepatocytes incubated in the absence, but not the presence, of bovine serum albumin. Nonlinear plots are likely the result of mercaptopicolinate binding to the albumin. Both norepinephrine and dibutyryl cyclic AMP decreased the slopes and intercepts of the Dixon plots, but a linear relationship was still obtained. When aminooxyacetate inhibited transaminase reactions sufficiently to depress gluconeogenesis, the resulting mercaptopicolinate inhibition plot was still linear in the presence or absence of norepinephrine. Thus, linearity in the Dixon plot does not assure that the enzyme at the site of inhibition is the rate-limiting step for a pathway. Flux through phosphoenolpyruvate carboxykinase does not appear to be hormonally regulated by changes in oxalacetate concentration since this compound was unchanged by norepinephrine or dibutyryl cyclic AMP. Ca2+ enhanced norepinephrine stimulation of gluconeogenesis from asparagine and glutamine and of ureogenesis from glutamine, indicating both mitochondrial and cytosolic sites of action for this hormone. The effects of catecholamines and cyclic AMP were most clearly distinguished by their influence on glutamate concentration when glutamine was the substrate. Dibutyryl cyclic AMP increased, but norepinephrine decreased glutamate. It is possible that decreased glutamate concentration is a reflection of a catecholamine-directed oxidation of mitochondrial NADPH.
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PMID:Catecholamine stimulation of hepatic gluconeogenesis at the site between pyruvate and phosphoenolpyruvate. 630 90

The presence of high phosphoenolpyruvate carboxykinase (EC 4.1.1.32) activity in mouse islet cytosol has been demonstrated. The enzyme was activated by Mn2+ with a Ka of 100 X 10(-6) mol/l. The mean total activity of the Mn2+-stimulated phosphoenolpyruvate carboxykinase in islet cytosol estimated at 22 degrees C with saturating concentrations of the substrates oxaloacetate and ITP was 146 pmol/min per micrograms DNA. Km was calculated to be 6 X 10(-6) mol/l for oxaloacetate and 140 X 10(-6) mol/l for ITP. The islet phosphoenolpyruvate carboxykinase activity was not increased after starvation of the animals for 48 h. Preincubation of the cytosol at 4 degrees C with Fe2+, quinolinate, ATP, Pi, glucose 6-phosphate, fructose 1,6-bisphosphate, NAD+, NADH, oxaloacetate, ITP, cyclic AMP and Ca2+ had no effect on the enzyme activity. However, preincubation of the cytosol at 37 degrees C with ATP-Mg inhibited the Mn2+-stimulated phosphoenolpyruvate carboxykinase activity progressively with time and in a concentration-dependent manner. A similar but weaker inhibitory effect was observed with p[NH]ppA, whereas p[CH2]ppA, ADP, AMP, adenosine and Pi had no effect. It is tentatively suggested that ATP and p[NH]ppA either by adenylation or otherwise affect the interaction between islet phosphoenolpyruvate carboxykinase and the recently discovered Mr = 29000 protein modulator of the enzyme in such a way - perhaps by causing a dissociation between them - that phosphoenolpyruvate carboxykinase loses its sensitivity to Mn2+ activation.
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PMID:Phosphoenolpyruvate carboxykinase in mouse pancreatic islets. ATP-induced changes in sensitivity to Mn2+ activation. 638 41

Mutants of Escherichia coli containing genetic fusions of lacZ to the pck (phosphoenolpyruvate carboxykinase) locus were isolated by using Mu d(lacZ Ampr) bacteriophage. Synthesis of beta-galactosidase in these strains is regulated by cyclic AMP and glucose (catabolite repression). Synthesis of beta-galactosidase by pck-lacZ fusions was induced in log-phase cells growing on gluconeogenic media, was repressed by glucose, and was also induced up to 100-fold at the onset of stationary phase in LB medium. This stationary-phase induction required cyclic AMP and some other unknown regulatory signal.
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PMID:Regulation of transcription of the Escherichia coli phosphoenolpyruvate carboxykinase locus: studies with pck-lacZ operon fusions. 643 12

A mutant of Saccharomyces cerevisiae lacking phosphoenolpyruvate carboxykinase (E.C. 4.1.1.32) was isolated. The mutant did not grow on gluconeogenic sources except glycerol. The mutation was recessive and apparently affected the structural gene of the enzyme. Intracellular levels of metabolites related to the metabolic situation of the enzyme were not significantly affected after transfer of the mutant from a medium with glycerol to a medium with ethanol as carbon source. In these conditions only AMP decreased 3 to 5 times. A search for mutants affected in the other gluconeogenic enzyme, fructose 1,6 bisphosphatase, remained unsuccessful.
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PMID:Isolation and characterization of a mutant of Saccharomyces cerevisiae defective in phosphoenolpyruvate carboxykinase. 675 Dec 58

1. In vitro glucose uptake and glycogen utilization by Hymenolepis microstoma decreased under high oxygen concentrations. 2. 5-Hydroxytryptamine did not stimulate in vitro glucose uptake but did increase glycogen utilizations by H. microstoma. 3. The reduced glucose uptake under high oxygen concentrations (21 and 95%) resulted in a reduction in excretory products. 4. 14CO2-incorporation studies confirmed that, under both 95% O2:5% CO2 and air-minus-CO2 (identical to 21% O2). CO2-fixation by phosphoenolpyruvate carboxykinase (EC 4.1.1.32) was inhibited. 5. The specific activity of hexokinase (EC 2.7.1.1), phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40) was not stimulated by 5-HT. 6. The concentration of ATP required for optimal stimulation of phosphofructokinase activity was 0.67 mM. Activity was further significantly increased by the addition of cAMP and even greater by AMP.
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PMID:5-hydroxytryptamine, glucose uptake, glycogen utilization and carbon dioxide fixation in Hymenolepis microstoma (Cestoda). 681 65

The metabolism of glutamine in resting and concanavalin-A-stimulated lymphocytes was investigated. In incubated lymphocytes isolated from rat mesenteric lymph nodes, the rates of oxygen and glutamine utilization and that of aspartate production were approximately linear with respect to time for 60 min, and the concentrations of adenine nucleotides plus the ATP/ADP or ATP/AMP concentration ratios remained approximately constant for 90 min. The major end products of glutamine metabolism were glutamate, aspartate and ammonia: the carbon from glutamine may contribute about 30% to respiration. When both glucose and glutamine were presented to the cells, the rates of utilization of both substances increased. Evidence was obtained that the stimulation of glycolysis by glutamine could be due, in part, to an activation of 6-phosphofructokinase. Starvation of the donor animal increased the rate of glutamine utilization. The phosphoenolpyruvate carboxykinase inhibitor mercaptopicolinate decreased the rate of glutamine utilization by 28%; the rates of accumulation of glutamate and ammonia were decreased, whereas those of lactate, aspartate and malate were increased. The mitogen concanavalin A increased the rate of glutamine utilization (by about 51%). The rate of [3H]thymidine incorporation into DNA caused by concanavalin A in cultured lymphocytes was very low in the absence of glutamine; it was increased about 4-fold at 1 microM-glutamine and was maximal at 0.3 mM-glutamine; neither other amino acids nor ammonia could replace glutamine.
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PMID:Glutamine metabolism in lymphocytes of the rat. 688 97

With few exceptions, the specific activities of the glycolytic enzymes and the steady-state content of glycolytic and associated intermediates in protoscoleces of the horse (E.g.H) and sheep (E.g.S) strains of Echinococcus granulosus and the closely related E. multilocularis (E.m.) are very similar. Phosphorylase, hexokinase, phosphofructokinase and pyruvate kinase catalyse non-equilibrium reactions and the patterns of activity for pyruvate kinase, phosphoenolypyruvate carboxykinase and malic enzyme are similar in the three organisms. The levels of tricarboxylic acid cycle intermediates in E.g.H., E.g.S. and E.m. are of the same order as those reported in tissues with an active cycle. Each has a complete sequence of cycle enzymes but there are substantial differences between the three parasites with regard to the activity of individual enzymes. The activities of NAD and NADP-linked isocitrate dehydrogenases are significantly lower in E.g.H. than in E.g.S. and particularly in E.m. which suggests that the tricarboxylic acid cycle may play a more important role in carbohydrate metabolism and energy production in the latter parasites. Nevertheless, the three organisms utilize fermentative pathways for alternative energy production, fix carbon dioxide via phosphoenolpyruvate carboxykinase and have a partial reversed tricarboxylic acid cycle. It is speculated that in vivo more carbon will be channelled towards oxaloacetate than pyruvate at the phosphonenolpyruvate branch point. The steady state content of ATP and the ATP/AMP ratios are low in the three organisms, suggesting a low rate of ATP utilization in each.
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PMID:Intermediary carbohydrate metabolism in protoscoleces of Echinococcus granulosus (horse and sheep strains) and E. multilocularis. 707 Aug 45

The onset of transcription and mRNA accumulation of two liver-specific genes, carbamoylphosphate synthase (CPS) and phosphoenolpyruvate carboxykinase (PEPCK) in individual embryonic rat hepatocytes was investigated with in situ hybridization. In vitro CPS and PEPCK mRNAs can be induced prematurely in monolayer cultures of embryonic rat hepatocytes by glucocorticosteroids and cyclic AMP, i.e. the hormones that also regulate the expression of these genes in vivo. Upon exposure to hormones the cultures showed an interhepatocyte heterogeneity in CPS and PEPCK mRNA content. The pattern of accumulation of nuclear CPS mRNA-precursors indicates that this heterogeneity is generated by intercellular differences in the timing of the onset of transcription. However, under induced steady-state conditions the heterogeneity in the hepatocyte population persisted. The degree of heterogeneity is inversely related to the half life of the gene product (i.e. higher for PEPCK than for CPS and higher for mRNAs than for the respective proteins) and to the concentrations of inducing hormones. Accordingly, the interhepatocyte heterogeneity was most pronounced for the nuclear CPS mRNA-precursor. In contrast, no intercellular differences in the rate of degradation of the mRNAs were seen. These observations reveal that although all hepatocytes can and do express the genes, transcription of a gene in a particular cell is a discontinuous process.
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PMID:The expression of liver-specific genes within rat embryonic hepatocytes is a discontinuous process. 751 3

Incubation of fetal hepatocytes from 21-day-old rats with permeant derivatives of cyclic AMP (cAMP) or glucagon, increased the mRNA levels of 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK-2/FBPase-2), L-pyruvate kinase (L-PK) and phosphoenolpyruvate carboxykinase (PEPCK). Contrary to this behavior, adult hepatocytes exhibited a decrease in the PFK-2/FBPase-2 and L-PK mRNA levels when incubated under equivalent experimental conditions. Dexamethasone also increased the PFK-2/FBPase-2 mRNA levels and costimulation of fetal hepatocytes with dexamethasone and a permeant analogue of cyclic AMP enhanced the levels of PFK-2/FBPase-2 mRNA, a situation opposite to that exhibited by adult hepatocytes. Treatment of the hepatocytes with transcriptional and translational inhibitors also produced differential responses in both types of cells. The PFK-2/FBPase-2 mRNA in fetal hepatocytes was more stable than in the adult cells. These results suggest that specific transcriptional factors and regulatory pathways differentially operate in fetal and adult hepatocytes in the control of the responses of carbohydrate metabolism to cAMP.
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PMID:Differential regulation of the expression of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase and pyruvate kinase by cyclic adenosine 3',5'-monophosphate in fetal and adult hepatocytes. 759 43


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