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 lowering the liver pyridoxal phosphate (PLP) concentration by vitamin B-6 deficiency on the stability of several rat liver enzymes were examined. Three PLP-dependent enzymes (serine dehydratase, ornithine-delta-aminotransferase, and tyrosine aminotransferase) and two non-PLP-dependent enzymes (glucose-6-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase) were induced in vitamin B-6 deficient and control rats by feeding them high-protein diets or by injecting them with glucagon or dexamethasone. The decline of each activity was followed after withdrawal of the inducer. Serine dehydratase activity declined more rapidly in vitamin B-6 deficient than in control liver; however, ornithine aminotransferase and tyrosine aminotransferase activities were equally stable in deficient and control liver. Ornithine aminotransferase was predominantly in holoenzyme form in both control and deficient rats, whereas tyrosine aminotransferase was predominantly in apoenzyme form in both groups. The proportion of serine dehydratase in apoenzyme was less stable than the holoenzyme. Activity changes of glucose-6-phosphate dehydrogenase and phosphoenolpyruvate carboxykinase in control and vitamin B-6 deficient rats were similar. The results suggest that differences in the stability of PLP-dependent enzymes in vitamin B-6 deficient rats depend upon differences in the proportions of these enzymes existing as holo- and apoenzyme.
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PMID:Stability of some pyridoxal phosphate-dependent enzymes in vitamin B-6 deficient rats. 0 99

In alloxan diabetic rats a stimulatory effect of stress on the activity of liver phosphoenolpyruvate carboxykinase seems to be very likely. In intact animals the inhibitory effect of glucose feeding (15% glucose instead of laboratory diet and water) on the activity of liver tyrosine aminotransferase (TAT) and tryptophan pyrrolase was reconfirmed. Moreover, a reversal of this effect by immobilization for 2.5 h was observed. After a mean intake of 5.3 g glucose/100 g body weight during 16 h this reversal was only partial and after 3.4 glucose/100 g during the same time the glucose effect was abolished. Stimulation of both enzymes by corticosterone and of TAT by stress-induced release of glucagon may play a role in this reversal.
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PMID:Inhibitory effect of immobilization stress on depression of liver tyrosine aminotransferase and tryptophan pyrrolase by glucose feeding in rats. 1 21

In adult male rats kept under controlled illumination (lights on from 6 a.m.--6 p.m.) the existence of higher afternoon values of plasma corticosterone ("B") is reconfirmed. Moreover, plasma "B" increases induced by 400 revolutions in Noble-Collip drums or immobilization for 2.5 h were found substantially less pronounced if stressor application took place at 4 p.m. rather than 8 a.m. so that essentially no difference between morning and afternoon poststress peaks was observed. Also the response to 0.05 mg ACTH i.p. was smaller in the afternoon experiments. Additionally three liver enzymes the activity of which is increased by corticosterone released under conditions of stress were also studied. Higher afternoon activity of liver tyrosine aminotransferase (TAT) and tryptophan pyrrolase (TP) was observed in spite of fasting from 8 a.m. imposed to the animals taking part in the afternoon experiments. The activity of phosphoenolpyruvate carboxykinase (PEPCK) was also increased in the afternoon probably because of the food deprivation. Immobilization-induced increase in the activity of all three enzymes showed a similar blunting as plasma "B" response, so that no differences between morning and afternoon were found in peak poststress values. In conclusion, the low plasma "B" response of rats at a time when the animals begin the active part of their day seems to have important metabolic implications.
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PMID:A three hours study of the response of plasma corticosterone and of three liver enzymes in rats subjected to stress in the late afternoon or during the morning hours. 3 35

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

A variety of 6- and 8-substituted analogs of cAMP (cyclic adenosine 3:5-monophosphate) have been tested for their ability to increase activity of tyrosine aminotransferase (EC 2.6.1.5) in cultured Reuber H35 hepatoma cells. Some analogs, particularly the 8-thio-substituted ones, produced effects approximately equivalent to those generated by N-6, O2'-dibutyryl cAMP. In contrast, cAMP and its O-2-monobutyryl derivative were relatively ineffective even at very high concentrations, whereas three other analogs actually depressed the activity of the aminotransferase. Changes in enzyme activity generated by the various analogs were paralleled closely by changes in the relative rate of aminotransferase synthesis. An excellent correlation was found to exist between the ability of any given analog to influence the activity of tyrosine aminotransferase and that of phosphoenolpyruvate carboxykinase (EC 4.1.1.32). A similar correlation was found to exist between the ability of various analogs to evelate the activity of these enzymes and to inhibit reversibly the growth of H35 cells. Only one of five inhibitors of cAMP phosphodiesterase activity tested produce any increase in aminotransferase activity when added alone. All of the 6- and 8-substituted analogs tested, including noniducers, stimulated f1 histone phosphorylation in crude rat liver extracts with approximately equal potencies. On the other hand, dibutyryl cAMP was only a weak activator of protein kinase in vitro, even though it is a potent enzyme inducer. A possible resolution of this apparent discrepancy has been provided by preliminary analyses of site-specific f1 histone phosphorylation in whole cells. Only compounds active as aminotransferase inducers are capable of stimulating phosphorylation of the serine-37 residue of endogenous f1 histone (3- to 10-fold).
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PMID:Effects of 6- and 8-substituted analogs of adenosine 3':5'-monophosphate on phosphoenolpyruvate carboxykinase and tyrosine aminotransferase in hepatoma cell cultures. 23 87

The phosphoenolpyruvate carboxykinase (PEPCK) gene is highly expressed in cultured rat hepatoma cells, but extinguished in hepatoma x fibroblast hybrids. Extinction of PEPCK gene expression in hybrids is a polygenic process that involves several fibroblast loci, only one of which (tissue-specific extinguisher-1, TSE1) has been characterized to date. To identify sequence elements of the PEPCK gene that are involved both in TSE1-mediated extinction and in TSE1-independent processes, we assayed expression of chimeric PEPCK transgenes in transiently and stably transfected hybrid cells. We report that TSE1 responsiveness mapped to the PEPCK CRE (cAMP response element), as shown previously for the tyrosine aminotransferase gene. This was expected from the recent identification of the TSE1 gene product as a regulatory subunit of protein kinase A. However, none of the transgenes we assayed were responsive to TSE1-independent extinction mechanisms, suggesting that these controls require DNA sequences and/or chromatin structures that were not present in the transfected reporters. The implications of these findings are discussed.
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PMID:Multiple elements regulate phosphoenolpyruvate carboxykinase gene expression in hepatoma hybrid cells. 133 26

Cyclic AMP treatment of hepatoma cells leads to increased protein binding at the cyclic AMP response element (CRE) of the tyrosine aminotransferase (TAT) gene in vivo, as revealed by genomic footprinting, whereas no increase is observed at the CRE of the phosphoenolpyruvate carboxykinase (PEPCK) gene. Several criteria establish that the 43 kDa CREB protein is interacting with both of these sites. Two classes of CRE with different affinity for CREB are described. One class, including the TATCRE, is characterized by asymmetric and weak binding sites (CGTCA), whereas the second class containing symmetrical TGACGTCA sites shows a much higher binding affinity for CREB. Both classes show an increase in binding after phosphorylation of CREB by protein kinase A (PKA). An in vivo phosphorylation-dependent change in binding of CREB increases the occupancy of weak binding sites used for transactivation, such as the TATCRE, while high affinity sites may have constitutive binding of transcriptionally active and inactive CREB dimers, as demonstrated by in vivo footprinting at the PEPCK CRE. Thus, lower basal level and higher relative stimulation of transcription by cyclic AMP through low affinity CREs should result, allowing finely tuned control of gene activation.
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PMID:Phosphorylation of CREB affects its binding to high and low affinity sites: implications for cAMP induced gene transcription. 135 12

The present study investigates the effect of glucose on the gene expression of the hepatic glucoregulatory enzyme, phosphoenolpyruvate carboxykinase (PPrvck). By use of hepatocytes in culture and FAO hepatoma cells it could be demonstrated that glucose suppressed the effect of dibutyryl cyclic AMP (Bt2cAMP), glucocorticoids or both, to increase PPrvck mRNA and consequently PPrvck enzyme activity. Glucose had a dual effect; it reduced PPrvck gene transcription and it accelerated the rate of PPrvck mRNA degradation. The effect was specific for glucose, as glucose-related carbohydrates such as mannose, galactose and sorbitol were without effect on PPrvck mRNA. The repressive effect of glucose was limited to certain proteins; glucose had no effect on Bt2cAMP and glucocorticoid provoked induction of tyrosine aminotransferase (TAT). Also the pattern of mRNA in vitro translation products was virtually unaffected when FAO hepatoma cells were incubated either in the presence or absence of glucose, demonstrating the specificity of the effect of glucose on gene expression of selected proteins. In FAO hepatoma cells and in hepatocytes in culture, insulin, like glucose, also decreased PPrvck mRNA. While the effect of glucose and insulin was additive in FAO hepatoma cells, in primary hepatocytes in culture an effect of glucose by itself on PPrvck mRNA could only be demonstrated in the absence of insulin. Correspondingly also in vivo, the effect of glucose was demonstrated in the absence of insulin (provoked by streptozotocin diabetes); glucose application reduced the amount of hepatic PPrvck mRNA. To summarize, glucose is capable of suppressing the effect of glucocorticoids and Bt2cAMP on increasing the PPrvck mRNA level. The carbohydrate reduces the rate of PPrvck gene transcription and accelerates the rate of PPrvck mRNA degradation. While in FAO hepatoma cells the effect is evident in the presence of insulin, in hepatocytes in culture the effect of glucose cannot be demonstrated in the presence of insulin, questioning its role under physiological conditions.
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PMID:Transcriptional and post-transcriptional effects of glucose on liver phosphoenolpyruvate-carboxykinase gene expression. 166 21

Chronic alcoholism is frequently associated with impaired intermediary metabolism and insulin resistance. The cellular defects leading to insulin resistance have not been clearly defined but could result from reduced insulin binding or abnormalities in any one of several postreceptor steps. The purpose of the present studies was to measure 125I-insulin binding and internalization kinetics and postreceptor response of the enzyme activity of tyrosine aminotransferase in isolated cultured rat hepatocytes. Four weeks of alcohol ingestion significantly reduced to 47% of control the 125I-insulin binding sites measured either as surface or total (after digitonin permeabilization). In contrast, 125I-epidermal growth factor binding was not significantly changed. Internalization of surface-bound 125I-insulin was decreased, but degradation was not increased, indicating that altered kinetics did not account for the change. Ethanol ingestion markedly reduced in liver cytosol some enzymes regulated by insulin and involved in glucose homeostasis. Basal activities of tyrosine aminotransferase and glucokinase were reduced 51% (P less than 0.01) and 32% (P less than 0.01), respectively. In contrast, phosphoenolpyruvate carboxykinase was unchanged. In short-term cultured hepatocytes from ethanol-fed rats, the maximum response of tyrosine amino-transferase to insulin was reduced 40% (P less than 0.01) without a change in the concentration causing 50% of the maximum response (EC50) compared with controls. In contrast, dexamethasone increased tyrosine aminotransferase to similar maximal levels and with similar EC50, indicating that ethanol did not alter the intracellular response. In conclusion, chronic ethanol ingestion caused significant time-dependent and selective changes in cell surface binding of insulin that was associated with subsequent postreceptor events.
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PMID:Impairment of hepatic insulin receptors during chronic ethanol administration. 167 84

Mice homozygous for chromosomal deletions at or around the albino locus on chromosome 7 express reduced levels of a group of liver genes, including tyrosine aminotransferase (TAT) and phosphoenolpyruvate carboxykinase (PEPCK), and generally die perinatally. Sequences within the deleted region are thought to encode a regulatory factor(s) that affects expression of these genes in trans. To facilitate study of the putative factors, we immortalized hepatocytes derived from newborn cch wild-type and c14CoS deletion homozygous mice as well as cch/c14CoS heterozygous mice using a SV40 temperature-sensitive A255 mutant virus. Three c14CoS deletion homozygous hepatocyte lines were characterized and compared with the homozygous wild-type and heterozygous lines. The SV40 tsA255 mutant-transformed hepatocyte lines were temperature-sensitive for maintenance of transformation and expressed many liver-specific genes. In agreement with in vivo studies, hepatocyte lines derived from mice homozygous for the deletion expressed reduced mRNA levels of a number of liver genes including TAT, PEPCK, X1, X2, and X7 in comparison with heterozygous and wild-type cell lines. Similar mRNA levels of transferrin and albumin, genes whose expression is unaffected by the mutation in vivo, were observed in all cell lines. The expression of two genes, X5 and metallothionein, reported to be reduced in newborn mutant mice, did not differ appreciably among cell lines. TAT and PEPCK have been shown to respond poorly to glucocorticoids and cAMP in newborn mutant mice. Interestingly, all affected liver genes tested were responsive to glucocorticoids and dibutyryl cAMP in deletion homozygous cell lines as well as in wild-type and heterozygote-derived cell lines. This may suggest that effects of the deletion on expression of liver-specific genes do not cause loss of responsiveness to glucocorticoids and cAMP. These immortalized hepatocyte lines, which express most, if not all, liver-specific genes, should provide a useful means for further investigation of the effects of the albino lethal deletion.
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PMID:Isolation and characterization of mouse hepatocyte lines carrying a lethal albino deletion. 184 57


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