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

---

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

Microsomal glucokinase is solubilized by incubation in the presence of several metabolites. After solubilization of the enzymes, the membranes present free sites for specific binding of glucokinase, therefore, they can be purified by affinity chromatography on Sepharose--ATP-glucokinase. This method yields membranous vesicles which contain, in addition to glucokinase, uridylyl-transferase, phosphoglucomutase, sialyl-transferase and adenylate cyclase. Galactosyl-transferase, glucose-6-phosphatase and NADPH cytochrome c reductase are absent. It appears that functionally related enzyme from UDP-glucose biosynthesis are aggregated onto specific patches of the membrane, most likely from Golgi apparatus.
...
PMID:[Isolation by affinity chromatography of specialized membrane fractions from cat liver microsomes]. 21 51

1. Glucokinase was absent from chicken liver and only the low Km hexokinases, inhibited by AMP, ADP but not ATP, were present. 2. The Km of chicken liver glucose-6-phosphatase for glucose-6-phosphate was reduced from 5.65 to 3.75 mM following starvation, and the enzyme was inhibited by glucose. 3. Starvation of chickens for 24 hr slightly lowered the hexokinase activity and doubled glucose-6-phosphatase activity; it did not change subcellular distribution of the enzymes. Oral glucose rapidly restored the activities to fed values. 4. It was concluded that glucose uptake into, and efflux from, chicken hepatocytes, was regulated by the activity and kinetic characteristics of glucose-6-phosphatase and by the glucose-6-phosphate concentration, and that the hexokinases had little regulatory function.
...
PMID:Glucose phosphorylation and dephosphorylation in chicken liver. 23 87

The presence of carbamyl-phosphate:glucose phosphotransferase in liver nuclei of five species of mammals and birds is demonstrated. The activity is confined to nuclear membranes and is due exclusively to multifunctional glucose-6-phosphatase-phosphotransferase (D-glucose-6-phosphate phosphohydrolase; EC 3.1.3.9). The nuclear enzyme constitutes approximately 16 to 19 percent of total hepatic glucose-6-phosphatase-phosphotransferase. Carbamyl-phosphate:glucose phosphotransferase and glucose-6-P phosphohydrolase activities of membrane of chicken liver nuclei are shown to be catalytically identical with the maximally activated microsomal enzyme. A correspondence is seen in two-substrate kinetic double reciprocal plots, K-m or apparent K-m values for the various substrates, K-i values for the competitive inhibitors P-i and ATP, and pH-activity profiles. Comparative studies were carried out with various intact, disrupted, and detergent-dispersed membranous preparations by a combination of enzyme kinetic and electron microscopic techniques. It is concluded that (a) intimate interrelationships exists between catalytic behavior of this enzyme and morphological integrity of membranes of which the enzyme is a part; (b) activities of the enzyme of nuclear membrane appear quite available for physiological phosphorylative functions; and (c) interrelationships between membrane morphology and catalytic behavior of this membrane-bound enzyme may well be involved in the bioregulation of this complex, multifunctional enzyme system.
...
PMID:Carbamyl phosphate: glucose phosphotransferase and glucose-6-phosphate phosphohydrolase of nuclear membrane. Interrelationships between membrane integrity, enzymic latency, and catalytic behavior. 23 53

The subcellular localization of guanylate cyclase was examined in rat liver. About 80% of the enzyme activity of homogenates was found in the soluble fraction. Particulate guanylate cyclase was localized in plasma membranes and microsomes. Crude nuclear and microsomal fractions were applied to discontinuous sucrose gradients, and the resulting fractions were examined for guanylate cyclase, various enzyme markers of cell components, and electron microscopy. Purified plasma membrane fractions obtained from either preparation had the highest specific activity of guanylate cyclase, 30 to 80 pmol/min/mg of protein, and the recovery and relative specific activity of guanylate cyclase paralleled that of 5'-nucleotidase and adenylate cyclase in these fractions. Significant amounts of guanylate cyclase, adenylate cyclase, 5'-nucleotidase, and glucose-6-phosphatase were recovered in purified preparation of microsomes. We cannot exclude the presence of guanylate cyclase in other cell components such as Golgi. The electron microscopic studies of fractions supported the biochemical studies with enzyme markers. Soluble guanylate cyclase had typical Michaelis-Menten kinetics with respect to GTP and had an apparent Km for GTP of 35 muM. Ca-2+ stimulated the soluble activity in the presence of low concentrations of Mn-2+. The properties of guanylate cyclase in plasma membranes and microsomes were similar except that Ca-2+ inhibited the activity associated with plasma membranes and had no effect on that of microsomes. Both particulate enzymes were allosteric in nature; double reciprocal plots of velocity versus GTP were not linear, and Hill coefficients for preparations of plasma membranes and microsomes were calculated to be 1.60 and 1.58, respectively. The soluble and particulate enzymes were inhibited by ATP, and inhibition of the soluble enzyme was slightly greater. While Mg-2+ was less effective than Mn-2+ as a sole cation, all enzyme fractions were markedly stimulated with Mg-2+ in the presence of a low concentration of Mn-2+. Triton X-100 increased the activity of particulate fractions about 3- to 10-fold and increased the soluble activity 50 to 100%.
...
PMID:Localization of particulate guanylate cyclase in plasma membranes and microsomes of rat liver. 23 12

Other investigators have shown that fructose infusion in normal man and rats acutely depletes hepatic ATP and P(i) and increases the rate of uric acid formation by the degradation of preformed nucleotides. We postulated that a similar mechanism of ATP depletion might be present in patients with glucose-6-phosphatase deficiency (GSD-I) as a result of ATP consumption during glycogenolysis and resulting excess glycolysis. The postulate was tested by measurement of: (a) hepatic content of ATP, glycogen, phosphorylated sugars, and phosphorylase activities before and after increasing glycolysis by glucagon infusion and (b) plasma urate levels and urate excretion before and after therapy designed to maintain blood glucose levels above 70 mg/dl and thus prevent excess glycogenolysis and glycolysis. Glucagon infusion in seven patients with GSD-I caused a decrease in hepatic ATP from 2.25 +/- 0.09 to 0.73 +/- 0.06 mumol/g liver (P <0.01), within 5 min, persisting in one patient to 20 min (1.3 mumol/g). Three patients with GSD other than GSD-I (controls), and 10 normal rats, showed no change in ATP levels after glucagon infusion. Glucagon caused an increase in hepatic phosphorylase activity from 163 +/- 21 to 311 +/- 17 mumol/min per g protein (P <0.01), and a decrease in glycogen content from 8.96 +/- 0.51 to 6.68 +/- 0.38% weight (P <0.01). Hepatic content of phosphorylated hexoses measured in two patients, showed the following mean increases in response to glucagon; glucose-6-phosphate (from 0.25 to 0.98 mumol/g liver), fructose-6-phosphate (from 0.17 to 0.45 mumol/g liver), and fructose-1,6-diphosphate (from 0.09 to 1.28 mumol/g) within 5 min. These changes, except for glucose-6-phosphate, returned toward preinfusion levels within 20 min. Treatment consisted of continuous intragastric feedings of a high glucose dietary mixture. Such treatment increased blood glucose from a mean level of 62 (range 28-96) to 86 (range 71-143) mg/dl (P <0.02), decreased plasma glucagon from a mean of 190 (range 171-208) to 56 (range 30-70) pg/ml (P <0.01), but caused no significant change in insulin levels. Urate output measured in three patients showed an initial increase, coinciding with a decrease in plasma lactate and triglyceride levels, then decreased to normal within 3 days after treatment. Normalization of urate excretion was associated with normalization of serum uric acid. We suggest that the maintenance of blood glucose levels above 70 mg/dl is effective in reducing serum urate levels and that transient and recurrent depletion of hepatic ATP due to glycogenolysis is contributory in the genesis of hyperuricemia in untreated patients with GSD-I.
...
PMID:ATP depletion, a possible role in the pathogenesis of hyperuricemia in glycogen storage disease type I. 27 29

Human blood platelets are capable of removing Ca2+ from the cytoplasm by means of an active, ATP-dependent and cyclic AMP-stimulated transport system. Calcium-accumulating vesicles are obtained by sonicating platelets. On density gradient centrifugation, this activity is found in the heavier of two membrane fractions. Concentrated in this fraction are also the Ca2+-stimulated Mg2+-ATPase and glucose-6-phosphatase, believed to be a marker for internal membrane systems. When the isolated vesicles are loaded with Ca2+, a third band separates from the two vesicular fractions in the density gradient. This band C contains virtually all the Ca2+-accumulating activity. Evidence that this activity is due to an active uptake and not to surface binding or adsorption is presented. Whereas electron microscopy does not reveal striking differences between active and inactive fractions, differences in protein composition are revealed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. Furthermore, this band contains an enzyme system which converts arachidonic acid to malondialdehyde and therefore this fraction must be the site of prostaglandin synthesis. Membranes prepared by loading platelets with glycerol, followed by osmotic lysis are unable to accumulate calcium. In sodium dodecyl sulphate-polyacrylamide gel electrophoresis such membranes show significant differences in their protein pattern as compared to the actively Ca2+-accumulating vesicular membranes of band C. All preparations with Ca2+-accumulating activity also contain markers for plasma membranes and the question whether this activity is due exclusively to an intracellular structural element equivalent to the sarcoplasmic reticulum of muscle or whether an "extrusion pump" expelling Ca2+ to the outside of the cell is also involved, cannot yet be ;nswered.
...
PMID:Further characterization of calcium-accumulating vesicles from human blood platelets. 69 5

Human blood platelets contain no detectable activity of the enzymes fructose diphosphatase (EC 3.1.3.11), phospho-enolpyruvate carboxykinase (EC 4.1.1.32) and pyruvate carboxylase (EC 6.4.1.1.). Glucose-6-phosphatase (EC 3.1.3.9) activity is very low. Phosphofructokinase present in human blood platelets, catalyzes a reaction which can be stimulated by AMP in a platelet homogenate, due to the presence of endogenous ADP and myokinase. These enzymes are responsible for the formation of fructose-6-phosphate from fructose-1, 6-diphosphate. Pyruvate kinase (EC 2.7.1.40) in human blood platelets belongs to the M-type, which is not inhibited by ATP, at least not under the conditions applied. The results obtained indicate that gluconeogenesis in human blood platelets is not present in the way which has been established for liver and kidney.
...
PMID:Insignificance of gluconeogenesis in human blood platelets. 112 26

Ciprofibrate, a peroxisome proliferating agent, induces cell proliferation in rodent liver during the early periods of exposure. Since Ca2+ plays an important role in mitogenesis, we have investigated the effects of ciprofibrate on hepatic endoplasmic reticulum (ER) Ca(2+)-ATPase, which in part regulates Ca2+ homeostasis. A single oral dose of 200 mg/kg ciprofibrate to male F344 rats produced a transient decrease in liver microsomal Ca(2+)-ATPase activity to 48% of control levels at 24 hr post-exposure. Activity had returned to control levels by 48 and 72 hr after exposure. The decrease in Ca(2+)-ATPase activity was not a function of non-specific enzymatic inhibition, since activity of another microsomal enzyme, glucose-6-phosphatase, was not altered in ciprofibrate-exposed rats. Using an ATP-driven 45Ca2+ accumulation assay, rats exposed to 25, 100 and 200 mg/kg ciprofibrate exhibited a dose-dependent inhibition of liver microsomal Ca2+ accumulation at 24 hr post-exposure. Analysis of Western immunoblots using a polyclonal antibody to the liver ER Ca(2+)-ATPase revealed a marginal increase in Ca(2+)-ATPase protein content in microsomes prepared from ciprofibrate-exposed rats compared to controls 24 hr post-exposure. These data indicate that the reduction of Ca(2+)-ATPase activity is not attributable to diminished Ca(2+)-ATPase protein content in vivo and, therefore, is due to a functional inhibition of the enzyme. Ciprofibrate also produced a concentration-dependent inhibition of rat liver ER Ca(2+)-ATPase activity in vitro (IC50 approximately 170 microM). In freshly isolated rat hepatocytes, ciprofibrate elevated the free intracellular calcium concentration ([Ca2+]i) in the presence and absence of extracellular calcium. Collectively, these results suggest that ciprofibrate mobilizes hepatic [Ca2+]i via inhibition of the ER Ca(2+)-ATPase. These events may lead to an environment of elevated [Ca2+]i during the early stages of ciprofibrate exposure and may serve to augment Ca(2+)-dependent processes, thus playing a pivotal role in the acute mitogenic response.
...
PMID:Reduction of rat liver endoplasmic reticulum Ca(2+)-ATPase activity and mobilization of hepatic intracellular calcium by ciprofibrate, a peroxisome proliferator. 153 54

Several pharmaceutical agents, manufacturing chemicals, and environmental contaminants were found to act primarily as promoting agents in an initiation-promotion paradigm. The phenotypic distribution of four enzyme markers--placental glutathione-S-transferase (PGST), gamma-glutamyl transpeptidase (GGT), canalicular ATPase (ATPase), and glucose-6-phosphatase (G6Pase)--was analyzed in altered hepatic foci (AHF) by quantitative stereology. The number and volume distribution of AHF were determined for each promoter tested. For phenobarbital and 2,3,7,8-tetrachloro-p-dioxin, PGST and GGT together scored 100% of the AHF; for 1-(phenylazo)-2-naphthol (CI solvent yellow 14) and chlorendic acid, PGST alone marked 90% of the AHF; after chronic administration of WY-14,643, ATP and G6Pase were the predominant markers. In rats fed tamoxifen, G6P scored more than half of the AHF. Differences in the number of AHF promoted by each of these agents and in their phenotypic distributions may reflect the differentially responsive nature of individual initiated hepatocytes to the action of specific promoters. Since the chronic bioassay of suspected carcinogens does not allow one to differentiate between weak complete carcinogens and those carcinogenic agents that act in a reversible manner to promote the growth of previously initiated cells, the partial hepatectomy, altered-hepatic-focus model of cancer development is proposed as a supplement to the chronic bioassay for the identification of those carcinogenic agents that are primarily, if not exclusively, promoting agents in rat liver.
...
PMID:An initiation-promotion assay in rat liver as a potential complement to the 2-year carcinogenesis bioassay. 185 24

Dehydroepiandrosterone (DHEA) treatment is effective in preventing or delaying the onset of various genetic and induced disorders of mice and rats. Associated with the beneficial therapeutic effects exerted by action of this steroid is the development of hepatomegaly. To determine whether the changes associated with hepatomegaly also involve alterations in activities of tissue enzymes, we evaluated the effects of DHEA (0.45% in food, w/w) on hepatic protein kinases, phosphatases, and lipogenic enzymes in mice of various strains. The rates of fatty acid and cholesterol syntheses also were evaluated. DHEA administration resulted in profound changes in the sodium dodecylsulfate-polyacrylamide gel electrophoresis patterns of endogenous radiophosphorylated proteins obtained by incubation of liver homogenates with (gamma-32P]ATP. These changes were dependent upon the medium used for homogenization. Thus, when homogenates of liver tissue of DHEA-treated mice were prepared in Tris buffer containing sucrose (0.25 M) there was a marked decrease in phosphorylation of the proteins of relative molecular weight approximately 116,000 (Mr approximately 116,000), approximately 82,000, approximately 80,000, approximately 58,000, approximately 56,000, approximately 48,000, approximately 34,000, and approximately 31,000 compared with controls. With liver homogenates of DHEA-treated mice prepared in Tris buffer alone, there was a marked increase in phosphorylation of the proteins of Mr approximately 70,000, approximately 49,000, approximately 34,000, approximately 31,000, and 28,000 compared with controls. Moreover, the specific activity of kinases for endogenous protein acceptors in liver of control mice was higher than that in liver of DHEA-treated animals. The specific activities of casein kinase, cAMP-dependent protein kinase, and cGMP-dependent protein kinase remained unchanged with DHEA treatment, but the specific activity of histone kinase was increased approximately 30%. Long-term administration of DHEA also was associated with increases in the specific activities of liver AMPase and GTPase (approximately two times), but not of other nucleotidases, alkaline phosphatase, acid phosphatase, glucose-6-phosphatase, or phosphotyrosine phosphatase. The activity of hepatic NADP-linked malic enzyme was increased significantly (two to three times) by DHEA treatment of female mice of three different strains, but was unchanged in male C57BL/6 mice. The specific activities of hepatic glucose-6-phosphate dehydrogenase, NADP-linked isocitrate dehydrogenase, and ATP-citrate lyase were not affected significantly by DHEA treatment of mice. The rate of hepatic lipogenesis, determined by incorporation of tritium from 3H2O into fatty acids, was decreased approximately 70% in DHEA-treated mice, while the rate of cholesterol synthesis was increased approximately 44% compared with controls.
...
PMID:Dehydroepiandrosterone feeding and protein phosphorylation, phosphatases, and lipogenic enzymes in mouse liver. 215 82


<< Previous 1 2 3 4 5 6 7 8 9 Next >>

---