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)

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.
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PMID:[Isolation by affinity chromatography of specialized membrane fractions from cat liver microsomes]. 21 51

A Golgi-rich fraction is prepared from cat hepatocytes by the means of a four-step sucrose density gradient. The material applied to this gradient is composed either of smooth microsomes prepared from healthy animals, or of total microsomes prepared from cat treated by 50 per cent ethanol (0.6 g/100 g body weight, administered by stomach tube). A light fraction (d : 1.10) is obtained by the two procedures. It does not show any glucose-6-phosphatase activity, but is enriched in sialyltransferase, known as a marker enzyme for Golgi apparatus. It also contains the three enzymes implicated in the biosynthetic pathway for UDP-glucose (glucokinase, phosphoglucomutase and UTP : glucose-1-phosphate uridylyltransferase). UDP-glucose being the ultimate substrate in membranous glucosylation reactions, these results could support the hypothesis that sugar-nucleotides necessary for the glycoprotein biosynthesis are produced in the Golgi vesicles directly.
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PMID:[Presence of enzymes catalyzing UDP-glucose biosynthesis in a low density Golgi fractions of cat hepatocytes]. 22 65

To determine the hepatic and intestinal toxicity of sodium cyanate, this compound was administered to rats by orogastric tube (PO) or intraperitoneal injection (IP). At low dosage (50 mg. per kilogram per day PO for 8 weeks), the animals showed no clinical effects other than mild lethargy. They had normal intestinal absorption studies, but demonstrated decreased liver G6PD activity and a slight increase in hepatic glycogen. At higher dose levels (200 mg. per kilogram per day PO for 10 days, 400 mg. per kilogram per day PO for 3 days, and 100 mg. per kilogram per day IP for 10 days), the animals became very lethargic and developed hind-limb paralysis; many animals died during the period of dosing. The severity and rate of onset of symptoms increased proportionally with the dose level. Liver sections from rats receiving these higher doses showed striking increases in glycogen deposition. Activities of hepatic enzymes involved in glycogen synthesis and degradation were measured in rats receiving 200 mg. per kilogram per day PO or 100 mg. per kilogram per day IP. Significant decreases were noted in the activities of glucose-6-phosphatase and G6PD in PO-dosed rats. The activities of phosphorylase, UDPG-pyrophosphorylase, glycogen synthetase, phosphoglucomutase, and debrancher did not differ from control rats. In IP-dosed rats, significant decreases were observed in the activities of glucose-6-phosphatase, G6PD, phosphorylase, and UDPG-pyrophosphorylase, but not in the other glycogen-related enzymes. Our data suggest that sodium cyanate affects several enzymes of hepatic glycogen metabolism but that the enzymes vary in their susceptibility (glucose-6-phosphatase and G6PD greater than phosphorylase and UDPG pyrophosphorylase.
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PMID:In vivo hepatic and intestinal toxicity of sodium cyanate in rats: cyanate-induced alterations in hepatic glycogen metabolism. 23 70

We examined the intracellular site(s) and topology of glucosylceramide (GlcCer) synthesis in subcellular fractions from rat liver, using radioactive and fluorescent ceramide analogues as precursors, and compared these results with those obtained in our recent study of sphingomyelin (SM) synthesis in rat liver [Futerman, Stieger, Hubbard & Pagano (1990) J. Biol. Chem. 265, 8650-8657]. In contrast with SM synthesis, which occurs principally at the cis/medial Golgi apparatus, GlcCer synthesis was more widely distributed, with substantial amounts of synthesis detected in a heavy (cis/medial) Golgi-apparatus subfraction, a light smooth-vesicle fraction that is almost devoid of an endoplasmic-reticulum marker enzyme (glucose-6-phosphatase), and a heavy vesicle fraction. Furthermore, no GlcCer synthesis was detected in an enriched plasma-membrane fraction after accounting for contamination by Golgi-apparatus membranes. These results suggest that a significant amount of GlcCer may be synthesized in a pre- or early Golgi-apparatus compartment. Unlike SM synthesis, which occurs at the luminal surface of the Golgi apparatus, GlcCer synthesis appeared to occur at the cytosolic surface of intracellular membranes, since (i) limited proteolytic digestion of intact Golgi-apparatus vesicles almost completely inhibited GlcCer synthesis, and (ii) the extent of UDP-glucose translocation into the Golgi apparatus was insufficient to account for the amount of GlcCer synthesis measured. These findings imply that, after its synthesis, GlcCer must undergo transbilayer movement to the luminal surface to account for the known topology of higher-order glycosphingolipids within the Golgi apparatus and plasma membrane.
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PMID:Determination of the intracellular sites and topology of glucosylceramide synthesis in rat liver. 174 3

Synergism of glucose and fructose in net glycogen synthesis was studied in perfused livers from 24-h fasted rats. With either glucose or fructose alone, net glycogen deposition did not occur (p greater than 0.10 for each), whereas the addition of both together resulted in significant glycogen accumulation (net glycogen accumulation was 0.21 +/- 0.03 mumol of glucose/g of liver/min at 2 mM fructose and 30 mM glucose, p less than 0.001). To better understand this synergism, intermediary substrate levels were compared at steady state with various glucose levels in the absence and in the presence of 2 mM fructose. Independent of fructose, hepatic glucose and glucose 6-phosphate increased proportionally when glucose level in the medium was raised (r = 0.86, p less than 0.001). Unlike glucose 6-phosphate, UDP-glucose did not consistently increase with glucose (p greater than 0.10); in fact, there was a small decrease at a very high glucose level (30 mM), a result consistent with the well-established activation of glycogen synthase by glucose. With elevated glucose, the level of glucose 6-phosphate was strongly correlated with glycogen content (r = 0.71, p less than 0.01, slope = 32). Adding fructose increased the "efficiency" of glucose 6-phosphate to glycogen conversion: the effect of a given increment in glucose 6-phosphate upon glycogen accumulation was increased 2.6-fold (r = 0.73, p less than 0.01, slope = 86). A kinetic modeling approach was used to investigate the mechanisms by which fructose synergized glycogen accumulation when glucose was elevated. Based on steady-state hepatic substrate levels, net hepatic glucose output, and net glycogen synthesis rate, the model estimated the rate constants of major enzymes and individual fluxes in the glycogen metabolic pathway. Modeling analysis is consistent with the following scenario: glycogen synthase is activated by glucose, whereas glucose-6-phosphatase was inhibited. In addition, the model supports the hypothesis that fructose synergizes net glycogen accumulation due to suppression of phosphorylase. Overall, our analysis suggests that glucose enhances the metabolic flux to glycogen by inducing a build up of glucose 6-phosphate via combined effects of mass action and glucose-6-phosphatase inhibition and activating glycogen synthase and that fructose enhances glycogen accumulation by retaining glycogen via phosphorylase inhibition.
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PMID:Synergism of glucose and fructose in net glycogen synthesis in perfused rat livers. 302 36

Severe hepatic damage with submassive necrosis induced in rats by an intraperitoneal injection of a single dose of galactosamine hydrochloride was studied. In the severely damaged liver, the remarkable decreases of glycogen and UDPG in the damaged liver were seen. This means extreme decrease in the reserve power of glycolysis. Moreover, the activities of glucose-6-phosphatase and fructose-1,6-diphosphatase decreased. Therefore, the glucose release from liver into the blood stream decreases and the inhibition of gluconeogenesis occurs. In the damaged liver, the decrease of UTP which is essential for the synthesis of sugar moiety of polysaccharide, was seen. Further, the activities of L-glutamine: D-fructose-6-phosphate amidotransferase and UDP N-acetylglucosamine 2'-epimerase which are two key enzymes of polysaccharide synthesizing enzyme were seen to decrease remarkably. In the damaged liver, the glycoprotein fraction decreased more strikingly than the acid mucopolysaccharide fraction. Moreover, the decrease of fructose-1,6-diphosphatase activity seems also to effect on the inhibition of polysaccharide synthesis. In these respects, in the severe hepatic damage, the synthesis of glycoprotein which is essential for liver cell seems to be inhibited.
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PMID:Studies on severe hepatic damage induced by galactosamine. 617 14

The mechanism by which exogenous glucose stimulates the incorporation of hepatic glucose-6-phosphate into glycogen in fasted rats has not been clearly delineated. We gave glucose intragastrically over a 3.5-h period during which liver glycogen was deposited at linear rates. Simultaneous primed continuous infusion of [2-3H] or [3-3H]glucose established that under these conditions absolute carbon flow through hepatic glucose-6-phosphatase was greatly suppressed. After 1 h, hepatic [UDP-glucose] and [glucose-6-phosphate] had fallen by 50-60% and the former remained low throughout the experiment. By contrast, [glucose-6-phosphate] rebounded to its initial value by 2 h and remained at this level during the subsequent hour. We interpret the data as follows. Exogenous glucose, in addition to acting as a precursor of liver glucose-6-phosphate, causes diversion of the latter away from free glucose formation and into glycogen synthesis. The fall in [UDP-glucose] is in accord with a glucose-induced activation of glycogen synthase, as proposed by Hers (Annu. Rev. Biochem. 1976; 45:167-89.). However, the fall-rise sequence of glucose-6-phosphate concentration constitutes the first direct evidence in vivo for simultaneous inhibition at the level of glucose-6-phosphatase.
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PMID:Evidence for suppression of hepatic glucose-6-phosphatase with carbohydrate feeding. 631 14

To examine the relationship between the plasma glucose concentration (PG) and the pathways of hepatic glucose production (HGP), five groups of conscious rats were studied after a 6-h fast: (a) control rats (PG = 8.0 +/- 0.2 mM); (b) control rats (PG = 7.9 +/- 0.2 mM) with somatostatin and insulin replaced at the basal level; (c) control rats (PG = 18.1 +/- 0.2 mM) with somatostatin, insulin replaced at the basal level, and glucose infused to acutely raise plasma glucose by 10 mM; (d) control rats (PG = 18.0 +/- 0.2 mM) with somatostatin and glucose infusions to acutely reproduce the metabolic conditions of diabetic rats, i.e., hyperglycemia and moderate hypoinsulinemia; (e) diabetic rats (PG = 18.4 +/- 2.3 mM). All rats received an infusion of [3-3H]glucose and [U-14C]lactate. The ratio between hepatic [14C]UDP-glucose sp act (SA) and 2X [14C]-phosphoenolpyruvate (PEP) SA (the former reflecting glucose-6-phosphate SA) measured the portion of total glucose output derived from PEP-gluconeogenesis. In control rats, HGP was decreased by 58% in hyperglycemic compared to euglycemic conditions (4.5 +/- 0.3 vs. 10.6 +/- 0.2 mg/kg.min; P < 0.01). When evaluated under identical glycemic conditions, HGP was significantly increased in diabetic rats (18.9 +/- 1.4 vs. 6.2 +/- 0.4 mg/kg.min; P < 0.01). In control rats, hyperglycemia increased glucose cycling (by 2.5-fold) and the contribution of gluconeogenesis to HGP (91% vs. 45%), while decreasing that of glycogenolysis (9% vs. 55%). Under identical plasma glucose and insulin concentrations, glucose cycling in diabetic rats was decreased (by 21%) and the percent contribution of gluconeogenesis to HGP (73%) was similar to that of controls (84%). These data indicate that: (a) hyperglycemia causes a marked inhibition of HGP mainly through the suppression of glycogenolysis and the increase in glucokinase flux, with no apparent changes in the fluxes through gluconeogenesis and glucose-6-phosphatase; under similar hyperglycemic hypoinsulinemic conditions: (b) HGP is markedly increased in diabetic rats; however, (c) the contribution of glycogenolysis and gluconeogenesis to HGP is similar to control animals.
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PMID:Mechanism by which hyperglycemia inhibits hepatic glucose production in conscious rats. Implications for the pathophysiology of fasting hyperglycemia in diabetes. 839 19

The net release of glucose from the liver, or hepatic glucose production (HGP), and apparent gluconeogenesis (GNG) are reduced by exogenous glucose. We investigated the changes in metabolic fluxes responsible. Flux through the hepatic GNG pathway was quantified by mass isotopomer distribution analysis (MIDA) from [2-13C]glycerol. Unidirectional flux across hepatic glucose-6-phosphatase (G-6-Pase), or total hepatic glucose output (THGO), and hepatic glucose cycling (HGC) were also measured by using glucuronate (GlcUA) to correct for glucose 6-phosphate (G-6-P) labeling. Infusion of glucose (15-30 mg.kg-1.min-1 iv) to 24 h-fasted rats caused two important metabolic alterations. First was a significant increase in hepatic glucose uptake and HGC: > 60% of THGO was from HGC. Second, although flux through hepatic G-6-P increased (from 15.7 to 17.7-22.7 mg.kg-1.min-1), the partitioning of G-6-P flux changed markedly [from 30-35% to 55-60% entering UDP-glucose (UDP-Glc), P < 0.01]. Total flux through the GNG pathway remained active during intravenous glucose, but increased partitioning into UDP-Glc lowered GNG flux plasma glucose by 50%. In summary, the suppression of HGP and GNG flux into glucose is not primarily due to reduced carbon flow through hepatic G-6-Pase or the hepatic GNG pathway. THGO persists, but hepatic G-6-P is derived increasingly from plasma glucose, and flow through GNG persists, but the partitioning coefficient of G-6-P into UDP-Glc doubles. These adjustments permit net HGP to fall despite increased total production of hepatic G-6-P during administration of glucose.
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PMID:Altered fluxes responsible for reduced hepatic glucose production and gluconeogenesis by exogenous glucose in rats. 903 66

Measurement of hepatic glucose production (HGP) by standard isotope dilution reveals only the net release of glucose from the liver, not the flux across glucose-6-phosphatase ([G6Pase] or total hepatic glucose output), hepatic glucose cycling (HGC), irreversible glucose disposal into glycogen in the liver (hepatic Rd), or net hepatic glucose balance. We describe two independent isotopic techniques for measuring these parameters in vivo, both of which use secreted glucuronate (GlcUA). HGC can be quantified by measuring a correction factor for glucose label retained in hepatic glucose-6-phosphate (G6P), sampled as GlcUA. A complementary technique for measuring total hepatic glucose output is also described (reverse dilution), requiring administration of no labeled glucose but instead a labeled gluconeogenic precursor and unlabeled glucose. Hepatic Rd is calculated by multiplying the rate of appearance (Ra) of hepatic UDP-glucose ([UDP-glc] based on dilution of labeled galactose in GlcUA) times the direct entry of glucose into hepatic UDP-glc and the fraction of labeled UDP-glc retained in the liver. The sum of hepatic Rd plus HGC represents the total hepatic glucose phosphorylation rate. Rats received intravenous (i.v.) glucose infusions at a rate of 15 to 30 mg/kg/min after a 24-hour fast. Despite a suppression of net HGP more than 50%, total hepatic glucose output was not significantly decreased, because of increased HGC. Total hepatic glucose output calculated by reverse dilution yielded similar results during i.v. glucose infusions at 15 mg/kg/min, although values were higher than obtained by the correction-factor method at 30 mg/kg/min. The fraction of labeled UDP-glc released into blood glucose, representing a hepatic glycogen cycle, decreased from 35% (fasted) to nearly 0% (i.v. glucose 30 mg/kg/min). Hepatic Rd was 1.4, 4.6, and 7.5 mg/kg/min (fasted and i.v. glucose 15 and 30 mg/kg/min, respectively); total hepatic glucose phosphorylation increased substantially (from 4.2 to 8.5 to 12.7 mg/kg/min) and net hepatic glucose balance changed from negative to positive during i.v. glucose. In conclusion, hepatic G6Pase flux, glucose phosphorylation, HGC, disposal of glucose into glycogen, and net glucose balance can be measured noninvasively in vivo under various metabolic conditions by techniques involving the GlcUA probe.
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PMID:Hepatic glucose-6-phosphatase flux and glucose phosphorylation, cycling, irreversible disposal, and net balance in vivo in rats. Measurement using the secreted glucuronate technique. 943 32


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