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

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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)

The ultrastructure of dog cardiomyocytes was studied one month after reproducing alloxan diabetes, with respect to myocardial extraction from the blood of glucose, nonesterified fatty acids, beta-lipoproteins and ketone bodies as well as to respiration in conjunction with oxidative phosphorylation of mitochondria, hexokinase and phosphorylase activity. Destructive changes in mitochondria, increased glycogen content in cardiomyocytes were revealed in the absence of glucose consumption by the myocardium which absorbed only lipoid metabolites. Lipoid inclusions were rarely seen in cardiomyocytes. The myocardium showed the increased content of lysosomes and hydrolytic phosphorylase. It is suggested that lipoid metabolites transform to glycogen, with lysosomes participating in the process.
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PMID:[Ultrastructural manifestations of early metabolic disorders in the myocardium of dogs with alloxan diabetes]. 739 46

S-methyl cysteine sulphoxide (SMCS), a sulphur containing amino acid isolated from onion (Allium cepa Linn) showed antidiabetic and antihyperlipidemic effects. Oral administration of SMCS daily at a dose of 200 mg/kg body weight for a period of 45 days to alloxan diabetic rats controlled significantly their blood glucose and lipids in serum and tissues and altered the activities of liver hexokinase, glucose 6-phosphatase and HMG CoA reductase towards normal. The above effects of SMCS were comparable to those of glibenclamide and insulin.
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PMID:Antidiabetic and hypolipidemic effects of S-methyl cysteine sulfoxide isolated from Allium cepa Linn. 766 95

A trial has been performed of a new sweetening agent saccharol, glycosides complex, on energy metabolism in rats with experimental alloxan diabetes. Elevated glucose level observed in rats with insulin insufficiency was associated with hexokinase activity inhibition and changes in the activity of the enzymes involved in glucose-6-phosphate transformation: enhanced activity of glucose-6-phosphatase and glucose-6-phosphate dehydrogenase against inhibition of phosphoglucomutase activity. Introduction of saccharose aggravated the above shifts in the rat liver, whereas saccharol possesses a protective action on hexokinase hepatic reaction and enzymes of glucose-6-phosphate conversion, reduced blood glucose. Positive changes induced by saccharol on energy metabolism in animals with insulin insufficiency can be attributed to the effect of saccharol glycosides.
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PMID:[Effect of saccharol glycosides on energy metabolism in animals with abnormal carbohydrate tolerance]. 797 8

Alloxan causes diabetes in experimental animals through its ability to destroy the insulin-secreting B-cells of the pancreas. Alloxan is hydrophilic and chemically unstable; it is reactive toward thiols, undergoing redox cycling in the presence of glutathione and oxidizing protein-bound thiol groups, as reflected by inhibition of the thiol enzymes, hexokinase and glucokinase. It is apparently also selectively taken up by the GLUT-2 glucose transporter in the pancreatic B-cell membrane. In order to investigate which, if any, of these physicochemical properties are important in the toxic action of alloxan, we have examined seven N-alkyl substituted alloxan derivatives of various diabetogenic activity. Hydrophilicity was identified as a factor essential for diabetogenicity. Stability, rate of redox cycling and reactivity toward thiol groups were not correlated with diabetogenicity. Selective uptake by the GLUT-2 glucose transporter is not a prerequisite for the diabetogenicity of alloxan derivatives.
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PMID:The relationship between the physicochemical properties and the biological effects of alloxan and several N-alkyl substituted alloxan derivatives. 825 88

Diabetic subjects present high susceptibility to infections but the mechanisms involved are not fully known. Macrophages and lymphocytes utilize glucose and glutamine at high rates and these metabolites are important for the function of these cells. The present study examines the activities of key metabolic enzymes in macrophages and lymphocytes obtained from alloxan-diabetic Wistar rats (10 weeks old, 7 rats each group). Since the enteral diet was enriched with omega-6 polyunsaturated fatty acids (PUFA), the effect of these fatty acids was also investigated in the same animals. Diabetes caused a marked decrease of hexokinase activity (48%; 274.23 +/- 18.43 vs 143.29 +/- 10.35 units for control vs diabetic rats) in macrophages and of citrate synthase and glucose-6-phosphate dehydrogenase activities (70%; 321.76 +/- 9.18 vs 96.25 +/- 5.43 units for citrate synthase and 89.43 +/- 2.33 vs 23.13 +/- 1.09 units for G6PDh for control vs diabetic rats) in mesenteric lymph node lymphocytes. A PUFA-rich diet given for 6 weeks enhanced hexokinase activities by 30% (274.23 +/- 18.43 vs 342.48 +/- 15.39, balanced vs PUFA-rich diets for normal and 143.29 +/- 10.35 vs 189.67 +/- 9.57 for diabetic rats) and reduced citrate synthase activities by 43% (30.31 +/- 1.73 vs 17.42 +/- 0.95, balanced vs PUFA-rich diets for normal and 29.34 +/- 1.23 vs 16.73 +/- 1.02 for diabetic rats) in macrophages, and reduced (< 50%; 59.67 +/- 3.45 vs 48.87 +/- 3.37 for hexokinase and 321.76 +/- 2.33 vs 161.66 +/- 9.97 for citrate synthase, balanced vs PUFA-rich diets) the activities of both enzymes in lymphocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of a polyunsaturated fatty acid-rich diet on macrophage and lymphocyte metabolism of diabetic rats. 829 16

Administration of sodium orthovanadate to diabetic animals exhibits insulin-like effects and has been effective in the reversal of biochemical complications. This study evaluates the effect of sodium orthovanadate (0.6 mg/ml) treatment for 21 days on the hepatic glucose homeostasis and lipid metabolism in alloxan diabetic rats. The activities of two lipogenic enzymes, glucose-6-phosphate dehydrogenase and malic enzyme; and related enzymes, hexokinase and glucose-6-phosphatase were measured in the liver cytosolic fractions of diabetic rats and diabetic rats treated separately with insulin and sodium orthovanadate. The total lipids, triglycerides and cholesterol levels were estimated in the livers of the diabetic and the treated rats. The activities of both the lipogenic enzymes and hexokinase isozymes were significantly decreased, whereas the activity of glucose-6-phosphatase was significantly increased in the diabetic liver. During diabetes, the levels of total lipids and triglycerides increased significantly with a decrease in the cholesterol levels in the liver. Insulin and vanadate were able to restore the altered enzyme activities to almost control levels. Both insulin and vanadate were found to partially restore the altered levels of total lipids, triglycerides and cholesterol in the livers of diabetic rats. The results indicate that vanadate administration to diabetic animals normalizes blood glucose and causes marked improvement of altered lipid metabolism during diabetes. The present study and earlier reports suggest the possible use of vanadate as insulin replacement in the therapy of diabetes when administered at pharmacological doses.
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PMID:Change in the lipid profile, lipogenic and related enzymes in the livers of experimental diabetic rats: effect of insulin and vanadate. 1058 Jun 9

The low-affinity glucose phosphorylating enzyme glucokinase has the function of a physiological glucose sensor in pancreatic beta cells and in liver. In contrast to the high-affinity hexokinase types I-III glucokinase shows extraordinary sensitivity toward SH group oxidizing compounds. To characterize the function of sulfhydryl groups cysteine residues in the vicinity of the sugar binding site (Cys 213, Cys 220, Cys 230, Cys 233, and Cys 252) as well as cysteine residues a distance from the active site (Cys 364, Cys 371, and Cys 382), they were replaced in human beta cell glucokinase by serine through site-directed mutagenesis. Controlled proteolysis of wild-type glucokinase by proteinase K revealed that the SH group oxidizing agent alloxan can induce the formation of multiple intramolecular disulfide bridges corresponding to a double-band pattern of glucokinase protein in nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The formation of intramolecular disulfide bridges altered the mobility of the protein. None of the cysteine mutations could prevent the formation of the 49-kDa glucokinase conformation after alloxan treatment. The cysteine mutants Cys 233, Cys 252, and Cys 382 showed nearly complete loss of catalytic activity, whereas the V(max) values of the Cys 213, Cys 220, Cys 364, and Cys 371 mutants were decreased by 30-60%. Only the Cys 230 mutant showed kinetic characteristics comparable to those of wild-type glucokinase. The sensitivity of the Cys 213, Cys 230, Cys 364, and Cys 371 mutants toward alloxan-induced inhibition of enzyme activity was up to 10-fold lower compared with wild-type glucokinase. d-Glucose and dithiotreitol provided protection against alloxan-induced inhibition of wild-type glucokinase and all catalytically active cysteine mutants. Conclusively our data demonstrate the functional significance of the cysteine residues of beta cell glucokinase for both structural instability of the enzyme and catalytic function. Knowledge of sensitive cysteine targets may help to develop strategies that improve glucokinase enzyme function under conditions of oxidative stress.
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PMID:Importance of cysteine residues for the stability and catalytic activity of human pancreatic beta cell glucokinase. 1070 Mar 81

Tinospora cordifolia is widely used in Indian Ayurvedic medicine for treating diabetes mellitus. Oral administration of an aqueous T. cordifolia root extract (TCREt) to alloxan diabetic rats caused a significant reduction in blood glucose and brain lipids. The extract caused an increase in body weight, total haemoglobin and hepatic hexokinase. The root extract also lowers hepatic glucose-6-phosphatase and serum acid phosphatase, alkaline phosphatase, and lactate dehydrogenase in diabetic rats. Thus TCREt has hypoglycaemic and hypolipidaemic effect.
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PMID:Hypoglycaemic and other related actions of Tinospora cordifolia roots in alloxan-induced diabetic rats. 1072 Jul 84

Aavirai Kudineer (AK) is an herbal decoction of seven botanical drugs, cited in the Gunapadam; a Tamil Siddha medical text. The anti-diabetic efficacy of this formulation was evaluated using alloxan-induced diabetic and normal rats. Glucose tolerance was observed within 1 hr in AK-treated rats (10 ml/kg body ) as compared to control. A significant decrease in the severe hyperglycemia characteristic of alloxan diabetes was noted after 15 days of AK treatment. Further AK treatment reversed the elevated urea, creatinine, cholesterol and decreased protein values to near normal levels. Assay of glycogen content and chief carbohydrate-metabolizing enzymes, viz. hexokinase, glucose-6-phosphatase and fructose 1,6 diphosphatase in the liver of diabetic and AK-treated diabetic rats clearly ascertains the hypoglycemic efficacy of this formulation. The mode of action of this herbal formulation remains to be elucidated.
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PMID:Biochemical studies on hypoglycemic effect of Aavirai kudineer: a herbal formulation in alloxan diabetic rats. 1183 78

We evaluated the effect of sodium molybdate on carbohydrate metabolizing enzymes and mitochondrial enzymes in diabetic rats. Diabetic rats showed a significant reduction in the activities of glucose metabolising enzymes like hexokinase, glucose-6-phosphate dehydrogenase, glycogen synthase and in the level of glycogen. An elevation in the activities of aldolase, glucose-6-phosphatase, fructose 1,6- bisphosphatase, glycogen phosphorylase and in the level of blood glucose were also observed in diabetic rats when compared to control rats. The activities of mitochondrial enzymes isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, NADH-dehydrogenase and cytochrome-C-oxidase were also significantly lowered in diabetic rats. Molybdate administration to diabetic rats reversed the above changes in a significant manner. From our observations, we conclude that administration of sodium molybdate regulated the blood sugar levels in alloxan-induced diabetic rats. Sodium molybdate therapy not only maintained the blood glucose homeostasis but also altered the activities of carbohydrate metabolising enzymes. Molybdate therapy also considerably improved the activities of mitochondrial enzymes, thereby suggesting its role in mitochondrial energy production.
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PMID:Effect of sodium molybdate on carbohydrate metabolizing enzymes in alloxan-induced diabetic rats. 1183 16


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