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)

Decavanadate inhibits hexokinase, adenylate kinase and phosphofructokinase; neither mono-, tri nor tetrameric vanadate anion is an inhibitor. Decavanadate inhibits phosphofructokinase obtained from bacterial and protistic sources. No form of vanadium(V) anion inhibits galacto-, glycero-, pyruvate and creatine kinase, or inorganic pyrophosphatase. Decavanadate appears to be a non-competitive inhibitor of both hexokinase substrates.
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PMID:Do vanadate polyanions inhibit phosphotransferase enzymes? 298 13

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.
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PMID:Vanadate: a potent inhibitor of multifunctional glucose-6-phosphatase. 627 21

Vanadium compounds are potent in controlling elevated blood glucose levels in experimentally induced diabetes. However the toxicity associated with vanadium limits its role as therapeutic agent for diabetic treatment. A vanadium compound sodium orthovanadate (SOV) was given to alloxan-induced diabetic Wistar rats in lower doses in combination with Trigonella foenum graecum, a well-known hypoglycemic agent used in traditional Indian medicines. The effect of this combination was studied on lens morphology and glucose metabolism in diabetic rats. Lens, an insulin-independent tissue, was found severely affected in diabetes showing visual signs of cataract. Alterations in the activities of glucose metabolizing enzymes (hexokinase, aldose reductase, sorbitol dehydrogenase, glucose-6-phosphate dehydrogenase) and antioxidant enzymes (glutathione peroxidase, glutathione reductase) besides the levels of related metabolites, [sorbitol, fructose, glucose, thiobarbituric acid reactive species (TBARS) and reduced glutathione (GSH)] were observed in the lenses from diabetic rats and diabetic rats treated with insulin (2 IU/day), SOV (0.6 mg/ml), T. f. graecum seed powder (TSP, 5%) and TSP (5%) in combination with lowered dose of vanadium SOV (0.2 mg/ml), for a period of 3 weeks. The activity of the enzymes, hexokinase, aldose reductase and sorbitol dehydrogenase was significantly increased whereas the activity of glucose-6-phosphate dehydrogenase, glutathione peroxidase and glutathione reductase decreased significantly in lenses from 3 week diabetic rats. Significant increase in accumulation of metabolites, sorbitol, fructose, glucose was found in diabetic lenses. TBARS measure of peroxidation increased whereas the levels of antioxidant GSH decreased significantly in diabetic condition. Insulin restored the levels of altered enzyme activities and metabolites almost to control levels. Sodium orthovanadate (0.6 mg/ml) and Trigonella administered separately to diabetic animals could partially reverse the diabetic changes, metabolic and morphological, while vanadate in lowered dose in combination with Trigonella was found to be the most effective in restoring the altered lens metabolism and morphological appearance in diabetes. It may be concluded that vanadate at lowered doses administered in combination with Trigonella was the most effective in controlling the altered glucose metabolism and antioxidant status in diabetic lenses, these being significant factors involved in the development of diabetic complications, that reflects in the reduced lens opacity.
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PMID:Efficacy of lower doses of vanadium in restoring altered glucose metabolism and antioxidant status in diabetic rat lenses. 1588 58

Vanadium has been reported to have broad pharmacological activity both in vitro and in vivo. Vanadium compound, sodium orthovanadate, Na3VO4, is well known for its hypoglycaemic effects. However, Na3VO4 exerts these effects at relatively high doses (0.6 mg/ml) and exhibit several toxic effects. In the present study lower doses of Na3VO4 (0.2 mg/ml) are combined with Trigonella foenum graecum seed powder (TSP), another hypoglycaemic agent, to reduce its toxicity without compromising its antidiabetic potential. The efficacy of the lower doses of Na3VO4 has been investigated in restoring the altered glucose metabolism and histological structure in the sciatic nerves in 21 and 60 days alloxan diabetic rats. A portion of the glucose was found to be channelled from the normal glycolytic route to polyol pathway, evident by the reduced hexokinase activity and increased polyol pathway enzymes aldose reductase and sorbitol dehydrogenase activity causing accumulation of sorbitol and fructose in diabetic conditions. Ultrastructural observation of the sciatic nerve showed extensive demylination and axonal loss after eight weeks of diabetes induction. Blood glucose levels increased in diabetic rats were normalized with the lower dose of vanadium and Trigonella treatment. The treatment of the diabetic rats with vanadium and Trigonella prevented the activation of the polyol pathway and sugar accumulations. The sciatic nerves were also protected against the structural abnormalities found in diabetes with Trigonella foenum graecum as well as Na3VO4. Results suggest that lower doses of Na3VO4 may be used in combination with TSP as an efficient antidiabetic agent to effectively control the long-term complications of diabetes in tissues like peripheral nerve.
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PMID:Restoration of ultrastructural and biochemical changes in alloxan-induced diabetic rat sciatic nerve on treatment with Na3VO4 and Trigonella--a promising antidiabetic agent. 1618 85

Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to abnormalities in either insulin secretion or action. A range of vanadium complexes have been synthesized and demonstrated to be effective in lowering hyperglycemia. Thiamine administration was also reported to prevent deterioration in fasting glucose and insulin levels, and to improve glucose tolerance in hyperglycemic patients. This study has been conducted to evaluate the ionic vanadyl(II) thiamine hydrochloride complex (VC) as a new anti-diabetic candidate. The new complex was characterized by infrared spectroscopy (FT-IR), electronic spectra, magnetic susceptibility, electron spin resonance (ESR), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). The anti-diabetic effect of VC was investigated in comparison to vanadium sulfate in streptozotocin (STZ)-induced diabetic rats. Treatment of diabetic rats with VC versus vanadyl sulfate showed a more potent effect on reducing serum glucose and cholesterol close to normal levels. VC suppressed the diabetes-induced upregulation of hepatic glucose transporter (GLUT)-2, Phosphoenol pyruvate carboxykinase (PEPCK), and hormone-sensitive lipase (HSL) more significantly than vanadyl sulfate. Either vanadyl sulfate or VC restored hepatic sterol regulatory element-binding protein transcription factor-1c (SREBP-1c) and muscle hexokinase (HK) mRNA expression that was downregulated in diabetic group. Pyruvate kinase (PK) mRNA expression was restored more significantly in VC-treated than vanadyl sulfate-treated diabetic rats. These results indicate that the newly synthesized VC could be an effective anti-diabetic candidate as the anti-diabetic activity of the ionic vanadium was enhanced after being modified with the organic ligand, thiamin. The results also suggest that VC achieves its effect most likely through modulating the transcription of energy metabolizing enzymes.
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PMID:Synthesis, characterization, and efficacy evaluation of a new anti-diabetic vanadyl(II) thiamine hydrochloride complex in streptozotocin-induced diabetic rats. 2581 95