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)

The distribution of glucose-6-phosphatase (G6Pase) activity in the epithelium of the small intestine in mouse embryos (the last 4 days of gestation) was studied by electron microscope cytochemistry and by enzymatic assays. At 16 days, the lead phosphate deposited by the cytochemical reaction is localized on the rough endoplasmic reticulum (RER) and nuclear envelope of very few cells in the duodenum and jejunum. Positive cells are more frequently seen in the upper part of the developing villi. At 17 days of gestation, a tremendous burst in RER differentiation is noticed in all parts of the small intestine and concomitantly glycogen disappears. At 18 days of gestation all the principal cells of the intestinal mucosa show a well differentiated positive RER and the enzyme is also present in the smooth endoplasmic reticulum. Biochemically, G6Pase activity is detected in the proximal 2 thirds of the small intestine at 17 days of gestation and appears at 18 days in the last third. Afterwards the activity increases up until birth. These results suggest (1) that the endoplasmic reticulum differentiates very late in the intestinal mucosa of mouse embryos (2) that the differentiation with respect to G6Pase is asynchronous between the enterocytes, (3) that for a given cell all the cisternae of RER are involved in G6Pase synthesis at the same moment and (4) that the enterocytes of the duodenum differentiate sooner and faster that those of the jejunum and ileum.
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PMID:Developmental pattern of glucose-6-phosphatase activity in the small intestine of the mouse fetus. 22 20

Kinetic studies indicate that glucose-6-phosphatase is a multifunctional enzyme. a) Phosphohydrolase activities. The mannose-6-phosphatase activity is low (Km = 8 mM, VM = 90 nmoles. min-1mg-1). The enzyme shows a strong affinity for glucose-6-phosphate (Km = 2.5 mM, VM = 220 nmoles.min-1mg-1). beta-glycerophosphate (K1 = 30 mM), D-glucose (Ki = 120 mM) are mixed type inhibitors; pyrophosphate (Ki = 2 mM) is a non competitive one. b) Phosphotransferase activities. Di and triphosphate adenylic nucleosides or phosphoenol pyruvate are not substrates. Carbamylphosphate serves as a phosphoryl donor with D-glucose as acceptor. The phosphate transfer is consisstent with a random mechanism in which the binding of one substrate increases the enzymes affinity for the second substrate. Apparent Km values for carbamyl-phosphate range from 5.2 mM (D-glucose concentration leads to infinity) to 8 mM (D-glucose concentration leads to 0). The corresponding apparent Km values for D-glucose are 59 mM (carbamyl-phosphate concentration leads to infinity) to 119 mM (carbamyl-phosphate concentration leads to 0). Maximal reaction velocity with infinite levels of both substrates is 270 nmoles.min-1.mg-1. Pyrophosphate is a poor phosphoryl donnor (Km = 55 mM with D-glucose concentration 250 mM). In addition we do not find any latency; detergents, namely sodium deoxycholate, Triton X 100 do not affect or inhibit glucose-6-phosphatase activity.
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PMID:[Monkey liver microsomal glucose-6-phosphatase]. 23 60

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.
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PMID:Carbamyl phosphate: glucose phosphotransferase and glucose-6-phosphate phosphohydrolase of nuclear membrane. Interrelationships between membrane integrity, enzymic latency, and catalytic behavior. 23 53

A model for microsomal glucose 6-phosphatase (EC 3.1.3.9) is presented. Glucose 6-phosphatase is postulated to be resultant of the coupling of two components of the microsomal membrane: 1) a glucose 6-phosphate - specific transport system which functions to shuttle the sugar phosphate from the cytoplasm to the lumen of the endoplasmic reticulum; and 2) a catalytic component, glucose-6-P phosphohydrolase, bound to the luminal surface of the membrane. A large body of existing data was shown to be consistent with this hypothesis. In particular, the model reconciles well-documented differences in the kinetic properties of the enzyme of untreated and modified microsomal preparations. Characteristic responses of the enzyme to changes in nutritional and hormonal states may be attributed to adaptations which alter the relative capacities of the transport and catalytic components.
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PMID:On the involvement of a glucose 6-phosphate transport system in the function of microsomal glucose 6-phosphatase. 23 36

1) Rat liver microsomes exhibit only a weak hydrolyzing activity towards galactose 6-phosphate. Disruption of the microsomal vesicles does not change the apparent Michaelis constant for this substrate but enhances the apparent maximum velocity. 2) The inhibition of microsomal glucose-6-phosphatase (EC 3.1.3.9) by galactose 6-phosphate is of the competitive type in intact and disrupted microsomal vesicles, suggesting that both substrates are hydrolyzed by the same enzyme. 3) The high degree of latency found for the hydrolysis of galactose 6-phosphate compared to glucose 6-phosphate indicates the presence of a carrier for glucose 6-phosphate in the microsomal membrane. 4) Since glucose as a product is not trapped inside the microsomal vesicles, this sugar probably is able to penetrate the microsomal membrane.
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PMID:Membrane effects on hepatic microsomal glucose-6-phosphatase. 24 94

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.
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PMID:ATP depletion, a possible role in the pathogenesis of hyperuricemia in glycogen storage disease type I. 27 29

The effect of chronic ethanol consumption on the ability of isolated liver fractions to metabolize the carcinogen N-nitrosopyrrolidine (NPY) was examined. Microsomal fractions of treated animals exhibited increased rates of alpha-hydroxylation of NPY. Similar increases in the specific activities of aniline hydroxylase, reduced nicotinamide adenine dinucleotide phosphate cytochrome c reductase, and the specific content of cytochrome P-450 were also observed. In contrast, no differences in the specific activities of benzo(a)pyrene hydroxylase or glucose-6-phosphatase were observed. Liver postmitochondrial supernatants from ethanol-consuming animals were able to produce 5 times more mutants than did control preparations. It is concluded that alpha-hydroxylation of NPY is probably the mechanism by which NPY is converted to a mutagen and that this pathway can be induced by ethanol.
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PMID:Enhanced metabolism and mutagenesis of nitrosopyrrolidine in liver fractions isolated from chronic ethanol-consuming hamsters. 57 Aug 82

Experiments were performed to localize the hepatic microsomal enzymes of phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol biosynthesis to the cytoplasmic or lumenal surface of microsomal vesicles. Greater than 90 percent of the activities of fatty acid-CoA ligase (EC 6.2.1.3), sn-glycerol 3-phosphate acyltransferase (EC 2.3.1.15), lysophosphatidic acid acyltransferase, diacylglycerol acyltransferase (EC 2.3.1.20), diacylglycerol cholinephosphotransferase (EC 2.7.8.2), and diacylglycerol ethanolaminephosphotransferase (EC 2.7.8.1) was inactivated by proteolysis of intact microsomal vesicles. The phosphatidic acid phosphatase (EC 3.1.3.4) was not inactivated by any of the protease tested. Under conditions employed, <5 percent of the luminal mannose-6-phosphatase (EC 3.1.3.9) activity was lost. After microsomal integrity was disrupted with detergents, protease treatment resulted in a loss of >74 percent of the mannose-6-phosphatase activity. The latency of the mannose-6-phosphatase activity was not affected by protease treatment. Mannose-6-phosphatase latency was not decreased by the presence of the assay components of several of the lipid biosynthetic activities, indicating that those components did not disrupt the microsomal vesicles. None of the lipid biosynthetic activities appeared latent. The presence of a protease-sensitive component of these biosynthetic activities on the cytoplasmic surface of microsomal vesicles, and the absence of latency for any of these biosynthetic activities suggest that the biosynthesis of phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol occurs asymmetrically on the cytoplasmic surface of the endoplasmic reticulum. The location of biosynthetic activities within the transverse plane of the endoplasmic reticulum is of particular interest for enzymes whose products may be either secreted or retained within the cell. Phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol account for the vast majority of hepatic glycerolipid biosynthesis. The phospholipids are utilized for hepatic membrane biogenesis and for the formation of lipoproteins, and the triacylglycerols are incorporated into lipoproteins or accumulate within the hepatocyte in certain disease states (14). The enzymes responsible for the biosynthesis of these glycerolipids (Scheme I) from fatty acids and glycerol-3P have all been localized to the microsomal subcellular fraction (12, 16, 29, 30). Microsomes are derived from the endoplasmic reticulum and are sealed vesicles which maintain proper sidedness. (11, 22). The external surface of these vesicles corresponds to the cytoplasmic surface of the endoplasmic reticulum. Macromolecules destined for secretion must pass into the lumen of the endoplasmic reticulum (5, 23). Uncharged molecules of up to approximately 600 daltons are able to enter the lumen of rat liver microsomes, but macromolecules and charged molecules of low molecular weight do not cross the vesicle membrane (10, 11). Because proteases neither cross the microsomal membrane nor destroy the permeability barrier of the microsomal vesicles, only the enzymes and proteins located on the cytoplasmic surface of microsomal vesicles are susceptible to proteolysis unless membrane integrity is disrupted (10, 11). By use of this approach, several enzymes and proteins have been localized in the transverse plane of microsomal membranes (11). With the possible exception of cytochrome P 450, all of the enzymes and proteins investigated were localized asymmetrically by the proteolysis technique (11). By studies of this type, as well as by product localization, glucose-6-phosphate (EC 3.1.3.9) has been localized to the luminal surface of microsomal vesicles (11) and of the endoplasmic reticulum (18, 19). All microsomal vesicles contain glucose-6-phosphatase (18, 19) which can effectively utilize mannose-6-P as a substrate, provided the permeability barrier of the vesicles has been disrupted to allow the substrate access to the active site located on the lumenal surface (4). An exact correspondence between mannose- 6-phosphate activity and membrane permeability to EDTA has been established (4). The latency of mannose-6-phosphatase activity provides a quantitative index of microsomal integrity (4.) Few of the microsomal enzymes in the synthesis of phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol have been solubilized and/or purified, and little is known about the topography of these enzymes in the transverse or lateral planes of the endoplasmic reticulum. An asymmetric location of these biosynthetic enzymes on the cytoplasmic or lumenal surface of microsomal vesicles may provide a mechanism for regulation of the glycerolipids to be retained or secreted by the cell, and for the biogenesis of asymmetric phospholipid bilayers. In this paper, we report investigations on the localization of all seven microsomal enzymes (Scheme I) in the biosynthesis of triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine, using the protease technique with mannose-6-phosphatase serving as luminal control activity. The latency of these lipid biosynthetic enzymes was also investigated, using the latency of mannose-6-phosphatase as an index of microsomal integrity.
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PMID:Evidence that biosynthesis of phosphatidylethanolamine, phosphatidylcholine, and triacylglycerol occurs on the cytoplasmic side of microsomal vesicles. 61 95

Insluin injected intravenously caused a rapid, marked decrease in hepatic glucose secretion in the rabbit, as determined by an isotope-dilution procedure. This was associated with a decrease in the concentrations of gluconeogenic intermediates from phosphoenolpyruvate to triose phosphates, inclusive, compatible with inhibition of gluconeogenesis at phosphoenolpyruvate carboxykinase. The concentration of glucose 6-phosphate was unaltered but that of hepatic glucose was reduced. The specific activities of the hexose phosphates, relative to that of liver glucose, were the same in control and insulin-treated animals. These observations can be explained by a decrease in the activity of glucose-6-phosphatase. It is concluded that this enzyme is a control point for hepatic glucose production and is inhibited by insulin. In the rat, insulin produced a rapid fall in blood sugar. The hepatic glucose output remained normal despite a fall in hepatic glucose 6-phosphate concentration during the initial period of insulin action. This suggests that glucose-6-phosphate returned to normal with no change in the rate of glucose production. The data suggest that in the rat, insulin produces a transient increase in glucose-6-phosphatase activity.
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PMID:Insulin control of hepatic glucose production. 112 Feb 88

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.
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PMID:Insignificance of gluconeogenesis in human blood platelets. 112 26


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