Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.3.9 (glucose-6-phosphatase)
 3,081 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Vanadate has been found to be a potent inhibitor of both the hydrolytic and synthetic activities of the multifunctional enzyme glucose-6-phosphatase (D-glucose-6-phosphate phosphohydrolase, EC 3.1.3.9). The enzyme, when studied in both microsomal preparations and in situ using permeable isolated hepatocytes, is inhibited by micromolar concentrations of vanadate. The inhibition by vanadate is greater in detergent-treated than in untreated microsomes. In both the microsomal preparations and permeable hepatocytes, the inhibition by vanadate is competitive with the phosphate substrate and is greater for the phosphotransferase than the hydrolase activity of the enzyme. The Ki values of vanadate for carbamyl-phosphate : glucose phosphotransferase and glucose-6-phosphate phosphohydrolase determined with permeable hepatocytes are in good agreement with the values determined with detergent-dispersed microsomes. The previously described inhibition of glucose-6-phosphate phosphohydrolase by ATP (Nordlie, R.C., Hanson, T.L., Johns, P.T. and Lygre, D.G. (1968) Proc. Natl. Acad. Sci. USA 60, 590-597) can now be explained by the vanadium contamination of the commercially available ATP samples used. In contrast with glucose-6-phosphatase, hepatic glucokinase and hexokinase were not inhibited by vanadate. Physiological implications and utilitarian experimental applicability of vanadate as a selective metabolic probe, based on these observations, are suggested.
 ...
PMID:Vanadate: a potent inhibitor of multifunctional glucose-6-phosphatase. 627 21

Periportal and perivenous hepatocytes contain different activities (V) of antagonistic key enzymes such as glucokinase and glucose-6-phosphatase. In order to get an insight into the metabolism of the periportal and perivenous area the flux rates (v) of the glucose/glucose-6-phosphate cycle were calculated on the basis of the Michaelis-Menten equation using the measured zonal concentrations of glucose and glucose 6-phosphate, the zonal activities of glucokinase and glucose-6-phosphatase previously reported and the half-saturating substrate concentrations (Km) of the two enzymes found in the literature. The concentrations of glucose were obtained as a first approximation by measuring the concentrations in portal (= periportal) and hepatovenous (= perivenous) blood; those of glucose 6-phosphate were calculated from the levels determined in microdissected periportal and perivenous liver tissue. The calculations showed (a) that the overall cycling rates agreed remarkably well with those reported for intact animals and (b) that during a normal feeding rhythm the periportal zone should catalyze net glucose output and the perivenous zone should mediate net glucose uptake, as proposed by the model of 'metabolic zonation'.
 ...
PMID:The glucose/glucose-6-phosphate cycle in the periportal and perivenous zone of rat liver. 628 Oct 9

A previous report from this laboratory demonstrated age-related differences in the hormonal regulation of hepatic glucose-6-phosphatase (G-6-Pase). A detailed kinetic analysis of G-6-Pase activity has been performed to distinguish between effects on the microsomal carrier for glucose-6-phosphate and those on the enzyme itself. The maximum velocity (Vmax) was determined in untreated microsomes and microsomes treated with sodium deoxycholate (DOC); the Vmax of the enzyme (VE) was equal to the Vmax in the presence of DOC, and the Vmax of the carrier (VT) was calculated from the Vmax of untreated microsomes and the latency (the activity of DOC-treated microsomes not expressed by the intact preparation). The age-related decrease in G-6-Pase activity was caused by a decrease in the VE. In 3-month-old rats, the VE was increased 2,5-fold by treatment with T3, whereas triamcinolone or the two hormones in combination caused little effect; in 24-month-old animals, the VE was increased 10-fold by T3 and 2-fold by either triamcinolone or the two hormones in combination. In contrast, in 3-month-old animals, the VT was increased 2-fold by triamcinolone, 1.5-fold by T3, and 2-fold by the two hormones in combination; in 24-month-old animals, the VT was increased 3.5-fold by triamcinolone, was not affected by T3, and was increased 1.5-fold by the two hormones in combination. These differences could not be explained by changes in the response of isolated microsomes to sodium deoxycholate or by effects on the energy of activation of G-6-Pase. The results provide detailed evidence for an altered response to either T3 or triamcinolone in hepatocytes from old animals.
 ...
PMID:Age-related differences in the response of hepatic microsomal glucose-6-phosphatase to triiodothyronine and triamcinolone in the rat. 628 88

In the endothelial cells of capillaries in the rat CNS, we have observed abundant, circumferentially oriented, smooth, membrane-bound profiles, found just beneath, and parallel to, the abluminal plasmalemma. These structures are seen particularly well in tissue exposed to potassium ferricyanide-reduced OsO4. We studied these structures cytochemically, using glucose-6-phosphatase as a marker for endoplasmic reticulum, and acid phosphatase as a marker for the Golgi-associated endoplasmic reticulum containing lysosomal enzymes (GERL). We found that they contained glucose-6-phosphate hydrolyzing activity but did not contain acid phosphatase activity. Comparable structures were not seen in the continuous capillaries of skeletal muscle. Based on their morphology and content of glucose-6-phosphate hydrolyzing activity, we conclude that these structures are uniquely oriented smooth endoplasmic reticulum, which is much more abundant in capillaries of the CNS than in other continuous capillaries. The function of this distinctive feature of the CNS capillary is not known.
 ...
PMID:Abundant, uniquely oriented endoplasmic reticulum in capillaries of the CNS: demonstration using reduced-osmium and glucose-6-phosphatase cytochemistry. 629 74

Mice fed a sorbitol-enriched diet show measurable increases of alkaline phosphatase, glucose-6-phosphatase, and glucose-6-phosphate in the liver. The increases are positively correlated with duration of the sorbitol feeding program. The results could imply that sorbitol promotes glycogen synthesis.
 ...
PMID:Effect of dietary sorbitol on alkaline phosphatase and glucose-6-phosphatase in the mouse. 630 91

The endoplasmic reticulum (ER) and its contribution to the endomembrane system (i.e., membranes of cell organelles) in the neuron have been investigated in brains of mice by applying electron microscopic enzyme cytochemistry for demonstration of glucose-6-phosphatase (G6Pase) activity. The phosphohydrolytic activity of G6Pase is a well-known cytochemical marker for the ER in numerous cell types. Of the different substrates employed, glucose-6-phosphate and mannose-6-phosphate were the only two with which G6Pase reaction product was seen in the neuronal ER and organelles related morphologically to the ER. G6Pase activity in cell bodies and dendrites was localized consistently within the lumen of the nuclear envelope, rough and smooth ER, lamellar bodies, hypolemmal and subsurface cisternae, and frequently in the cis saccules of the Golgi apparatus. The G6Pase reactive ER appeared as a network of saccules and tubules pervading the cell body and its dendrites. Possible membrane continuities were identified between the ER and the other reactive structures, including the cis half of the Golgi apparatus. Neither G6Pase activity nor reactive ER was associated with the trans Golgi saccules or GERL. G6Pase activity thus serves as a reliable marker for the perikaryal and dendritic ER and related structures. These observations support the theory that the ER is an integral component of the neuronal endomembrane system associated with the transfer of membrane or membrane molecules among intracellular compartments, the packaging and transport of exportable protein, and energy metabolism. G6Pase activity in the ER of axons and terminals is considered in detail in part two of this study.
 ...
PMID:The neuronal endoplasmic reticulum: its cytochemistry and contribution to the endomembrane system. I. Cell bodies and dendrites. 630 51

Glycogen storage disease type Ib has all the clinical manifestations of glycogen storage disease type Ia such as hepatomegaly, growth retardation, bleeding tendency, hypoglycemia, hyperlactacidemia, hyperuricemia, hyperlipidemia, impaired platelet function plus neutropenia. The overall glucose-6-phosphatase activity in disrupted microsomes from liver is normal whereas glucose-6-phosphate translocase, the first enzyme in the glucose-6-phosphate transport system is absent. There is no glucose-6-phosphatase activity in vivo. Recent results show that in granulocytes the glucose-6-phosphate-dependent hexosemonophosphate-shunt is impaired.
 ...
PMID:Glycogen storage disease type Ib. 631 72

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.
 ...
PMID:Evidence for suppression of hepatic glucose-6-phosphatase with carbohydrate feeding. 631 14

Liver cells obtained from newborn mice homozygous for any one of several overlapping deletions in chromosome 7 fail to express a number of liver-specific differentiated traits. Among these is the activity of the membrane-bound liver-specific enzyme glucose-6-phosphatase (Glc-6-Pase; D-glucose-6-phosphate phosphohydrolase, EC 3.1.3.9). Previous studies have led to the suggestion that the region of the genome covered by these deletions includes genes that normally regulate the expression of structural genes encoding liver-specific enzymes and proteins mapping elsewhere in the genome. To find out whether the deficiency of Glc-6-Pase may be caused by the deletion of the relevant structural gene, mouse liver cells homozygous for the deletion c14CoS were hybridized with 2S Faza rat hepatoma cells, and the hybrid cell cultures were analyzed for mouse and rat Glc-6-Pase activity. Hybrids showed expression of mouse Glc-6-Pase activity, proving that the structural gene for this enzyme is not included in the deletion c14CoS in chromosome 7. In the hybrid cells the rat hepatoma genome apparently contributes a factor that activates the structural gene of the mouse and corrects its failure of expression, which most likely resulted from the deletion of an essential regulatory or processing gene. By using as a marker glucose-6-phosphate isomerase (Glc-6-PIase; glucosephosphate isomerase, D-glucose-6-phosphate ketolisomerase, EC 5.3.1.9), known to map on chromosome 7, this entire chromosome could be excluded as a possible carrier of the Glc-6-Pase structural gene. In addition, the structural genes for Glc-6-Pase and for tyrosine aminotransferase (TyrATase; L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5), another enzyme deficient in lethal deletion homozygotes, were shown to map on two different chromosomes. Together with our previous studies of TyrATase gene regulation, the present experiments suggest that the region of the mouse genome defined by the deletions includes one or more genes regulating the expression of several structural genes that map on different chromosomes and that encode liver-cell-type specific traits.
 ...
PMID:Correction of a genetically caused enzyme defect by somatic cell hybridization. 657 48

The relevance of our present findings should not rest on the possible role of mannose as an important teratogen in man. Excessive exposure to mannose during pregnancy via dietary intake seems unlikely since mannose is absorbed poorly from the gastrointestinal tract and intestinal hydrolysis of mannosidic linkages may be minimal. Moreover, although some plasma mannose may be generated continuously from endogenous sources via the cleavage of mannose-6-phosphate by hepatic glucose-6-phosphatase or mannosidic linkages by other hydrolases, our ongoing surveys have not uncovered any specimens of plasma or amniotic fluid containing mannose in amounts which could compete effectively with prevailing levels of glucose. Although we are continuing to monitor clinical samples for unusual mannose levels, we believe that the major significance of our experiences with this hexose pertains to its applications as a physiological tool for evaluating the metabolic determinants of early organogenesis. Within the above context, our findings must be viewed in relation to the known features of energy metabolism in the embryo during the interval that we have studied (Fig. 9). The classic studies of Shepherd and colleagues, similar findings by others, and more recent experiments in our own laboratory have indicated that glycolysis constitutes the chief energy source for the post-implantation embryo prior to the establishment of the yolk sac circulation on day 10 1/2. Almost all of the assimilated glucose goes to lactic acid, mitochondrial electron transfer is poorly developed, and oxidative metabolism via the Krebs' cycle is minimal. Meaningful Krebs' cycle activity does not become operative until day 10 1/2 and full expression is not found until the establishment of the allantoic circulation on day 11 (Fig. 9). The present experiences with mannose provide the first documentation of how precariously development is balanced during that transitory 9 1/2-10 1/2 day phase of organogenesis when glycolysis predominates. We have shown that even minor perturbations of glycolytic flux during that interval can result in major dysmorphogenic sequelae. Thus, the proposition by Kalter and Warkany that "any meaningful attempt to reduce infant mortality further will have to address the still unresolved causes of congenital malformations" prompts our speculation that major congenital lesions may result from relatively minor disturbances in glycolysis occurring prior to oxidative maturation in the embryo unit. Such effects on glycolysis during this vulnerable phase of embryogenesis could provide a common basis for the teratogenic actions of many unrelated and as yet unidentified agents.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:The honeybee syndrome: teratogenic effects of mannose during organogenesis in rat embryo culture. 667 63


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>