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:2.7.1.1 (hexokinase)
5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carbohydrate intolerance was investigated in 8 alcoholics with liver cirrhosis and in controls. Indices of carbohydrate metabolism, glucose and insulin levels after glucose loading, were compared with glucose phosphorylating (glucokinase, hexokinase) and releasing (glucose-6-phosphatase) enzymes. Comparison was also made with pericellular collagen in liver biopsies and with insulin sensitivity assessed by the euglycemic clamp technique and with conventional liver function tests including oral antipyrine test. Glucokinase activity was low or absent, hexokinase activity increased and the GK/HK ratio reduced. Glucose-6-phosphatase activity was lowered and insulin sensitivity decreased. Pericellular collagen was increased (P less than 0.001) and related to the fasting glucose (r0.593) and insulin levels (r0.526). Blood glucose was related to antipyrine metabolism (r-0.727) but not to the other liver tests. Glucose intolerance in cirrhosis seems to be associated with reduced glucose phosphorylating and liberating enzyme activities. Hyperinsulinaemia, developing secondarily, may then lead to insulin resistance.
...
PMID:Carbohydrate intolerance associated with reduced hepatic glucose phosphorylating and releasing enzyme activities and peripheral insulin resistance in alcoholics with liver cirrhosis. 299 23

Characterization of glucokinase in pancreatic B-cells from ob/ob mice and from rat liver revealed identical characteristics. A narrow substrate specificity; high Km values for the two substrates, D-glucose and D-mannose, in the range of 10 and 20 mmol/l, respectively; higher Vmax values for D-glucose than for D-mannose; inhibition of glucokinase activities by D-mannoheptulose and by a specific glucokinase antibody. These characteristics distinguish glucokinase in soluble cytoplasmic fractions of pancreatic B-cells and liver from low Km hexokinases. Alloxan is a pancreatic B-cell cytotoxic agent, which has been widely used as a tool for the elucidation of the mechanisms of insulin secretion, because its inhibitory action on insulin secretion has been presumed to be intimately related to the mechanism of glucose-induced insulin secretion. Alloxan inhibited glucokinase but not hexokinase activity in cytoplasmic fractions of pancreatic B-cells and liver. The half maximal inhibitory concentration of alloxan was 5 mumol/l. Glucokinase activity was protected from alloxan toxicity only by D-glucose and D-mannose; the alpha anomer of D-glucose provided significantly greater protection than the beta anomer. The non-metabolizable sugar 3-O-methyl-D-glucose did not provide protection of glucokinase activity against inhibition by alloxan. Thus, inhibition of pancreatic B-cell glucokinase may contribute to the inhibition of glucose-induced insulin secretion by alloxan. These results support the contention that glucokinase regulates the metabolic flux rate through the glycolytic chain in the pancreatic B-cell and thereby generates the signal for glucose-induced insulin secretion.
...
PMID:Glucokinase in pancreatic B-cells and its inhibition by alloxan. 329 98

The tissue distribution of glucokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) was examined by protein blotting analysis. Antibodies raised against rat liver glucokinase recognized a single protein subunit with an apparent Mr of 56,500 on nitrocellulose blots of cytosol protein from liver, separated by sodium dodecyl sulfate/polyacrylamide gel electrophoresis. A protein of identical electrophoretic mobility was detected by immunoblotting of cytosol protein from pancreatic islets. Hepatic glucokinase and the immunoreactive islet product bound to and were eluted from DEAE-cellulose at the same ionic strength. Glucokinase was displayed as a set of two spots with apparent pI values of 5.54 and 5.64 by immunoblotting after two-dimensional gel electrophoresis. The two isoforms appeared equally abundant in liver extract, whereas the component with a pI of 5.64 was predominant in islets. By quantitative immunoblotting, glucokinase was estimated to represent 0.1% of total cytosol protein in liver and 1/20th as much in islets. The glucokinase activity of both liver and islet cytosols was suppressed by the antibodies to hepatic glucokinase. Immunoblotting of cytosol protein from intestinal mucosa, exocrine pancreas, epididymal adipose tissue, kidney, brain, and spleen failed to reveal the glucokinase protein. Thus, significant expression of the glucokinase gene appears restricted to the liver and pancreatic islets.
...
PMID:Tissue-specific expression of glucokinase: identification of the gene product in liver and pancreatic islets. 351 42

M. Kuwajima, C. B. Newgard, D. W. Foster, and J. D. McGarry (1986, J. Biol. Chem. 261, 8849-8853) have concluded that the reason postprandial hepatic glycogenesis occurs primarily from gluconeogenic precursors rather than glucose is because glucokinase activity is insufficient to support the observed rates of glycogen synthesis. F. L. Alvares and R. C. Nordlie (1977, J. Biol. Chem. 252, 8404-8414) have concluded that the combined activities of glucokinase and hexokinase are less than the apparent rates of hepatic glucose uptake. We have identified several factors in the assays used in these studies which lead to substantial underestimations of glucokinase activity. Glucokinase was assayed either by allowing glucose 6-phosphate to accumulate over 10 min (discontinuous assay) or by coupling the formation of glucose 6-phosphate with its oxidation by Leuconostoc mesenteroides glucose 6-phosphate dehydrogenase and NAD (continuous assay). Accurate determinations of glucokinase at 37 degrees C with subsaturating glucose require both 100 mM KCl and 2.5 mM dithioerythritol in the assay medium; 2-mercaptoethanol will not substitute for dithioerythritol. When both KCl and dithioerythritol are absent (Kuwajima et al.) glucokinase activity is underestimated by 3- to 5-fold. The discontinuous assay as used previously (Alvares and Nordlie) underestimates glucokinase activity in crude extracts by 2- to 2.5-fold, due in part to the hydrolysis of glucose 6-phosphate and its transformation to other hexose monophosphates. Under optimized conditions at 37 degrees C both assays yield similar results in extracts from fed rats, i.e., 2-3 and 4-5 units/g liver at 10 and 100 mM glucose, respectively. Some implications of the finding that total hepatic glucose phosphorylating capacity at physiological concentrations significantly exceeds the observed rates of postprandial glycogen synthesis are discussed.
...
PMID:Factors underlying significant underestimations of glucokinase activity in crude liver extracts: physiological implications of higher cellular activity. 381 60

Glucokinase (ATP:D-glucose 6-phosphotransferase, EC 2.7.1.1) plays a pivotal role in hepatic glucose metabolism and serves as the glucose sensor in pancreatic islet beta-cells. Biochemical studies of this enzyme are complicated by the cellular heterogeneity of the liver and the pancreas and because the presence of hexokinases (ATP:D-hexose 6-phosphotransferases, EC 2.7.1.1) seriously interferes with currently available analytical procedures. A radiometric assay was designed to deal with these problems. It is based on the liberation of 3H2O from D-[2-3H(N)]glucose 6-phosphate, the product of the glucokinase reaction, using exogenous phosphoglucose isomerase (D-glucose-6-phosphate ketol-isomerase, EC 5.3.1.9). Interference by hexokinases was largely eliminated by using glucose 6-phosphate as inhibitor and the sensitivity of the assay was greatly increased by using small volumes with the oil well procedure. The assay was sufficiently sensitive to detect about 1 pg of glucokinase. It thus allowed the application of quantitative histochemical procedures to the study of intralobular hepatic glucokinase profiles and the pancreatic beta-cell glucose sensor. The quantitative histochemical procedures were sufficiently sensitive and reliable for measuring important kinetic constants of glucokinase (i.e., the Km and the Hill number) in microscopic samples of tissue.
...
PMID:Radiometric oil well assay for glucokinase in microscopic structures. 388 80

Three glucose-phosphorylating enzymes were separated from cell-free extracts of Saccharomyces cerevisiae by hydroxylapatite chromatography. Variations in the amounts of these enzymes in cells growing on glucose and on ethanol showed that hexokinase PI was a constitutive enzyme, whereas synthesis of hexokinase PII and glucokinase were regulated by the carbon source used. Glucokinase proved to be a glucomannokinase with Km values of 0.04 mM for both glucose and mannose. D-Xylose produced an irreversible inactivation of the three glucose-phosphorylating enzymes depending on the presence or absence of ATP. Hexokinase PI inactivation required ATP, while hexokinase PII was inactivated by D-xylose without ATP in the reaction mixture. Glucokinase was protected by ATP from this inactivation. D-Xylose acted as a competitive inhibitor of hexokinase PI and glucokinase and as a non-competitive inhibitor of hexokinase PII.
...
PMID:Inhibition and inactivation of glucose-phosphorylating enzymes from Saccharomyces cerevisiae by D-xylose. 390 28

1. Measurements were made of the activities of enzymes of the pentose phosphate cycle, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, ribose 5-phosphate isomerase, ribulose 5-phosphate epimerase, transketolase and transaldolase, as well as of the related or competing enzymes glucokinase, hexokinase, phosphoglucose isomerase and phosphoglucomutase, in control rats and in rats bearing the growth-hormone- and prolactin-secreting pituitary tumour MtTW5, to study the effect of high endogenous concentrations of growth hormone on this pathway in liver. 2. There was a twofold increase in liver weight. Glucokinase activity/g. of liver decreased to half the control value in the experimental group, although on a total liver basis it remained unchanged. Hexokinase activity increased in parallel with the liver weight, so that the total activity was doubled in rats with a high endogenous concentration of growth hormone. No differences in response were found between heat-stable and heat-labile forms of hexokinase. 3. The activity/g. of liver of the two oxidative enzymes of the pathway decreased slightly in the experimental group, but this was offset by the increase in liver weight, and the resultant effect was a 50% increase in the total activity. 4. Of the non-oxidative enzymes of the cycle the most marked increase on a total liver basis was in ribose 5-phosphate isomerase activity, to 2.5 times the control value. Ribulose 5-phosphate epimerase activity showed the smallest increase. Transketolase and transaldolase activities were also increased. The latter is the rate-limiting enzyme of the non-oxidative reactions of the cycle in these animals. 5. The results are discussed in relation to the glycolytic pathway and synthesis of glycogen, and more particularly to the increased requirement for ribose 5-phosphate for RNA synthesis.
...
PMID:The pentose phosphate pathway of glucose metabolism. Influence of a growth-hormone-secreting pituitary tumour on the oxidative and non-oxidative reactions of the cycle in liver. 580 93

1. Glucokinase and hexokinase activities have been determined in the livers of newborn rats and attempts made to influence in vivo the development of the glucokinase. 2. Glucokinase first appears in rat liver about 16 days after birth and adult activities are reached 10-12 days later. Evidence is presented which indicates that this represents synthesis of new protein. Hexokinase activities remain constant throughout the period of glucokinase development. 3. Both exogenous glucose and insulin are necessary for the natural development of glucokinase, for this is retarded in starved and alloxan-diabetic neonatal rats. 4. The absence of glucokinase during the first 2 weeks of extrauterine life in the rat is not due to lack of insulin. 5. Attempts to advance the time at which glucokinase first appears by infusions of glucose, insulin and chlorpropamide alone and in various combinations have resulted in marginal effects only. 6. When rats are starved for 3 days during the period of glucokinase development and then re-fed, glucokinase is more rapidly synthesized, indicating that the potential ability to synthesize glucokinase continues to develop throughout the period of starvation. 7. Some possible reasons for the comparatively late development of glucokinase are discussed.
...
PMID:The development of hepatic glucokinase in the neonatal rat. 588 29

Histochemical and immunohistochemical procedures have been used to examine the localization of three of the four hexokinase isoenzymes present in the liver of fed female Wistar rats. Distinctive distribution patterns were found for hexokinase type I and glucokinase but hexokinase type II was not detectable. Hexokinase type I was identified in sinusoidal cells and in bile duct epithelia, nerves and arteries in the portal triad. Glucokinase, the major isoenzyme, was confined to parenchymal cells where it was present in much higher amounts in perivenous compared with periportal hepatocytes. Staining within these two zones was not homogeneous and each had a mosaic appearance caused by the presence of a few hepatocytes containing little or no glucokinase amongst the majority of darkly stained cells in perivenous areas and a few darkly stained cells amongst the majority of unstained cells in periportal areas. Hence, hepatocytes in situ are a strikingly heterogeneous population of cells. Their metabolic status cannot be controlled simply by the differential supply of oxygen, substrates and hormones to different regions of the liver acini as proposed in the metabolic zonation model. Phenotypic differences may exist between cells within a given metabolic zone which influence their ability to respond to different environmental conditions.
...
PMID:Histochemical and immunohistochemical localization of hexokinase isoenzymes in normal rat liver. 609 98

Activities of key enzymes in hepatic glucose utilization were compared between obese (C57BL/6J ob/ob) mice, their lean controls and outbred Swiss albino mice in the fed condition and during fasting. As liver hyperplasia and hepatocyte hypertrophy were present in the ob/ob mice at 4-5 months of age and changes in hepatic cellularity did occur with fasting, enzyme activity was expressed on the basis of protein, DNA, and wet weight. In the fed state, activities of glucokinase + hexokinase (glucose phosphorylating capability), phosphofructokinase and pyruvate kinase were significantly greater in livers of ob/ob mice when compared to those of the lean control. Glucokinase + hexokinase activities in livers of ob/ob mice remained significantly higher throughout the 48 h fast yet the activities of hepatic phosphofructokinase and pyruvate kinase, when expressed per g wet wt or mg protein, decreased so that a statistical difference from the fasted lean control was no longer detected. When expressed per 100 g body weight, hepatic glucokinase + hexokinase as well as phosphofructokinase and pyruvate kinase activities in obese mice were higher both in the fed and fasted states when compared to lean controls in the comparable nutritional condition. This increased capacity of key enzyme activities in hepatic glucose utilization can be attributed to liver hyperplasia found in ob/ob mice in both the fed and fasted condition. While higher hepatic glucose phosphorylating capability was maintained during fasting, the elevated specific activities of hepatic phosphofructokinase and pyruvate kinase in the obese mouse in the fed state decreased with starvation to values found in the lean control.
...
PMID:Enzyme activities of hepatic glucose utilization in the fed and fasting genetically obese mouse at 4-5 months of age. 624 16


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

---