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:3.1.3.9 (glucose-6-phosphatase)
3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have utilized S-farnesyl-Leu-Ala-Arg-Tyr-Lys-Cys as a methyl-accepting substrate to characterize a membrane-bound C-terminal protein methyltransferase from rat liver. We have localized the activity to the microsomal fraction and show that the bulk of the enzyme fractionates by density gradient centrifugation with glucose-6-phosphatase, a marker of the endoplasmic reticulum, and not with 5'-nucleotidase, a marker of the plasma membrane, or galactosyl:N-acetylglucosamine transferase, a marker of the Golgi apparatus. This methyltransferase appears to form an integral part of the membrane structure. Its activity is markedly affected by a variety of detergents used to solubilize membrane proteins in their native form. All activity is lost when membranes are treated with seven different detergents at a concentration of 1% (w/v). The activity is inhibited by N-ethylmaleimide, although it can be protected against inactivation with its substrate S-adenosyl-L-methionine, or its product S-adenosyl-L-homocysteine. Finally, we find that 5'-methylthioadenosine, a substrate analogue reported to be an inhibitor of this activity in other studies, is not an effective inhibitor in vitro.
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PMID:Characterization of a rat liver protein carboxyl methyltransferase involved in the maturation of proteins with the -CXXX C-terminal sequence motif. 132 16

Intramuscular injections of the title drug in a dose of 5 mg/kg (5% of the LD50) during 10 days produced in the liver and blood serum of white rats a decrease in the activity of glucokinase, succinate dehydrogenase, glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, glutathione reductase, ATPase and ceruloplasmin. The urea content in total phospholipids rose, whereas the content of triglycerides and hexosamine diminished. Ten and 20 days after the drug was discontinued the majority of these characteristics returned to normal. The activity of glucosophosphate isomerase, transketolase, glucose-6-phosphatase, fructose-1,6-diphosphatase and lactate dehydrogenase as well as the content of total cholesterol, free fatty acids, tyrosine, hydroxyproline, total protein, RNA and DNA remained unchanged.
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PMID:[Effect of decane-1,10-bis[acetoxy-(N, N)-dimethyl-(N)-(diphenylmethoxy-2-ethyl) ammonium] dichloride on metabolism in white rats]. 651 57

The plasma levels of corticosterone, insulin and glucagon, and the concomitant changes in the levels of several liver enzymes and metabolites were measured in intact rats in the basal state during 24 hours and under conditions of food deprivation and hypoxia. The levels of the following enzymes and metabolites were examined: phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, pyruvate kinase, phosphofructokinase, glutamic-oxaloacetic transaminase, glutamic-pyruvic transaminase, glucose, glucose-6-phosphate, glycogen, fructose-6-phosphate, hexokinase, tyrosine amino-transferase and tryptophan oxygenase. During food deprivation, the increased gluconeogenesis is possibly a result of glucagon activity. In contrast, however, during hypoxia the increase in gluconeogenesis seems to be a result of the higher plasma level of corticosterone. During starvation, the insulin concentration dropped steadily and came close to zero.
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PMID:Plasma concentrations of glucose, corticosterone, glucagon and insulin and liver content of metabolic substrates and enzymes during starvation and additional hypoxia in the rat. 703 Aug 99

The present investigation was undertaken to characterize the direct inhibitory action of the peroxyvanadium compounds oxodiperoxo(1, 10-phenanthroline) vanadate(V) (bpV(phen)) and oxodiperoxo(pyridine-2-carboxylate) vanadate(V) (bpV(pic)) on pig microsomal glucose-6-phosphatase (G-6-Pase) activity and on glucagon stimulated hyperglycemia in vivo. Both bpV(phen) and bpV(pic) were found to be potent competitive inhibitors of G-6-Pase with Ki values of 0.96 and 0.42 microM (intact microsomes) and 0.50 and 0.21 microM (detergent-disrupted microsomes). The corresponding values for ortho-vanadate were 20.3 and 20.0 microM. Administration of bpV(phen) to postprandial rats did not affect the basal glucose level although a modest and dose-dependent increase in plasma lactate levels was seen. Injection of glucagon raised the plasma glucose level from 5.5 mM to about 7.5 mM in control animals and this increase could be prevented dose-dependently by bpV(phen). The inhibition of the glucagon-mediated blood glucose increase was accompanied by a dose-dependent increase in plasma lactate levels from 2 mM to about 11 mM. In conclusion, the finding that vanadate and bpV compounds are potent inhibitors of G-6-Pase suggests that the blood-glucose-lowering effect of these compounds which is seen in diabetic animals may be partly explained by a direct effect on this enzyme rather than, as presently thought, being the result of inhibition of phosphoprotein tyrosine phosphatases and thereby insulin receptor dephosphorylation.
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PMID:Peroxyvanadium compounds inhibit glucose-6-phosphatase activity and glucagon-stimulated hepatic glucose output in the rat in vivo. 1033 63

Liver development is regulated by soluble factors as well as cell-cell contacts. We previously reported that oncostatin M (OSM) induced hepatic maturation in a primary culture of embryonic day 14 liver cells. While OSM expression in the liver starts in mid gestation and decreases in postnatal stages, hepatocyte growth factor (HGF) is mainly expressed in the liver in the first few days after birth. In this study, we compared the effect of OSM and HGF on the differentiation of fetal hepatic cells in vitro. Like OSM, HGF in the presence of dexamethasone induced expression of glucose-6-phosphatase, tyrosine amino transferase and carbamoyl-phosphate synthase, and accumulation of glycogen in fetal hepatic cells, although to a lesser extent than OSM. Interestingly, while both OSM and HGF up-regulated production of albumin, secretion of albumin occurred only in response to OSM. In addition, although hepatic maturation induced by OSM depends on STAT3, HGF failed to activate STAT3 and HGF-induced differentiation was independent of STAT3. These results indicate that OSM and HGF induce hepatic maturation through different signaling pathways.
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PMID:Oncostatin M and hepatocyte growth factor induce hepatic maturation via distinct signaling pathways. 1124 43

Previously, we described that embryonic day 14.5 (E14.5) mouse fetal hepatocytes differentiate to express tyrosine amino transferase (TAT) and glucose-6-phosphatase, which are expressed in the perinatal liver, in response to oncostatin M (OSM) or in high-cell-density culture. However, under such conditions, fetal hepatic cells failed to express genes for adult liver-specific enzymes, such as tryptophan oxygenase (TO). Although phenobarbital (PB) and dimethylsulfoxide (DMSO) have been known to maintain the functions of adult hepatocytes in vitro, they failed to induce TO expression in fetal hepatic cells. Thus far, no system has been developed that reproduces terminal differentiation of fetal hepatocytes in vitro. Here, we describe that extracellular matrices derived from Engelbreth-Holm-Swarm sarcoma (EHS) in combination with OSM or high-cell-density culture induced expression of TO as well as cytochrome P450 genes that are involved in detoxification. However, EHS alone was insufficient to induce expression of TO, although it induced TAT expression in fetal hepatocytes. In addition, high-density culture further augmented differentiation. In conclusion, the combination of signals by cytokines, cell-cell contact, and cell-matrix interaction is required for induction of adult liver functions in fetal hepatocytes in vitro. This primary culture system will be useful for studying the mechanism of liver development.
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PMID:Maturation of fetal hepatocytes in vitro by extracellular matrices and oncostatin M: induction of tryptophan oxygenase. 1202 20

Using insulin-secreting cells, we previously demonstrated that specific proteins associated with the cytosolic, secretory granule, and mitochondrial fractions undergo a novel type of phosphorylation on their histidine residues. Subsequently, we identified these proteins as the nucleoside diphosphate kinase (NDPK) [Kowluru and Metz, Biochemistry 1994;33:12495-503], the beta subunit of trimeric GTP-binding proteins [Kowluru et al., Biochem J 1996;313:97-107], and the alpha subunit of succinyl-CoA synthetase [Kowluru, Diabetologia 2001;44:89-94], respectively. Since several other enzymes of intermediary metabolism (e.g. ATP-citrate lyase and glucose-6-phosphatase) also undergo histidine phosphorylation, these initial findings may have a more generalized significance to beta cells. Herein, we characterized a novel protein histidine kinase in pancreatic beta cells, and determined it to be acid- and heat-labile as well as alkali-resistant in its phosphorylation of histone 4. Such an activity was detected in normal rat islets, human islets, and clonal beta (HIT-T15 and INS-1) cells, and could utilize either ATP or GTP as a phosphoryl donor (with K(m) values in the range of 60-100 microM). On a size-exclusion column, its molecular mass was estimated to be in the range of 60-70 kDa. It was stimulated by divalent cations (Mg(2+)>Mn(2+)>control=Ca(2+)=Zn(2+)=Co(2+)), but was resistant to polyamines. It was inactivated by known in vitro inhibitors of protein histidine phosphorylation (e.g. UDP or cromoglycate). Mastoparan, a global activator of G-proteins and insulin secretion from isolated beta cells, but not mastoparan-17, its inactive analog, stimulated histidine kinase activity and histidine phosphorylation of G(beta) subunit and insulin secretion from isolated rat islets. These studies identify, for the first time, a protein kinase activity in the pancreatic beta cell that does not act on traditional -Ser, -Tyr, or -Thr residues. They also establish a possible link between histidine kinase activity and G(beta) phosphorylation in isolated beta cells.
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PMID:Identification and characterization of a novel protein histidine kinase in the islet beta cell: evidence for its regulation by mastoparan, an activator of G-proteins and insulin secretion. 1211 Mar 68

Long-term caloric restriction (CR) has been shown to extend maximum life span in laboratory rodents. We investigated the activities of gluconeogenic and transaminase enzymes in the livers of old and young mice fed either control or calorie-restricted diets. Livers were sampled 48 h after the last scheduled feeding time. Old mice on CR showed significant increases in the activities of pyruvate carboxylase, phosphoenolpyruvate carboxykinase, fructose-1,6-bisphosphatase and glucose-6-phosphatase when compared with controls, indicating increased gluconeogenesis. Increased activities of tyrosine, tryptophan, histidine, phenylalanine, alanine and aspartate transaminases, as well as of malate and glutamate dehydrogenases were also observed, while branched-chain amino acid transaminase was unchanged. Young mice on CR showed a significant increase only in the phosphoenolpyruvate carboxykinase activity in the gluconeogenic pathway, while transaminases were increased significantly, except for tryptophan and branched-chain amino acid transaminases. Glutamate dehydrogenase also showed increased activity but malate dehydrogenase was unchanged. Increases in the level of acetyl-CoA and [Acetyl-CoA]/[CoA] ratio were observed only in the old CR mice. Our results demonstrate increased gluconeogenic activity in CR mice and are consistent with a state of increased hepatic gluconeogenesis and protein turnover during CR.
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PMID:Caloric restriction increases gluconeogenic and transaminase enzyme activities in mouse liver. 1258 90

The dual specificity tyrosine phosphorylated and regulated kinase (DYRK) family of protein kinases is a group of evolutionarily conserved protein kinases that have been characterized as regulators of growth and development in mammals, Drosophila and lower eukaryotes. In the present study, we have characterized three splicing variants of DYRK1B (DYRK1B-p65, DYRK1B-p69 and DYRK1B-p75) with different expression patterns and enzymic activities. DYRK1B-p65 and DYRK1B-p69 exhibited similar, but not identical, patterns of expression in mouse tissues, with the highest protein levels found in the spleen, lung, brain, bladder, stomach and testis. In contrast, DYRK1B-p75 was detected specifically in skeletal muscles, in the neuronal cell line GT1-7 and also in differentiated, adipocyte-like 3T3-L1 cells, but not in undifferentiated 3T3-L1 preadipocytes. A comparison of the mouse and human Dyrk1b genomic and cDNA sequences defined the alternative splicing events that produce the variants of DYRK1B. In DYRK1B-p75, transcription starts with exon 1B instead of exon 1A, generating a new translation start, which extends the open reading frame by 60 codons. This gene structure suggests that alternative promoters direct the expression of DYRK1B-p69 and DYRK1B-p75. Both splicing variants exhibited kinase activity in vitro and contained phosphotyrosine when expressed in COS-7 cells. Owing to differential recognition of the 3'-splice site in exon 9, DYRK1B-p65 differs from DYRK1B-p69 by the absence of 40 amino acids within the catalytic domain. DYRK1B-p65 lacked kinase activity in vitro and did not contain phosphotyrosine. DYRK1B-p69 and DYRK1B-p75 stimulated reporter gene activity driven by the f or kh ead in r habdosarcoma (FKHR)-dependent glucose-6-phosphatase promoter more strongly when compared with DYRK1B-p65, indicating that the DYRK1B splicing variants exhibit functional differences.
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PMID:Alternative splicing variants of dual specificity tyrosine phosphorylated and regulated kinase 1B exhibit distinct patterns of expression and functional properties. 1263 99

We have shown that physical exercise enhances insulin sensitivity of skeletal muscle in diabetes-prone Psammomys-obesus. In this study, we examined the effect of physical exercise on the liver of these animals. Three groups of animals were exposed to a 4-week protocol; high-energy diet (CH), high-energy diet and exercising (EH), and low-energy diet (CL). Different groups were studied either in a fed state or after an overnight fast, 30 minutes after intraperitoneal (IP) injection of 1 U insulin. Hepatic phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) activity was measured. Insulin signaling response was examined after insulin injection in the fast state by analyzing tyrosine phosphorylation of insulin receptor (IR) and the association between insulin receptor substrate-1 (IRS-1) and IRS-2 with phosphatidylinositol 3 kinase (PI3-K). After 4 weeks, none of the EH animals became diabetic, whereas all the CH animals became diabetic. PEPCK activity in the fed state was higher in the CH group compared with the CL and EH groups (480 +/- 28 nmol/min/mg protein, 280 +/- 30 nmol/min/mg protein, and 208 +/- 13 nmol/min/mg protein, respectively) (P < .02). G6Pase activity was higher in the CH and EH groups compared with the CL group (261 +/- 54 nmol/min/mg protein, 251 +/- 34 nmol/min/mg protein, and 75 +/- 32 nmol/min/mg protein, respectively) (P < .01). After insulin administration in the fast state, tyrosine phosphorylation of IR and association of IRS-2 with PI3-K were higher in the EH and CL groups than in the CH group. We conclude that exercise improves in vivo hepatic insulin sensitivity in diabetes-prone Psammomys-obesus.
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PMID:Physical exercise enhances hepatic insulin signaling and inhibits phosphoenolpyruvate carboxykinase activity in diabetes-prone Psammomys obesus. 1525 73


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