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 effects of chronic oral ingestion of lead in doses ranging from 20-80 ppm were compared with those seen after the subacute exposure of rats to a 10 mg/kg daily dose of the heavy metal for 7 days. Irrespective of the treatment regimen used, lead treatment significantly increased the activities of renal pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose 1,6-diphosphatase and glucose 6-phosphatase. The observed enhancement of kidney gluconeogenic enzymes in chronically treated animals was associated with a stimulation of the adenylate cyclase-cyclic AMP system, a rise in blood blucose and urea as well as a depression in hepatic glycogen and serum immunoreactive insulin (IRI) levels. In contrast, subacute exposure to lead failed to significantly alter cyclic AMP metabolism and the concentrations of liver glycogen, blood glucose, serum urea or IRI. Whwereas the insulinogenic index (the ratio of serum IRI to blood glucose concentration) was markedly suppressed in chronically treated rats, this ratio remained within normal limits following subacute exposure to the heavy metal. However, a marked decrease in the insulinogenic index was observed in subacutely treated rats 15 min after the administration of a glucose load. The data provide evidence to show that increased glucose synthesis as well as suppressed pancreatic function may be responsible for lead-induced disturbances in glucose homeostasis.
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PMID:Effects of subsacute and chronic lead treatment on glucose homeostasis and renal cyclic AMP metabolism in rats. 18 14

In different metabolic states renal phosphoenolpyruvate carboxykinase (PEP-CK) activities are closely correlated with in vitro glucogenic rates, suggesting a limitation of the glucogenic capacity of kidney by this enzyme. Stimulation of renal gluconeogenesis from pyruvate, lactate, and succinate by lysine and glutamine was therefore associated with a regulatory attack of these amino acids at the level of PEP-carboxykinase. This postulate was confirmed by the failure of lysine to stimulate glucose synthesis from fructose. Experimental support for an interference of glutamine and PEP-carboxykinase was obtained by a study on the inactivation of this enzyme in kidney cortex homogenates: A rapid inactivation of enzyme activity within 40-50 min could be slowed down by glutamine. In addition the inactivation was counteracted by ATP. At suboptimal concentrations of the trinucleotide its effect was potentiated by c-AMP and c-GMP. Studies on the effect of ATP on PEP-carboxykinase in kidney cortex homogenates from rats in different metabolic states revealed: In homogenates from carbohydrate fed animals extreme low activities of PEP-CK were not altered by ATP, whereas elevated enzyme activities after a protein rich diet could be further raised by a factor of 2 or 3 by ATP. GTP and ITP could substitute for ATP. An extension of these studies on hepatic enzymes showed a similar inactivation of tyrosine aminotransferase (TAT) and a protective effect of ATP. The data obtained from these experiments favour an interconversion of PEP-carboxykinase and tyrosine aminotransferase into different forms as possible mechanism for their regulation.
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PMID:Regulation of phosphoenolpyruvate carboxykinase by glutamine and ATP as possible control mechanisms of renal gluconeogenesis. 18 82

The mechanism of the interaction between glucocorticoids and cyclic AMP in the regulation of phosphoenolpyruvate carboxykinase (GTP: oxalocetate carboxylase, transphosphorylating, EC 4.1.1.32) was investigated in the isolated perfused rat liver using inhibitors of transcription or translation. Dibutyryl cyclic AMP produced a rapid increase in P-enolpyruvate carboxykinase activity. The response of the enzyme to the cyclic nucleotide ceased however, at 4 h, but was restored by dexamethasone. The dibutyryl cyclic AMP-induced increase in P-enolpyruvate carboxykinase activity was completely blocked by cycloheximide, but not not by cordycepin. However, cordycepin totalaly suppressed the "permissive" effect of dexamethasone on the response of the enzyme to dibutyryl cyclic AMP. Preperfusion of the livers with dexamethasone and cycloheximide, following by perfusion without the steroid hormone and the inhibitor, resulted in a rapid rise in P-enolpyruvate carbosykinase activity, which was not affect by cordycepin. If livers were preperfused with cordycepin for different time-periods, followed by dibutyryl cyclic AMP stimulation of P-enolpyruvate carboxykinase synthesis, the response of the enzyme to the cyclic nucleotide was progressively reduced, achieving 50% inhibition after 1.5 h of preperfusion. These results suggest that the induction of hepatic P-enolpyruvate carboxykinase to maximum values, brought about by cyclic AMP at the level of translation, depends on the supply of newly synthetized mRNA provided by the transcriptional action of glucocorticoids.
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PMID:Interaction between glucocorticoids and cyclic AMP in the regulation of phosphoenolpyruvate carboxykinase (GTP) in the isolated perfused rat liver. Effects of cordycepin and cycloheximide. 18 61

The administration of N6, O2'-dibutyryl cyclic AMP and theophylline to fasted-refed rats produces an 8-fold stimulation of the relative rate of hepatic phosphoenolpyruvate carboxykinase synthesis in 90 min, as measured by isotopic immunochemical techniques in vivo. The mechanism of this induction was studied first by using a homologous, noninitiating cell-free protein-synthesizing system derived from the liver of fasted-refed, cyclic AMP-treated rats. In such a system, a 5-fold increase in phosphoenolpyruvate carboxykinase synthseis is observed at 20 min post-treatment and a 9-fold stimulation at 75 min, indicating a rapid increase in the number of ribosomes engaged in the translation of the enzyme mRNA after exposure to cyclic AMP. The level of functional mRNA coding for phosphoenolpyruvate carboxykinase was then assayed in a wheat germ protein-synthesizing system capable of using rat liver mRNA as template. The template activity for phosphoenolpyruvate carboxykinase synthesis is greatly increased in the poly(A)-containing RNA isolated from cyclic AMP-induced animals. Both the increase in the capacity of the liver extract for in vitro phosphoenolpyruvate carboxykinase synthesis and the emergence of enzyme mRNA detected in the wheat germ assay are completely prevented by a pretreatment with cordycepin at doses which inhibit the appearance in the cytoplasm of newly synthesized poly(A)-containing RNA. These data demonstrate that the induction of hepatic phosphoenolpyruvate carboxykinase by cyclic AMP is characterized by the rapid build-up of newly synthesized, actively translated mRNA coding for the enzyme. The messenger accumulation could be due to an increase in the rate of its production or a decrease in the rate of its degradation.
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PMID:Increase in level of functional messenger RNA coding for phosphoenolpyruvate carboxykinase (GTP) during induction by cyclic adenosine 3':5'-monophosphate. 18 22

The effect of re-feeding glucose, protein or fat and the effect of insulin injection on the activity of hepatic phosphoenolpyruvate carboxykinase (GTP: oxaloacetate carboxy-lyase (transphosphorylating) EC 4.1.1.32), the concentration of hepatic cyclic AMP and the level of serum insulin was investigated in starved rats. Under all conditions examined the concentration of serum insulin was elevated to a high degree. However, only rats re-fed with glucose responded to the increase in serum insulin with a decrease in PEP carboxykinase activity, while the activity of the enzyme remained unchanged or was elevated after re-feeding protein or fat or after insulin injection, respectively. Since under all conditions there was a close correlation between cyclic AMP concentration and PEP carboxykinase activity, but not between the insulin level and enzyme activity, it is concluded that the hormone physiologically regulates PEP carboxykinase activity by decreasing the intrahepatic cyclic AMP concentration rather than by the postulated cyclic AMP-independent inhibition of specific mRNA translation.
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PMID:Physiological regulation of rat liver phosphoenolpyruvate carboxykinase (GTP) by insulin. Insignificance of a cyclic AMP-independent mechanism. 19 43

Phosphoenolpyruvate carboxykinase (GTP) [GTP;oxaloacetate carboxy-lyase(transphosphorylating); EC 4.1.1.32] is absent in rat liver cytosol during fetal life and is synthesized initially at birth. De novo synthesis of the enzyme can be induced prematurely by injection of dibutyryl cyclic AMP or glucagon into fetal animals in utero. In this study a wheat germ translation assay was used to quantitate the level of total functional mRNA for phosphoenolpyruvate carboxykinase in the liver of fetal rats at 21 days of pregnancy under different induction situations. The translatable mRNA for the enzyme was marginally detectable in fetal rat liver. Administration of either glucagon or dibutyryl cyclic AMP to fetal rats in utero caused a marked induction of functional mRNA for this enzyme. Three hours after administration of dibutyryl cyclic AMP, the level of translatable mRNA increased almost 23-fold, but by 6 hr the level dropped approximately 60%. Administration of actinomycin D prior to dibutyryl cyclic AMP in 21-day fetal rats prevented the appearance of newly synthesized poly(A)-containing RNA in the cytoplasm as well as the induction of translatable mRNA for phosphoenolpyruvate carboxykinase. In animals delivered prematurely and maintained for varying periods, the translatable mRNA for the enzyme accumulated in the liver at a rate comparable to that observed for enzyme synthesis.
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PMID:Changes in hepatic messenger RNA for phosphoenolpyruvate carboxykinase (GTP) during development. 21 40

The mRNA coding for the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) was partially purified from the liver of cyclic-AMP-treated rats by a procedure involving multiple oligo(dT)-cellulose chromatographies and sucrose gradient fractionations. The purification was monitored by translational assay using a wheat germ extract. Relative to RNA bound once to oligo(dT)-cellulose, the final material was enriched 20-fold in template activity for phosphoenolpyruvate carboxykinase synthesis. With this RNA preparation, cell-free enzyme synthesis amounted to 5% of total mRNA-directed protein synthesis. The apparent sedimentation coefficient of phosphoenolpyruvate carboxykinase mRNA in sucrose gradients was between 20 and 22 S, corresponding to an average molecular weight of 0.93 X 10(6). By formamide/polyacrylamide gel electrophoresis the molecular weight of the enzyme mRNA was estimated at between 0.91 X 10(6) and 1.12 X 10(6). From these estimates, it was concluded that considerable non-coding sequence(s) are present in the mRNA. Approximately 20% of the enzyme mRNA in rat liver failed to bind to oligo(dT)-cellulose, presumably because of the absence of a poly(A) segment. The translation of phosphoenolpyruvate carboxykinase mRNA by the wheat germ extract was inhibited in the presence of 7-methylguanosine 5'-phosphate. The enzyme mRNA appears therefore to have a 'cap' at the 5' end.
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PMID:Partial purification and characterization of rat-liver messenger RNA coding for phosphoenolpyruvate carboxykinase (GTP). 21 68

Mitochondria of cultured normal human fibroblast cells were found to contain the enzyme phosphoenolpyruvate carboxykinase. The activity of this enzyme in these cells is increased 2- to 3-fold by addition of 5 . 10(-4) M dibutyryl cyclic AMP, or 1.5- to 2-fold by the addition of dexamethasone (2 . 10(-7) M) or hydrocortisone (1.38 . 10(-6) M). These increases in enzyme activity were inhibited cycloheximide and actinomycin D, suggesting they are dependent upon de novo protein synthesis. Cultured human fibroblasts may thus provide a useful system for studying the regulation of mitochondrial phosphoenolpyruvate carboxykinase.
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PMID:Induction of mitochondrial phosphoenolpyruvate carboxykinase in cultured human fibroblasts. 21 92

Endotoxin-stimulated glucocorticoid-antagonizing factor (GAF) was assayed by its specific inhibition of hydrocortisone-induced synthesis of phosphoenolpyruvate carboxykinase. Defined induction of phosphoenolpyruvate carboxykinase synthesis in hydrocortisone-treated rat hepatoma cells permitted reliable quantitation of GAF and analysis of the mechanism of cortisol antagonism. GAF was present maximally in serum 2 hours after endotoxin challenge in mice; however, GAF production could be suppressed by pretreating mice with indomethacin or cortisol. Endotoxin-tolerant mice were also nonresponsive to endotoxin-stimulated GAF production. Gel filtration on Sephadex G-200 resolved four regions of glucocorticoid-antagonizing activity in serum from endotoxin-poisoned mice, two of which were not present in normal serum. Cortisol antagonism by GAF resembled that of insulin; however, insulin differed from GAF in its ability to antagonize dibutyryl cyclic AMP. Unlike insulin, endotoxin-induced serum glucocorticoid-antagonizing activity was heat-labile at 70 degrees C. GAF antagonism of hydrocortisone was partially reversible but did not act in a competitive manner. Production of hepatoma growth inhibitory activity and glucocorticoid-antagonizing activity in serum were closely associated, indicating a common methanism for their generation.
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PMID:The use of Reuber hepatoma cells for the study of a lipopolysaccharide-induced macrophage factor: glucocorticoid-antagonizing factor. 45 33

Gluconeogenesis by isolated hepatocytes resulted in glucose release but insignificant rates of glycogen synthesis. The effectiveness of precursors was similar for hepatocytes from fed and starved chickens except for impaired gluconeogenesis from pyruvate when compared to lactate in lactate starved chicken hepatocytes. The impairment was caused by limitations in cytosolic NADH production as a result of the mitochondrial location of phosphoenolpyruvate carboxykinase in chicken liver. The order of effectiveness of precursors on hepatic gluconeogenesis was generally similar to the effects of precursors on increasing the plasma glucose concentration in vivo. The exceptions were caused by interactions with other precursors in vivo. The alteration of the NADH/NAD+ ratio by ethanol and ATP/ADP ratio by adenosine could play significant roles in the control of precursor conversion to glucose. Physiological glucagon concentrations stimulated gluconeogenesis from precursors entering the pathway both above and below the level of triose phosphates, and its effect were mimicked by dibutyryl cyclic AMP. Previous results on the effects of precursor and glucagon injection on the plasma glucose concentration of chickens in vivo can largely be explained by effects at the hepatic level. Isolated chicken and rat hepatocytes share many common features. Qualitatively the ordering of gluconeogenic effectiveness was similar but quantitive differences existed as a result of differing activities and cellular locations of enzymes. Neither preparation readily synthesised glycogen and the sensitivity to glucagon was similar.
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PMID:Hepatic gluconeogenesis in chickens. 74 98


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