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

To investigate the antihyperglycaemic effect of metformin (dimethylbiguanide), insulin binding and glucose metabolism were examined in soleus muscles isolated from streptozotocin diabetic mice. Treatment with metformin (250 mg/kg/day orally for 3 weeks) reduced by 39% the severity of streptozotocin-induced hyperglycaemia. Soleus muscles of metformin treated mice showed a 41% increase in total insulin receptor number, and a 20% increase in 3-0-methylglucose uptake at both submaximally and maximally stimulating insulin concentrations. Oxidation of U-14C-glucose to 14CO2 and the formation of 14C-glycogen were increased by 25% and 30% respectively at maximally stimulating insulin concentrations, but not at submaximally stimulating concentrations. Lactate formation was not significantly altered. Maximum activity of hexokinase (EC 2.7.1.1) was increased by 35%, and this effect was independent of insulin. The results suggest that the antihyperglycaemic effect of metformin in streptozotocin diabetic mice is related in part to an increase in insulin-mediated glucose uptake and oxidative metabolism in skeletal muscle.
 ...
PMID:Effect of metformin on glucose metabolism in mouse soleus muscle. 377 Feb 75

Enzymes of the Embden-Meyerhof-Parnas pathway and hexose monophosphate shunt were examined in cytoplasmic extracts of three serovars of Ureaplasma urealyticum. We found no glucose-6-phosphate or 6-phosphogluconate dehydrogenase, hexokinase, phosphoglucose isomerase, aldolase, or lactic dehydrogenase activities. We failed to find cytochrome pigments in extracts and found no significant production of 14CO2 from [U-14C]glucose, nor did we find oxygen-dependent reduced nicotinamide adenine dinucleotide oxidase activity. Lactic acid was found only at trace levels in spent culture fluids. Ureaplasmas are apparently nonfermentative and are unlike all other mollicutes in that they have no detectable oxygen-dependent reduced nicotinamide adenine dinucleotide oxidase activity.
 ...
PMID:Metabolic distinctiveness of ureaplasmas. 379 29

1. Lactic acid formation in supernatant fractions of homogenates of cat or rat small-intestinal mucosa was measured under optimum conditions with glucose, fructose, glucose 6-phosphate, fructose 1,6-diphosphate or 3-phosphoglycerate as substrate. 2. Between 80 and 107% of the glycolytic activity of the homogenate was recovered in these particle-free preparations when glucose, fructose, glucose 6-phosphate or fructose 1,6-diphosphate was used as substrate. 3. Evidence was obtained that hexokinase and phosphofructokinase were the rate-limiting enzymes in the initial sequence of glycolytic reactions. The limitation of rate by hexokinase was much more pronounced in preparations from the cat than in those from the rat. 4. With subcellular preparations from cat or rat small intestine lactic acid was also formed from ribose 5-phosphate and at rates similar to those observed with glucose. 5. A higher rate of glycolysis was observed with glucose 6-phosphate as substrate with preparations from the proximal half of the small intestine of the rat as compared with the distal half. 6. Mucosal preparations from rats starved for 24-48hr. exhibited only about one-quarter of the glycolytic activity of those of fed control groups. The decreased rate of formation of lactic acid from either glucose or fructose was mainly due to a decrease in the activity of hexokinase(s). The activities of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase and a number of other enzymes were not significantly decreased by starvation. 7. The results are discussed in relation to metabolic control of glycolysis in other mammalian tissues.
 ...
PMID:Glucose metabolism in the mucosa of the small intestine. Glycolysis in subcellular preparations from the cat and rat. 429 Sep 84

1. Insulin deficiency induced by anti-insulin serum or streptozotocin increased glucose absorption, as measured in everted sacs of rat upper ileum incubated for 30 min with oxygenated Krebs-Henseleit bicarbonate medium.2. Everted sacs prepared from the terminal ileum of insulin-deficient rats were able to accumulate glucose against a concentration gradient (i.e. development of active glucose transport).3. In experimental diabetes induced by streptozotocin, everted sacs of upper ileum showed increased 3-methyl glucose active transport, and sacs of terminal ileum showed development of 3-methyl glucose active transport.4. Lactic acid formation during the absorption of both glucose and 3-methyl glucose was increased approximately twofold in everted sacs of insulin-deficient animals.5. Insulin added at 100 mu./ml. to the incubating media of everted sacs prepared from insulin-deficient rats did not result in a reduction of glucose absorption or reverse the other effects.6. Fluoride (5 x 10(-3)M) added to the serosal and mucosal media of sacs of terminal ileum prepared from insulin-deficient rats decreased [(14)C]CO(2) formation from [U-(14)C]glucose and lactate formation during glucose absorption, but was unable to reverse the effect of insulin deficiency on glucose active transport.7. The effects of insulin deficiency induced by streptozotocin were more striking than those induced by anti-insulin serum.8. Everted sacs prepared from rats starved for 3 days showed increased glucose active transport accompanied by diminished conversion of [U-(14)C]glucose to [(14)C]CO(2).9. The possible role of hexokinase is discussed in relation to these findings.
 ...
PMID:The effect of insulin and insulin deficiency on the transport and metabolism of glucose by rat small intestine. 555 73

Single canine Purkinje cells were isolated by microdissection and analyzed quantitatively for six enzymes of energy metabolism. Subendocardial Purkinje cells were clearly distinguishable morphologically and biochemically from adjacent myocardium and had enzyme levels comparable with extramural Purkinje cells. Oxidative enzymes, citrate synthase, malate dehydrogenase, and beta-hydroxyacyl CoA dehydrogenase were 40-60% lower in Purkinje cells than in myocardium. Lactate dehydrogenase was also 40% lower, but the other glycolytic enzymes, hexokinase and phosphofructokinase, were similar in level in myocardium and Purkinje cells. The results of this study show that it is completely practicable to apply quantitative histochemical analysis to biochemical study of the cardiac conducting system.
 ...
PMID:Quantitative histochemistry of canine cardiac Purkinje fibers. 622 55

The activities of various ammoniagenic, gluconeogenic, and glycolytic enzymes were measured in the renal cortex and also in the liver of rats made diabetic with streptozotocin. Five groups of animals were studied: normal, normoglycemic diabetic (insulin therapy), hyperglycemic, ketoacidotic, and ammonium chloride treated rats. Glutaminase I, glutamate dehydrogenase, glutamine synthetase, phosphoenolpyruvate carboxykinase (PEPCK), hexokinase, phosphofructokinase, fructose-1,6-diphosphatase, malate dehydrogenase, malic enzyme, and lactate dehydrogenase were measured. Renal glutaminase I activity rose during ketoacidosis and ammonium chloride acidosis. Glutamate dehydrogenase in the kidney rose only in ammonium chloride treated animals. Glutamine synthetase showed no particular variation. PEPCK rose in diabetic hyperglycemic animals and more so during ketoacidosis and ammonium chloride acidosis. It also rose in the liver of the diabetic animals. Hexokinase activity in the kidney rose in diabetic insulin-treated normoglycemic rats and also during ketoacidosis. The same pattern was observed in the liver of these diabetic rats. Renal and hepatic phosphofructokinase activities were elevated in all groups of experimental animals. Fructose-1,6-diphosphatase and malate dehydrogenase did not vary significantly in the kidney and the liver. Malic enzyme was lower in the kidney and liver of the hyperglycemic diabetic animals and also in the liver of the ketoacidotic rats. Lactate dehydrogenase fell slightly in the liver of diabetic hyperglycemic and NH4Cl acidotic animals. The present study indicates that glutaminase I is associated with the first step of increased renal ammoniagenesis during ketoacidosis. PEPCK activity is influenced both by hyperglycemia and ketoacidosis, acidosis playing an additional role. Insulin appears to prevent renal gluconeogenesis and to favour glycolysis. The latter would seem to remain operative in hyperglycemic and ketoacidotic diabetic animals.
 ...
PMID:Renal enzymes during experimental diabetes mellitus in the rat. Role of insulin, carbohydrate metabolism, and ketoacidosis. 623 75

In order to study the effect of insulin and epidermal growth factor (EGF) on glycolysis in quiescent 3T3 fibroblasts and their mechanisms of action, lactic acid produced by cells and activities of key glycolytic enzymes in cell extracts were determined. Insulin increased lactic acid production; the maximal stimulation occurred at the concentrations above 250 ng/ml and the half-maximal dose was 50 ng/ml. This effect of insulin appeared as early as one hour, and lactic acid production in the presence of insulin linearly increased up to 4 h. The 24-h pretreatment with insulin exhibited no significant effect on the production by cells afterward incubated either with or without insulin. Lactic acid production decreased as the concentration of phloridzin increased. However, insulin stimulation of the production still remained in the presence of phloridzin. Parahydroxymercuribenzoate reduced production only by the equivalent of the increase due to insulin. EGF also increased lactic acid production; this effect occurred at 1 ng/ml and was maximal at 100 ng/ml. The activities of hexokinase, phosphofructokinase and pyruvate kinase in quiescent cells were not increased by insulin, and the affinities for substrates of these enzymes remained unaltered. These findings suggest that glucose uptake is a rate-limiting step in glycolysis in quiescent 3T3 fibroblasts and that the stimulatory effect of insulin on glycolysis is mediated by enhanced glucose entry.
 ...
PMID:Insulin and epidermal growth factor stimulate glycolysis in quiescent 3T3 fibroblasts with no changes in key glycolytic enzyme activities. 623 8

Intracellular enzymes in erythrocytes can be made accessible for in situ kinetic studies by treating the cells with bifunctional reagents to crosslink proteins, thus creating a network that allows subsequent permeabilization by delipidation without escape of intracellular proteins. Dimethyl suberimidate, dimethyl 3,3'-dithiobispropionimidate, and toluene-2,4-diisocyanate have been used successfully as crosslinking reagents, and digitonin has been used for delipidation. In a systematic study of the in situ behavior of the 11 glycolytic enzymes of rat erythrocytes, it was observed that Km and Vmax values for the majority of the enzymes are essentially the same in situ as in vitro. Lactate dehydrogenase (L-lactate:NAD+ oxidoreductase, EC 1.1.1.27) is inhibited by excess of pyruvate as much in situ as in vitro. Hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) was allosterically inhibited by glucose 6-phosphate nearly as much in situ as in vitro but was not affected by 2,3-biphosphoglycerate. The allosteric properties of 6-phosphofructokinase (ATP:D-fructose 6-phosphate 1-phosphotransferase, EC 2.7.1.11), glyceraldehyde-phosphate dehydrogenase [D-glyceraldehyde-3-phosphate:NAD+ oxidoreductase (phosphorylating), EC 1.2.1.12], and pyruvate kinase (ATP: pyruvate 2-O-phosphotransferase, EC 2.7.1.40) in situ were qualitatively similar to those observed in vitro, but some important quantitative differences were noticed. Particularly striking was the much greater activity of phosphofructokinase in situ compared to that in vitro at physiological concentrations of effector metabolites.
 ...
PMID:Permeabilization of animal cells for kinetic studies of intracellular enzymes: in situ behavior of the glycolytic enzymes of erythrocytes. 645 Apr 16

The rate of oxidation of glucose is reduced in mouse embryos in the prolonged free living phase associated with delayed implantation and increases when the embryos are reactivated by estrogen. To determine how these changes in metabolism are regulated, several aspects of glucose metabolism were evaluated in dormant and reactivated blastocysts: 1) Embryos were exposed to 14C-pyruvate in vitro and evolved 14CO2 was measured. It was found that the rate of production of CO2 was equal in the two types of blastocysts, suggesting that aerobic pathways are fully functional during delayed implantation. 2) Production of lactate in the presence of O2 was measured and a decrease of 30% was found in delayed implanting embryos, suggesting that the overall regulatory mechanism for glucose metabolism resides in the glycolytic portion of the pathway. 3) Capacity for uptake and phosphorylation of glucose was evaluated using 3H-2-deoxyglucose and was found to be equal in the two types of embryos. 4) Total amounts of the rate-controlling enzymes for glycolysis (i.e., hexokinase and phosphofructokinase) in lysates of delayed and reactivated embryos were found to be equal, indicating that amounts of these enzymes are not limiting in delayed implantation. 5) Lactate production, measured under anaerobic conditions, was found to be equal, demonstrating that it is not the capacity for glycolysis but a difference in the degree of allosteric inhibition that is responsible for reduced glucose oxidation in delayed implantation. 6) Levels of ATP, ADP, and hexose-6-phosphates were found to be consistent with allosteric inhibition of the glycolytic pathway at phosphofructokinase during delay and a release of this inhibition with reactivation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Regulation of glycolysis in the mouse blastocyst during delayed implantation. 647 Jun 45

It has been found that calf eyes are an excellent source of trabecular meshwork tissue for biochemical studies. Homogenates of pooled meshwork were centrifuged at 27K X g and 1.5K X g. The high-speed supernatants produced lactate at 0.35 mumole/min/gm tissue in the presence of hexokinase-saturating concentrations of glucose (10 mM) at pH 7. The optimum pH was 7.6. In the absence of ammonia, lactate could be produced from fructose 1,6-diphosphate but not from glucose or glucose 6-phosphate. The optimum ammonia concentration was 1 to 2 mM. Lactate was produced at an even greater rate from fructose, but only poorly from sorbitol or galactose (all at 10 mM). The activity of hexokinase, glucose 6-phosphate dehydrogenase and UDPG dehydrogenase was measured. Fructokinase could not be detected. The low-speed supernatant readily oxidized succinate, malate, and glutamate at about 0.012 muAtO/min/gm tissue. The oxidative rate in vivo is estimated to be about one third of this. These results demonstrate that knowledge of the normal metabolism of calf trabecular meshwork may be obtained with relative ease, with possible important implications for understanding the disease of glaucoma.
 ...
PMID:Metabolism of calf trabecular (reticular) meshwork. 735 Jan 29


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