Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Effects of transformation by Rous sarcoma virus on sugar uptake and activity and the subcellular distribution of hexokinase isozymes in chick embryo fibroblasts were examined. Transformation caused a several-fold increase in the maximum velocity for uptake of 2-deoxyglucose without a significant change in Km. Cytochalasin B (CB), was used to differentiate between the effects of transformation on facilitated diffusion and the nonsaturable (CB-insensitive) mode. Transformation was found to stimulate 2-deoxyglucose transport by both mechanisms, but the increase in transport by the CB-insensitive mode was greater. Transformation enhances the activity of hexokinase, the enhancement being confined to the particulate fraction of the enzyme. Heat-inactivation and electrophoretic mobility studies showed that although hexokinase Type I is the major form in both normal and transformed fibroblasts, there is a significant increase in the proportion of the Type II isozyme in the transformed cells.
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PMID:Transport and phosphorylation of hexoses in normal and Rous sarcoma virus-transformed chick embryo fibroblasts. 21 96

Dexamethasone decreases 2-D-deoxyglucose (2-dGlc) uptake and accumulation into rat peritoneal macrophages in vitro in a concentration- and time-dependent manner (Ki for 1 microM-dexamethasone after a 2 h exposure = 0.71 +/- 0.21 microM; Ki for 0.1 microM-dexamethasone after exposure for 4 h = 0.10 +/- 0.06 microM). The inhibition of 2-dGlc uptake is consistent with a decrease in the coupling between endofacial hexokinase activity and the sugar transporter. The evidence for this is: (1) the Km for zero-trans 2-dGlc uptake in quiescent macrophages was increased by dexamethasone, but there was no significant effect on the Vmax.; (2) dexamethasone increased the rate of exit of sugar from cells preloaded with 2-dGlc; (3). the free sugar accumulation within the cytosol of the cells above the external solution concentration was significantly decreased by dexamethasone. These effects of dexamethasone on 2-dGlc transport were antagonized by simultaneous exposure to the steroid RU 38486 (Ki = 0.04 +/- 0.01 microM; 4 h incubation). Although dexamethasone inhibited zero-trans uptake, the maximum rate of infinite-trans exchange uptake of 2-dGlc into cells preloaded with 3-O-methyl-D-glucose (40 mM) was unaltered by dexamethasone or RU 38486, indicating that the dexamethasone-dependent decrease in zero-trans uptake was not due to a change in the number of transporters in the plasma membrane. Dexamethasone also inhibited the phorbol myristate acetate-induced stimulation of hexose monophosphate shunt (HMPS) activity, and this was reversed by RU 38486. Cytochalasin B, the potent sugar-transport inhibitor, inhibited HMPS activity and 2-d[2,6-3H]Glc uptake equally, indicating a single site of action. By contrast, dexamethasone showed differential inhibition of HMPS activity and 2-d[2,6-3H]Glc uptake, suggesting that it not only acts by decreasing the coupling between hexokinase and sugar transport, but also at one or more additional points.
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PMID:Dexamethasone inhibits the hexose monophosphate shunt in activated rat peritoneal macrophages by reducing hexokinase-dependent sugar uptake. 188 24

Phlorizin, phloretin and cytochalasin B are known to be specific sugar transport inhibitors. A study was made of their effects on the carbohydrate-protein interaction in solution as a model system for examining the initial steps of sugar membrane transport. Glycogen precipitation by concanavalin A is inhibited only by alpha-methylmannoside, whereas both phlorizin and phloretin inhibit interactions between hexokinase and glucose, and between glucose-6-phosphate dehydrogenase and glucose-6-phosphate. Cytochalasin B was found to exert no effect on both the concanavalin A--glycogen interaction and the enzyme reactions investigated. The data obtained in the model system examination may suggest that the sites of glucose and cytochalasin binding are, respectively, spatially uncoupled.
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PMID:[The action of inhibitors of sugar transport phlorizin, phloretin and cytochalasin B in model systems]. 271 59

2-Deoxyglucose and 3-O-methylglucose were used to assess endotoxin-induced changes in glucose transport in rat adipocytes. 6 h after Escherichia coli endotoxin injection insulin-stimulated 2-deoxyglucose uptake was significantly depressed (V decreased, Km unaltered), phosphorylation of 2-deoxyglucose was seemingly unimpaired; basal 3-methylglucose entry was significantly increased, insulin-stimulated uptake was unaltered. Insulin significantly reduced Km in control and endotoxin-treated cells. Cytochalasin B-insensitive uptake of both 2-deoxy-glucose and 3-methylglucose, a small fraction of total transport, increased significantly in endotoxic cells. Endotoxin reduced spermine- and insulin-stimulated 2-deoxyglucose uptake to a similar extent. Results are consistent with the hypotheses that (1) a site of endotoxin-induced insulin resistance is at the cell membrane level and may reflect a decrease in number of activity of effective carrier units, rather than alterations in affinity, (2) endotoxin does not compromise the hexokinase system, (3) the cell membrane-localized effect of endotoxin on hexose transport is not necessarily mediated by the insulin receptor and (4) the entry of 2-deoxyglucose and 3-methyl-glucose may involve two separate transport systems.
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PMID:Endotoxin-induced alterations in glucose transport in isolated adipocytes. 702 18

This study tests the hypothesis that glucose tolerance in fish is related to nutrient preference and is correlated with white muscle glucose transporter and phosphorylation (hexokinase) activities. Glucose clearance was investigated in the carnivorous rainbow trout (Oncorhynchus mykiss) and American eel (Anguilla rostrata) (feeding and fasting) and the omnivorous black bullhead catfish (Ameiurus melas). Glucose tolerance was assessed by an intravenous glucose tolerance test, injecting 250 mg glucose/kg body weight and tracking blood glucose concentrations over 24 h. Both feeding eel and feeding catfish returned plasma glucose levels to baseline within 60 min of glucose injection. Glucose values remained elevated for more than 360 min in both the food-deprived eel and the feeding rainbow trout. Glucose transport studies in white muscle membrane vesicles provided evidence for the presence of a stereospecific, saturable glucose transporter in all three species. Affinity constants (K(m)) ranged from 8 to 14 mM while V(max) values ranged from 75 to 150 pmol/s/mg protein. Neither kinetic parameter differed significantly between species. Cytochalasin B and phloretin did not significantly inhibit glucose transport, implying that these transporters are unlike the mammalian muscle glucose transporters (GLUT). In fact, Northern and Western blot analyses of mRNA and protein from white and red muscles and heart did not detect a mammalian-type GLUT-1 or -4 in any of the species examined. Glucose phosphorylation indicated the presence of a hexokinase activity (low K(m) enzyme) but again there were no differences in kinetic parameters between species. These studies demonstrate that glucose tolerance in fish is species-dependent but none of the parameters examined clearly differentiate between the species examined. Certainly a stereospecific glucose transporter exists in white skeletal muscle of the fish studied but no molecular or kinetic similarities to the mammalian GLUTs were found. Whether these transporters are insulin-sensitive or contribute to glucose tolerance requires further molecular characterization.
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PMID:Glucose tolerance and peripheral glucose utilization in rainbow trout (Oncorhynchus mykiss), American eel (Anguilla rostrata), and black bullhead catfish (Ameiurus melas). 1135 53

Fluorine-18-2-fluoro-2-deoxy-D-glucose (18F-FDG) injectable was developed as a tumor imaging agent reflecting glucose metabolism. In membrane transportation studies, the uptake of 14C-FDG into erythrocytes decreased with an increase in glucose concentration, and Cytochalasin B, inhibitor of glucose transporter (GLUT), blocked the uptake about 75%. The results means FDG is transported into tumor cells mainly by GLUT as glucose analogues. 18F-FDG is recognized to be phosphorylated to 18F-FDG-6-phosphate with hexokinase. We found that FDG-6-phosphate was further isomerized to 18F-FDM-6-phosphate by phosphoglucose isomerase (PGI) in vitro. About 27% 18F-FDM-6-phosphate was generated at the reaction with 70 U PGI for 90 min. These results show that the 18F-FDG injectable manufactured by the commercial supply system has equivalent properties; membrane transportation characteristic and enzyme affinity, to FDG synthesized at each PET institution.
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PMID:[Uptake of FDG (2-fluoro-2-deoxy-D-glucose) as a tumor imaging agent into erythrocytes and accumulation of FDG in tumor cells]. 1270 Dec 4