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)

Current cell disruption and fractionation techniques are time consuming and unsuitable for metabolic studies. We have developed a rapid method for platelets in which separation of cytosol and particle fraction is obtained within 50 s. Isolated platelet suspensions were incubated with low concentrations of digitonin followed by separation of soluble and particle fraction by centrifugation through a phthalate layer. Cell disruption was 90.1+/-4.2% (mean+/-SD, n=18; lactate dehydrogenase leakage). Contamination of granules: acid hydrolase vesicles 16.2+/-3.6% (n=18, beta-N-acetylglucosaminidase), dense granules 7--9% (n=3, 14C-serotonin), mitochondrial matrix 0.6+/-0.1% (n=18, glutamate dehydrogenase). Low concentrations of digitonin did not affect sialic acid content, nucleoside diphosphate kinase and phosphodiesterase activity in isolated membranes. The method showed that most enzymes of glycolysis and hexose monophosphate shunt were localized in the cytosol except for hexokinase (96% particle bound), phosphoglucose isomerase (10% bound) and glutathion reductase (26% bound). About half the total ATP+ADP and most glycolytic intermediates were found partly particle bound, especially fructose 1,6-diphosphate (40% bound). The data suggest that in platelets glycolysis occurs in different cell compartments.
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PMID:Rapid separation of cytosol and particle fraction of human platelets by digitonin-induced cell damage. 737 1

Preliminary studies of 13 enzymes subserving various metabolic pathways were undertaken in tumor-free liver biopsy samples from cancer patients and control subjects. The observations indicate that as a result of nonhepatic neoplasms, with (7 cases) or without (6 cases) hepatic involvement, the biochemical composition of the liver becomes partially undifferentiated. Quantification of appropriate enzymes in histologically normal liver samples could thus distinguish clearly between cancer hosts and controls. The best discriminators include two hepatic enzymes whose concentrations were decreased to less than 30% of normal (soluble glutamate dehydrogenase and the cold stable pyrroline-5-carboxylate reductase) and three for which it was elevated two to four-fold (hexokinase, peptidyl proline hydroxylase and thymidine kinase) in response to distant neoplasms. The same alterations in hepatic enzyme pattern were not seen in any cancer-free patients with or without morphologic liver damage.
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PMID:Enzyme pathology of the liver in patients with and without nonhepatic cancer. 737 35

Galactosamine-induced hepatitis caused a marked increase in plasma lactate and pyruvate, but completely abolished the increase in ketone bodies in the rat exposed to an 8000 m simulated altitude. Plasma free fatty acid as the precursor of ketone bodies was higher in the galactosamine-treated rats during and after an exposure to 8000 m altitude. Treatment of the rat with galactosamine markedly reduced activities of citrate synthase, fumarase, glutamate dehydrogenase and fructose 1,6-bisphosphatase, but increased hexokinase and glucose 6-phosphate dehydrogenase in the liver. The effect of galactosamine-induced hepatitis on the energy metabolism can be explained by a reduction of mitochondrial oxidative enzymes and gluconeogenesis, and involves a shift of the aerobic metabolism to anaerobic glycolysis at high altitude.
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PMID:Effect of galactosamine-induced hepatitis on the aerobic and anaerobic metabolism of the rat exposed to high-altitude hypoxia. 774 7

The aim of the present study is to compare normal and tumoral pancreatic islet cells in terms of both the activity of selected cytosolic and mitochondrial enzymes participating to nutrient catabolism and the intrinsic properties of FAD-glycerophosphate dehydrogenase. The activity of the glycolytic enzymes hexokinase and lactate dehydrogenase was higher in tumoral (RINm5F) than normal islet cells. The opposite was seen for glutamate decarboxylase, glutamate-oxaloacetate transaminase, glutamate-pyruvate transaminase, glutamate dehydrogenase, 2-ketoglutarate dehydrogenase and FAD-glycerophosphate dehydrogenase (m-GDH). These findings are consistent with the high rates of glycolysis and protein synthesis seen in tumoral islet cells compared with normal islet cells, which favour mitochondrial oxidative events associated with the catabolism of D-glucose and amino acids. The intrinsic catalytic properties of m-GDH were comparable, albeit not identical, in normal and tumoral islet cells. Since a deficiency of m-GDH in pancreatic islets may represent a contributing factor in the pathogenesis of non-insulin-dependent diabetes, it is proposed that RINm5F cells may readily yield sufficient islet m-GDH for purification and further gene cloning.
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PMID:Activity of cytosolic and mitochondrial enzymes participating in nutrient catabolism of normal and tumoral islet cells. 776 86

Subcellular localization of hexokinase in the honeybee drone retina was examined following fractionation of cell homogenate using differential centrifugation. Nearly all hexokinase activity was found in the cytosolic fraction, following a similar distribution as the cytosolic enzymatic marker, phosphoglycerate kinase. The distribution of enzymatic markers of mitochondria (succinate dehydrogenase, rotenone-insensitive cytochrome c reductase, and adenylate kinase) indicated that the outer mitochondrial membrane was partly damaged, but their distributions were different from that of hexokinase. The activity of hexokinase in purified suspensions of cells was fivefold higher in glial cells than in photoreceptors. This result is consistent with the hypothesis based on quantitative 2-deoxy[3H]glucose autoradiography that only glial cells phosphorylate significant amounts of glucose to glucose-6-phosphate. The activities of alanine aminotransferase and to a lesser extent of glutamate dehydrogenase were higher in the cytosolic than in the mitochondrial fraction. This important cytosolic activity of glutamate dehydrogenase was consistent with the higher activity found in mitochondria-poor glial cells. In conclusion, this distribution of enzymes is consistent with the model of metabolic interactions between glial and photoreceptor cells in the intact bee retina.
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PMID:Cellular and subcellular localization of hexokinase, glutamate dehydrogenase, and alanine aminotransferase in the honeybee drone retina. 815 42

The maximal rates (Vmax) of some enzyme activities related to synaptosomal energy metabolism were studied in different types of synaptosomes from cerebellar cortex of Macaca Fascicularis (Cynomolgus monkey). Different synaptosomal populations, namely "large" and "small" synaptosomes, were isolated from the anterior lobule of the cerebellar cortex of monkeys treated p.o. with dihydroergocriptine at the dose of 12 mg/kg/day before and during the induction of a Parkinson's-like syndrome by MPTP administration (i.v., 0.3 mg/kg/day for 5 days). The enzymes were chosen according to their regulatory role and as markers of the following metabolic pathways: (a) glycolysis ((hexokinase, phosphofructokinase, lactate dehydrogenase), (b) Krebs' (TCA) cycle (citrate synthase, malate dehydrogenase), (c) amino acid, glutamate metabolism (glutamate dehydrogenase, glutamate-pyruvate- and glutamate-oxaloacetate-transaminases), (d) acetylcholine catabolism (acetylcholinesterase) and (e) ATPases, i.e. Na(+)-K(+)-ATPase, Mg(2+)-ATP synthetase, Mg(2+)-ATPase, Ca(2+)-Mg(2+)-ATPase and Ca(2+)-ATPase Low and High affinity for Ca2+. The MPTP administration modified the activities of citrate synthase, malate dehydrogenase, Na(+)-K(+)-ATPase, acetylcholinesterase and glutamate-oxaloacetate transaminase only on selected types of synaptosomes. Pharmacological treatment by dihydroergocriptine was able to recovery at the steady-state levels the activities of these enzymes, thus demonstrating a partial protective effect on these biochemical parameters.
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PMID:Parkinson-like disease by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity in Macaca fascicularis: synaptosomal metabolism and action of dihydroergocriptine. 817 63

The energy metabolism of a mammalian cell line grown in vitro was analyzed by substrate consumption rates and metabolic flux measurements. The data allowed the determination of the relative importance of the pathways of glucose and glutamine metabolism to the energy requirements of the cell. Changes in the substrate concentrations during culture contributed to the changing catalytic activities of key enzymes, which were determined. 1. A murine B-lymphocyte hybridoma (PQXB1/2) was grown in batch culture to a maximum cell density of 1-2 x 10(6) cells/mL in 3-4 d. The intracellular protein content showed a maximum value during the exponential growth phase of 0.55 mg/10(6) cells. Glutamine was completely depleted, but glucose only partially depleted to 50% of its original concentration when the cells reached a stationary phase following exponential growth. 2. The specific rates of glutamine and glucose utilization varied during culture and showed maximal values at the midexponential phase of 2.4 nmol/min/10(6) cells and 4.3 nmol/min/10(6) cells, respectively. 3. A high proportion of glucose (96%) was metabolized by glycolysis, but only limited amounts by the pentose phosphate pathway (3.3%) and TCA cycle (0.21%). 4. The maximum catalytic activity of hexokinase approximates to the measured flux of glycolysis and is suggested as a rate-limiting step. In the stationary phase, the hexokinase activity reduced to 11% of its original value and may explain the reduced glucose utilization at this stage. 5. The maximal activities of two TCA cycle enzymes were well above the measured metabolic flux and are unlikely to pose regulatory barriers. However, the activity of pyruvate dehydrogenase was undetectable by spectrophotometric assay and explains the low level of flux of glycolytic metabolites into the TCA cycle. 6. A significant proportion of the glutamine (36%) utilized by the cells was completely oxidized to CO2. 7. The measured rate of glutamine transport into the cells approximated to the metabolic flux and is suggested as a rate-limiting step. 8. Glutamine metabolism is likely to occur via glutaminase and amino transaminase, which have significantly higher activities than glutamate dehydrogenase. 9. The calculated potential ATP production suggests that, overall, glutamine is the major contributor of cellular energy. However, at the midexponential phase, the energy contribution from the catabolism of the two substrates was finely balanced--glutamine (55%) and glucose (45%).
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PMID:Glucose and glutamine metabolism of a murine B-lymphocyte hybridoma grown in batch culture. 826 5

The activities of hexokinase isoenzymes, lactate dehydrogenase, cytosolic NAD-linked glycerophosphate dehydrogenase, mitochondrial FAD-linked glycerophosphate dehydrogenase, and glutamate dehydrogenase were measured in homogenates of rat purified pancreatic B and non-B islet cells. In B cell homogenates, the maximal activity of hexokinase and glucokinase was one to two orders of magnitude lower than that of lactate dehydrogenase. The activity of the mitochondrial FAD-linked glycerophosphate dehydrogenase was also much lower than that of the cytosolic NAD-linked glycerophosphate dehydrogenase . A comparable hierarchy in the activity of these enzymes was observed in non-B islet cells. These findings reinforce the view that the preferential stimulation of oxidative glycolysis observed in insulin-producing cells, when exposed to high concentrations of D-glucose, is attributable to a Ca2+-induced activation of the mitochondrial FAD-linked glycerophosphate dehydrogenase, rather than to saturation of the catalytic activity of lactate dehydrogenase.
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PMID:Relevance of lactate dehydrogenase activity to the control of oxidative glycolysis in pancreatic islet B-cells. 861 12

Herbivorous voles, Microtus arvalis, have characteristics similar to herbivores in that their hepatic glycolytic enzyme activities are relatively low. The effects of a single low dose (100 mg/kg body weight) of streptozotocin (STZ) in voles were studied and the difference in sensitivity to or toxicity of STZ in voles and C57BL/6 mice was compared. In voles which received STZ, the cumulative incidence of glycosuria reached 53% by 4 weeks after administration. The diabetic voles showed marked increases in their blood glucose and plasma free fatty acid concentrations and a significant decrease in plasma immunoreactive insulin concentrations. Their hepatic hexokinase, glucokinase, glutathione peroxidase and glutamate dehydrogenase activities decreased significantly and lesions were widely observed in the liver, kidney and pancreas. The activities of glutathione peroxidase, a scavenger of H2O2, decreased significantly in their liver and pancreas. These changes were not observed in C57BL/6 mice which received STZ. The higher sensitivity to and toxicity of STZ in voles than in mice are considered to be caused by the characteristically low activities of glycolytic enzymes and glutathione peroxidase in the tissues of voles. Voles may be a good model for studying the mechanisms of cytotoxicity by STZ in herbivorous animals.
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PMID:High sensitivity to streptozotocin in herbivorous voles, Microtus arvalis, compared to mice. 873 20

Oxidative metabolism in the heart is tightly coupled to mechanical work. Because this coupling process is believed to involve Ca2+, the roles of mitochondrial Ca2+ in the regulation of oxidative phosphorylation was studied in isolated rat heart mitochondria. The electrical component of the mitochondrial membrane potential (delta psi) and the redox state of the pyridine nucleotides were determined during the oxidation of various substrates under different metabolic states. In the absence of added adenine nucleotides, the NADP+ redox couple was almost completely reduced, regardless of the specific substrate and the presence of Ca2+, whereas NAD+ couple redox state was highly dependent on the substrate type and the presence of Ca2+. Titration of respiration with ADP, in the presence of excess hexokinase and glucose, showed that both respiration and NAD(P)+ reduction were very sensitive to ADP. The maximal enzyme reaction rate of ADP-stimulated respiration Michaelis constants (Km) for ADP were dependent on the particular substrate employed. delta psi was much less sensitive to ADP. With either alpha-ketoglutarate or glutamate as substrate, Ca2+ significantly increased reduction of NAD(P)+.Ca2+ did not influence NAD(P)+ reduction with either acetylcarnitine or pyruvate as substrate. In the presence of ADP, delta psi was increased by Ca2+ at all metabolic states with glutamate plus malate, 0.5 mM alpha-ketoglutarate plus malate, or pyruvate plus malate as substrates. The data presented support the hypothesis that cardiac respiration is controlled by the availability of both Ca2+ and ADP to mitochondria. The data indicate that an increase in substrate supply to mitochondria can increase mitochondrial respiration at given level of ADP. This effect can be produced by Ca2+ with substrates such as glutamate, which utilize alpha-ketoglutarate dehydrogenase activity for oxidation. Increases in respiration by Ca2+ may mitigate an increase in ADP during periods of increased cardiac work.
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PMID:Substrate specific effects of calcium on metabolism of rat heart mitochondria. 896 82


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