Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.1 (alkaline phosphatase)
 47,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xenopus laevis (Daudin) adult specimens were submitted to hypophysectomy. Although the operation resulted subtotal, it served the purpose of removing the prolactin-producing cells, whereby the involvement of endogenous prolactin in osmoregulation phenomena was excluded. In the operated animals treated with ovine prolactin the following metabolic parameters, which are closely dependent upon interrenal activity, were estimated: 1) intestine alkaline phosphomonoesterase activity (E.C. 3.1.3.1); 2) liver glycogen level; 3) glucose-6-phosphatase (E.C. 3.1.3.9.) and phosphoenolpyruvate carboxykinase (E.C. 4.1.1.32.) in the liver; 4) blood glucose level; 5) blood ammonia and urea levels; 6) carbamoylphosphate synthetase activity in the liver (E.C. 2.7.2.a); 7) muscle sodium and potassium levels. The above metabolic parameters were found to be pressed by subtotal hypophysectomy and after subsequent prolactin treatment showed the tendency to go back to values similar to those of control animals.
 ...
PMID:Biochemical data on subtotally hypophysectomized Xenopus laevis (Daudin) adult specimens treated or not with prolactin. 21 25

In order to evaluate the usefulness of key gluconeogenic enzymes, in relation to the markers commonly used (alkaline phosphatase and gamma-glutamyl transpeptidase) for the diagnose of cholestasis the serum activity of phosphoenolpyruvate carboxykinase, fructose 1,6-bisphosphatase and glucose-6-phosphatase has been measured in rats with bile-duct ligation. Among the gluconeogenic enzymes studied only phosphoenolpyruvate carboxykinase activity increased significantly in the first 48 hours after cholestasis, decreasing thereafter to normal values. Both alkaline phosphatase and gamma-glutamyl transpeptidase activities showed a very significant increase which persisted throughout the experiment. These results seem to indicate that in spite of the high organ specificity of these enzymes they do not appear to be useful for the diagnosis of cholestasis.
 ...
PMID:Evaluation of key gluconeogenic enzymes in experimental biliary obstruction. 198 72

This report outlines an efficient in situ hybridization method for locating specific mRNAs in tissue cryosections using sulfonated cDNA probes. The method involves chemical modification of DNA probes by insertion of a sulfone radical on cytosine residues, which generates a specific epitope. Sulfonated DNA is then detected by using indirect immunochemical procedure. Alternatively, antibodies conjugated to fluorescein or to alkaline phosphatase were used for mRNA detection. In situ hybridization was developed to study aspects of mesophyll and bundle sheath cell differentiation in maize leaves. Our results indicate that phosphoenolpyruvate carboxylase (PEP C) mRNA is restricted to mesophyll cells, and the nucleus-encoded mRNA of the small subunit (SSU) ribulose 1,5-bisphosphate carboxylase (RuBP C) is limited to the cytosol of bundle sheath cells. Thus, using in situ hybridization, we have demonstrated that the differential distribution of PEP C and RuBP C proteins in the two cell types also reflects the location of their mRNAs. These data imply either a tissue-specific transcriptional regulation or a selective mRNA degradation.
 ...
PMID:Detection of phosphoenolpyruvate and ribulose 1,5-bisphosphate carboxylase transcripts in maize leaves by in situ hybridization with sulfonated cDNA probes. 292 20

Phosphoenolthiopyruvate, the analogue of phosphoenolpyruvate in which the bridging oxygen of the phosphate ester is replaced by sulfur, has been synthesized from methyl acrylate and dimethyl (chlorothio)phosphonate. The compound is a substrate for alkaline phosphatase, pyruvate kinase, enolase, and phosphoenolpyruvate carboxylase. Both pyruvate kinase and phosphoenolpyruvate carboxylase convert the compound to thiopyruvate, which is a substrate for lactate dehydrogenase. Phosphoenolpyruvate carboxylase is slowly inactivated by phosphoenolthiopyruvate.
 ...
PMID:Synthesis and study of phosphoenolthiopyruvate. 324 Mar 40

1. The control of exo-beta-N-acetylglucosaminidase (EC 3.2.1.30) production by Bacillus subtilis B growing on a chemically defined medium was studied. 2. The enzyme was repressed during exponential growth by those carbon sources that enter the glycolytic pathway above the level of phosphoenolpyruvate. When exponential growth ceased as a result of low concentrations of the nitrogen, carbon or metal ion components of the medium, the enzyme was formed and its amount could be increased by the addition of cell-wall fragments as inducer. 3. The enzyme was de-repressed and could be induced during exponential growth on non-glycolytic compounds metabolized directly into pyruvate, acetyl-CoA or tricarboxylic acid cycle intermediates. 4. The major difference in the metabolism of the organism utilizing these two groups of compound was the existence of high activities of phosphoenolpyruvate carboxylase required for gluconeogenesis. 5. It is concluded that the de-repression of glucosaminidase occurs when the only principal change detected in the intermediary metabolism of the organism was the presence of high activities of phosphoenolpyruvate carboxylase. 6. When the organism was grown on media containing repressing compounds, the enzyme was only de-repressed on entry of the cells into the initial stages of sporulation, where phosphoenolpyruvate carboxylase activity, even in the presence of excess of glucose, increased in parallel with glucosaminidase, neutral proteinase and alkaline phosphatase activities. 7. These results suggest a strong link, at the level of the tricarboxylic acid cycle, between the control of phosphoenolpyruvate carboxylase and the control of the de-repression of glucosaminidase and sporulation.
 ...
PMID:Control of the production of exo-beta-N-acetylglucosaminidase by Bacillus subtilis B. 419 60

Cyclic-AMP stabilizes phosphoenolpyruvate carboxykinase (GTP) (PEPCK) mRNA against degradation. To investigate the mechanism of this effect, RNA mobility shift assays were used to determine the interaction of cellular proteins with specific domains from the mRNA. We report here the identification of a protein with an affinity for sequences of PEPCK mRNA with a predicted stem-loop structure. RNA-protein complex formation was significantly reduced if the double-stranded RNA probe was preheated to 90 degrees C. The RNA-binding protein did not bind to the hairpin structure of poly(rI)-poly (rC), indicating some degree of sequence specificity and that the RNA-binding protein is not the interferon-induced double-stranded RNA-activated protein kinase. The binding activity was contained in the cytosolic fraction (100,000 x g) of rat hepatoma FTO-2B cells and was significantly enhanced by high concentrations of KCl. Chromatography on an anion exchanger separated the binding activity from a factor which, upon reconstitution, inhibited the interaction with the RNA probe. Incubation of cells with cAMP resulted in a 3-4-fold decrease in the activity of the RNA-binding protein. An inhibition in complex formation was observed with extracts as early as 60 min after exposure of cells to cAMP. Liver extracts from rats starved for 72 h also had reduced binding activity compared to extracts from fed animals. Cellular extracts treated with alkaline phosphatase exhibited an elevated level of complex formation. An analysis by SDS-polyacrylamide gel electrophoresis of the RNA-protein complex after ultraviolet light cross-linking demonstrated that the RNA-binding protein had a molecular mass of approximately 100 kDa. On the basis of these results, we suggest that liver cells contain a protein whose interaction with PEPCK mRNA is regulated by cAMP-dependent phosphorylation and which may be responsible for the cAMP-mediated control of PEPCK mRNA half-life.
 ...
PMID:A cAMP-regulated RNA-binding protein that interacts with phosphoenolpyruvate carboxykinase (GTP) mRNA. 822 67

In cultured rat hepatocytes the degradation of phosphoenolpyruvate carboxykinase mRNA might be regulated by protein(s), which by binding to the mRNA alter its stability. The 3'-untranslated region of phosphoenolpyruvate carboxykinase mRNA as a potential target was used to select RNA-binding protein(s) from rat liver by the use of gel retardation assays. A cytosolic protein was isolated, which bound to the phosphoenolpyruvate carboxykinase mRNA 3'-untranslated region and other in vitro synthesized RNAs. The protein was purified to homogeneity; it had an apparent molecular mass of 400 kDa and consisted of identical subunits with an apparent size of 24.5 kDa. Sequence analysis of a tryptic peptide from the 24.5-kDa protein revealed its identity with rat ferritin light chain. Binding of ferritin to RNA was abolished after phosphorylation with cAMP-dependent protein kinase and was augmented after dephosphorylation with alkaline phosphatase. Weak binding was observed in extracts from okadaic acid-treated cultured hepatocytes compared with untreated cells. Preincubation of ferritin with an anti-phosphoserine or an anti-phosphothreonine antibody attenuated binding to RNA, while an anti-phosphotyrosine antibody generated a supershift indicating that phosphoserine and phosphothreonine but not phosphotyrosine residues were in close proximity to the RNA-binding region. Ferritin is the iron storage protein in the liver. Binding of ferritin to RNA was diminished in the presence of increasing iron concentrations, whereas the iron chelator desferal was without effect. It is concluded that ferritin might function as RNA-binding protein and that it may have important functions in the general regulation of cellular RNA metabolism.
 ...
PMID:Purification of a RNA-binding protein from rat liver. Identification as ferritin L chain and determination of the RNA/protein binding characteristics. 924

Overexpression of bovine growth hormone (bGH) in transgenic (PEPCK-bGH) mice induces resistance to insulin, which is compensated by a major increase in insulin levels. In these animals, hepatic insulin receptors (InsRs) are downregulated while tyrosine kinase activity of wheat germ agglutinin (WGA)-purified InsRs towards exogenous substrates is unexpectedly increased. By normalizing insulinemia, we attempted to determine whether the alterations detected in the early steps of insulin signal transduction are due to exposure to chronically high GH levels or are secondary to hyperinsulinemia. Transgenic PEPCK-bGH animals were treated with a single intraperitoneal administration of streptozotocin (STZ) or were deprived of food for 48 h, to normalize insulin levels. Both fasting and STZ treatment were effective in reducing insulin blood levels to control values or below, while GH levels remained unchanged (STZ treatment) or increased (fasted animals). In the liver of untreated transgenic mice, the number of InsRs as determined by 125I-insulin binding was significantly diminished (65+/-5% and 60+/-6% of normal values in microsomes and solubilized membranes respectively;P<0.01 vs control mice). In treated transgenic mice, the number of InsRs increased to values similar to or slightly higher than those found in normal control mice (STZ-treated: 139+/-26% and 126+/-8%; fasted: 128+/-5% (P<0.05) and 102+/-1.5%, for microsomes and solubilized membranes respectively). Neither treatment altered InsR affinity. InsR concentration in liver as determined by immunoblotting using an antibody against the beta-subunit of the insulin receptor was found to be reduced in transgenic mice (69+/-3% of normal values,P<0.001) and was normalized after both STZ treatment (105+/-4%) and fasting (109+/-4%). Insulin-stimulated autophosphorylation activity of InsRs in transgenic mice was increased (154+/-13%,P<0.01 compared with the control group), essentially normalized by STZ treatment (96+/-14%), and reduced by fasting, to below the values measured in normal control mice (56+/-15%,P<0.05). The potential influence of basal serine/threonine (Ser/Thr) phosphorylation of the InsR beta-subunit on the regulation of the InsRs from transgenic mice was also investigated. The autophosphorylation activity of WGA-purified InsRs from all groups of mice studied was essentially unchanged after dephosphorylation with alkaline phosphatase or mild trypsinization. Consequently, our results suggest that the observed changes in InsR number and autophosphorylation activity in the liver of bGH transgenic mice are directly related to changes in insulin blood levels, and that Ser/Thr phosphorylation is apparently not involved in the regulation of the InsR autophosphorylation activity in this model of insulin resistance.
 ...
PMID:Role of hyperinsulinemia on hepatic insulin receptor concentration and autophosphorylation in the presence of high growth hormone levels in transgenic mice overexpressing growth hormone gene. 979 37

Activating transcription factor 3 (ATF3), a member of the ATF/cAMP-responsive element-binding protein family of transcription factors, is a transcriptional repressor, and the expression of its corresponding gene, ATF3, is induced by many stress signals. In this report, we demonstrate that transgenic mice expressing ATF3 in the liver had symptoms of liver dysfunction such as high levels of serum bilirubin, alkaline phosphatase, alanine transaminase, aspartate transaminase, and bile acids. In addition, these mice had physiological responses consistent with hypoglycemia including a low insulin:glucagon ratio in the serum and reduced adipose tissue mass. Electrophoretic mobility shift assays indicated that ATF3 bound to the ATF/cAMP-responsvie element site derived from the promoter of the gene encoding the gluconeogenic enzyme phosphoenolpyruvate carboxykinase (PEPCK). Furthermore, transient transfection assays indicated that ATF3 repressed the activity of the PEPCK promoter. Taken together, our results are consistent with the model that the expression of ATF3 in the liver results in defects in glucose homeostasis by repressing gluconeogenesis. Because ATF3 is a stress-inducible gene, these mice may provide a model to investigate the molecular mechanisms of some stress-associated liver diseases.
 ...
PMID:The roles of ATF3 in liver dysfunction and the regulation of phosphoenolpyruvate carboxykinase gene expression. 1191 68

Insulin is the key hormone that controls glucose homeostasis. Dysregulation of insulin function causes diabetes mellitus. Among the two major forms of diabetes, type 2 diabetes accounts for over 90% of the affected population. The incidence of type 2 diabetes is highly related to obesity. To find novel proteins potentially involved in obesity-related insulin resistance and type 2 diabetes, a functional expression screen was performed to search for genes that negatively regulate insulin signaling. Specifically, a reporter system comprised of the PEPCK promoter upstream of alkaline phosphatase was used in a hepatocyte cell-based assay to screen an expression cDNA library for genes that reverse insulin-induced repression of PEPCK transcription. The cDNA library used in this study was derived from the white adipose tissue of ob/ob mice, which are highly insulin-resistant. The mitogen-activated dual specificity protein kinase phosphatase 4 (MKP-4) was identified as a candidate gene in this screen. Here we show that MKP-4 is expressed in insulin-responsive tissues and that the expression levels are up-regulated in obese insulin-resistant rodent models. Heterologous expression of MKP-4 in preadipocytes significantly blocked insulin-induced adipogenesis, and overexpression of MKP-4 in adipocytes inhibited insulin-stimulated glucose uptake. Our data suggest that MKP-4 negatively regulates insulin signaling and, consequently, may contribute to the pathogenesis of insulin resistance.
 ...
PMID:Dual specificity mitogen-activated protein (MAP) kinase phosphatase-4 plays a potential role in insulin resistance. 1277 78


1 2 3 Next >>