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)

Enzyme activities have been measured in needle biopsies from kidneys of pigs fed 1 ppm or 0.2 ppm of ochratoxin A for 1-5 wks. After feeding 1 ppm toxin for 1 wk, the activity of cytosolic phosphoenolpyruvate carboxykinase (PEPCK) was decreased by 40% and remained inhibited until the termination of the experiment (5 wk). The activity of gamma-glutamyl transpeptidase, a brush-border enzyme found in the proximal tubules, was reduced to a similar degree and remained inhibited. The activities of hexokinase, a cytosolic enzyme of general distribution in the nephron, and phosphate-dependent glutaminase, a distal tubule enzyme, were not affected. The biopsy results were confirmed by measurements in renal slices taken at the termination of the experiment, except that biopsy samples showed more variation in enzyme activity and a lower PEPCK activity. A guinea pig antibody against the cytosolic form of PEPCK was used to demonstrate that the mitochondrial form of the enzyme, which accounts for a considerable part of the total cellular activity, was not affected by ochratoxin A. When mitochondrial PEPCK activity present in the cytosolic fraction was accounted for, ochratoxin A was found to reduce PEPCK activity by 70-80%. The increase of ochratoxin A exposure from zero through 0.2 ppm to 1 ppm, which resulted in dose-dependent activity decrease of PEPCK and gamma-glutamyl transpeptidase, was accompanied by dose-dependent decrease of renal function, as measured by a reduction of maximal tubular excretion of para-aminohippurate per clearance of inulin (TmPAH/CIn) and an increase in glucose excretion. This suggest that these enzymes are sensitive indicators of ochratoxin A-induced porcine nephropathy. Assuming that porcine nephropathy represents a valid model of endemic (Balkan) nephropathy in humans, the measurement of cytosolic PEPCK and gamma-glutamyl transpeptidase activity in the kidney could be a sensitive test for ochratoxin A-induced disease in humans.
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PMID:Renal enzyme activities in experimental ochratoxin A-induced porcine nephropathy: diagnostic potential of phosphoenolpyruvate carboxykinase and gamma-glutamyl transpeptidase activity. 289 56

Aldose reductase is a rate limiting enzyme in the polyol pathway associated with the conversion of glucose to sorbitol. The enzyme is located in the eye (cornea, retina, lens), kidney, myelin sheath, and also in other tissues less involved in diabetic complications. Experiments in diabetic animals have implicated sorbitol accumulation in the lens to the development of cataracts. The use of inhibitors of aldose reductase in animal studies has demonstrated that diabetic complications such as cataracts, nephropathy, and slowing of nerve conduction can be ameliorated. While an osmotic effect can explain the physical changes in the lens leading to cataract formation, the effect of sorbitol accumulation in other tissues and the resulting diabetic complications has been linked to the depletion of myoinositol content resulting in a derangement of sodium-potassium adenosine triphosphatase activity. Since glucose and other hexoses are poor substrates for aldose reductase, it is only in hyperglycemia when the enzyme hexokinase is saturated that aldose reductase is activated, leading to accumulation of sorbitol. The kinetics of inhibition of aldose reductase by a variety of inhibitors has been delineated. The dose required varies from inhibitor to inhibitor and is consistent with their inhibition constants. Toxicity is a consideration in the use of some of the inhibitors, as was demonstrated with sorbinil which caused hypersensitivity reactions in 10 percent of patients. Other inhibitors such as tolerant have shown efficacy and are under clinical investigation. Interpretation of results obtained with aldose reductase inhibitor therapy in human subjects suggest that these inhibitors are effective at early stages of diabetic complications.
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PMID:Aldose reductase and its inhibition in the control of diabetic complications. 845 42

Since type 1 diabetes mellitus (T1DM) patients with nephropathy (DN+) are insulin-resistant, we aimed to identify (new) potential molecular sites involved in the alterations of glucose metabolism in these patients. We examined the expression of glycolytic enzymes in cultured fibroblasts from T1DM(DN+) patients as compared to those from T1DM patients without nephropathy (DN-) and from controls. Pyruvate kinase (PK) activity was also determined. Human skin fibroblasts were grown in normal glucose (6 mM). RNAs and proteins were analyzed, respectively, using cRNA microarray and two-dimensional electrophoresis followed by identification with mass spectrometry. PK activity was measured using a spectrophotometric assay. As compared to controls, increases in the gene expression of hexokinase, phosphoglucomutase, phosphofructokinase, aldolase and triosephosphate isomerase were found in T1DM(DN+) patients, but not in T1DM(DN-) patients. In T1DM(DN+) patients, the protein analysis showed an altered expression of three glycolytic enzymes: triosophosphate isomerase, enolase and PK. In addition, PK activity in fibroblasts from T1DM(DN+) patients was lower than that in T1DM(DN-) and in controls. In conclusion, this study reports novel alterations of enzymes involved in glucose metabolism that may be associated with the pathophysiology of insulin resistance and of renal damage in T1DM(DN+) patients.
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PMID:Glycolytic enzyme expression and pyruvate kinase activity in cultured fibroblasts from type 1 diabetic patients with and without nephropathy. 1884 May 20

Gentamicin (GM) is an effective aminoglycoside antibiotic against severe infections but nephrotoxicity and oxidative damage limits its long term clinical use. Various strategies were attempted to ameliorate GM nephropathy but were not found suitable for clinical practice. Green tea (GT) polyphenols have shown strong chemopreventive and chemotherapeutic effects against various pathologies. We hypothesized that GT prevents GM nephrotoxicity by virtue of its antioxidative properties. A nephrotoxic dose of GM was co-administered to control and GT-fed male Wistar rats. Serum parameters and enzymes of oxidative stress, brush border membrane (BBM), and carbohydrate metabolism were analyzed. GM increased serum creatinine, cholesterol, blood urea nitrogen (BUN), lipid peroxidation (LPO) and suppressed superoxide dismutase (SOD) and catalase activities in renal tissues. Activity of hexokinase, lactate dehydrogenase increased whereas malate dehydrogenase decreased. Gluconeogenic enzymes and glucose-6-phosphate dehydrogenase were differentially altered in the cortex and medulla. However, GT given to GM rats reduced nephrotoxicity parameters, enhanced antioxidant defense and energy metabolism. The activity of BBM enzymes and transport of Pi declined by GM whereas GT enhanced BBM enzymes and Pi transport. In conclusion, green tea ameliorates GM elicited nephrotoxicity and oxidative damage by improving antioxidant defense, tissue integrity and energy metabolism.
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PMID:Protective effect of green tea extract on gentamicin-induced nephrotoxicity and oxidative damage in rat kidney. 1942 67

High salt induced renal disease is a condition resulting from the interactions of genetic and dietary factors causing multiple complications. To understand the metabolic alterations associated with renal disease, we comprehensively analyzed the metabonomic changes induced by high salt intake in Dahl salt-sensitive (SS) rats using GC-MS technology and biochemical analyses. Physiological features, serum chemistry, and histopathological data were obtained as complementary information. Our results showed that high salt (HS) intake for 16 weeks caused significant metabolic alterations in both the renal medulla and cortex involving a variety pathways involved in the metabolism of organic acids, amino acids, fatty acids, and purines. In addition, HS enhanced glycolysis (hexokinase, phosphofructokinase and pyruvate kinase) and amino acid metabolism and suppressed the TCA (citrate synthase and aconitase) cycle. Finally, HS intake caused up-regulation of the pentose phosphate pathway (glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase), the ratio of NADPH/NADP+, NADPH oxidase activity and ROS production, suggesting that increased oxidative stress was associated with an altered PPP pathway. The metabolic pathways identified may serve as potential targets for the treatment of renal damage. Our findings provide comprehensive biochemical details about the metabolic responses to a high salt diet, which may contribute to the understanding of renal disease and salt-induced hypertension in SS rats.
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PMID:High salt diet induces metabolic alterations in multiple biological processes of Dahl salt-sensitive rats. 2956 33