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)

Therapy with enzyme inducing drugs may improve glycemic control in patients with non-insulin-dependent diabetes mellitus. We evaluated the role of a mixed function oxidase system on glucose metabolism with an animal model. Rats were treated with an inducer (phenobarbital), an inhibitor (cimetidine) and a hepatotoxin (carbon tetrachloride) for a week to cause alterations in the liver. The mixed function oxidase system was assayed by determination of the cytochrome P-450 content and NADPH cytochrome c reductase in liver. Carbohydrate metabolism was evaluated by determining blood glucose, enzymes associated with glucose phosphorylation in the liver (glucokinase, hexokinase), glucose storage as glycogen and enzymatic delivery, glucose-6-phosphatase, and peripheral tissue by determining phosphorylating enzyme (hexokinase) and a key glycolytic enzyme (pyruvate kinase) and glycogen content in muscles. The therapy with the inducer enhanced glucose utilization in liver and storage in muscles. The inhibitor decreased the mixed function oxidase system, reduced glucose phosphorylating, but not gluconeogenetic enzymes, in the liver and increased glycolysis in muscles. Carbon tetrachloride, a hepatotoxin, impaired mixed function oxidase, glucose phosphorylating and delivering enzyme activity in liver, reduced blood glucose and caused glycogen accumulation in muscles. The function of liver microsomal enzyme system seems to be closely related to enzymatic glucose metabolism in the liver and muscles.
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PMID:Hepatic mixed function oxidase system and enzymatic glucose metabolism in rats. 304 Mar 22

Data have been obtained suggesting that the complex porin-hexokinase of brain mitochondria may be related to the contact sites between the outer and inner membrane. In the attempt to isolate from brain mitochondria the inner and outer membranes and the boundary membrane contacts, a procedure was developed based on swelling and shrinking of the organelles, followed by sonication and reverse discontinuous density gradient centrifugation. Three fractions were obtained by this technique, which were identified by measuring the relative specific activities of marker enzymes, namely succinate-cytochrome c reductase; NADH-cytochrome c reductase (rotenone insensitive); hexokinase and glutathione transferase, for the inner and outer membranes and contact sites, respectively. The fraction which contains the contact sites is characterized by the highest specific activity of hexokinase and glutathione transferase and by the highest calcium binding capacity; physiological concentrations of this cation produces a sharper separation of this fraction. Results indicate that both the porin-hexokinase gating system of the outer membrane and the calcium transporting complex of the inner membrane are present in the fraction which contains the contact sites.
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PMID:Influence of Ca2+ on the isolation from rat brain mitochondria of a fraction enriched of boundary membrane contact sites. 319 26

The effect of hypoxia and post-hypoxic recovery were studied in gastrocnemius muscle of young-adult and mature beagle dogs. Furthermore, the possible interference of pharmacological treatment with nicergoline was evaluated in these conditions. Muscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose 6-phosphate, pyruvate, lactate), Kreb's cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate) and related free amino acids (glutamate, alanine), ammonium ion, energy store and mediators (ATP, ADP, AMP and creatine phosphate), and the energy charge potential were evaluated. Furthermore, in the crude extract and/or mitochondrial fraction of another portion of the same gastrocnemius muscle the maximum rate (Vmax) of some muscular enzymes related to the anaerobic glycolytic pathway (hexokinase, lactate dehydrogenase), the Kreb's cycle (citrate synthase, malate dehydrogenase), the aminoacid pool related to the Krebs' cycle (glutamate dehydrogenase and aspartate aminotransferase), the electron transfer chain (cytochrome oxidase) and NAD+/NADH exchanges (total NADH cytochrome c reductase) was evaluated. Some glycolytic metabolites and Krebs' cycle intermediates were modified by acute hypoxia, while free amino acids and energy mediators remained practically unchanged. The pharmacological treatment maintained the glucose and succinate muscular concentrations within the normal range, during hypoxia. The behaviour of muscular metabolites during hypoxia and/or post-hypoxic recovery is an age-related event. In fact, only in young-adult animals did the altered values return to normal in post-hypoxic recovery. In the present experimental conditions, only minor changes were observed as far as muscular enzyme activities are concerned. In any case, some enzyme activities tested showed different Vmax in young-adult dogs in comparison with mature ones.
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PMID:Effect of hypoxia, aging and pharmacological treatment on muscular metabolites and enzyme activities. 322 9

Muscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose-6-phosphate, pyruvate, lactate), Krebs cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate), related free amino acids (glutamate, alanine), ammonia, energy store (creatine phosphate), energy mediators (ATP, ADP, AMP) and energy charge potential were evaluated. Furthermore the maximum rate (Vmax) of the following muscular enzyme activities was evaluated in the crude extract and/or mitochondrial fraction: for the anaerobic glycolytic pathway: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; for the tricarboxylic acid cycle: citrate synthase, malate dehydrogenase; for the electron transfer chain: total NADH cytochrome c reductase, cytochrome oxidase. The rat gastrocnemius muscles were analyzed in normoxia and after repeated, alternate hypoxic and normoxic exposures (12 hours of hypoxia daily; for 5 days). Naftidrofuryl was administered daily at three different doses: 10, 15 and 22.5 mg/kg i.m., 30 min before the beginning of the experimental hypoxia. The biochemical adaptation to intermittent normobaric hypoxic-normoxic exposures was characterized by the decrease of the muscular contents of creatine phosphate, citrate, alpha-ketoglutarate and glutamate. This adaptation occurred in absence of significant changes in the Vmax of the muscle enzymes tested. By naftidrofuryl treatment, in gastrocnemius muscle from hypoxic rats both alpha-ketoglutarate and creatine phosphate contents maintained normal values, while glutamate concentration remained reduced to subnormal values. With the exception of hexokinase, naftidrofuryl treatment did not modify the Vmax of marker enzymes related to energy transduction.
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PMID:Adaptation of skeletal muscle energy metabolism to repeated hypoxic-normoxic exposures and drug treatment. 401 59

Muscular glycolytic fuels, intermediates and end-products (glycogen, glucose, glucose-6-phosphate, pyruvate, lactate), Krebs cycle intermediates (citrate, alpha-ketoglutarate, succinate, malate), related free amino acids (glutamate, alanine), ammonia, energy store (creatine phosphate), energy mediators (ATP, ADP, AMP) and energy charge potential were evaluated. Furthermore the maximum rate (Vmax) of the following enzyme activities was evaluated in the crude extract and/or mitochondrial fraction: for the anaerobic glycolytic pathway: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; for the tricarboxylic acid cycle: citrate synthase, malate dehydrogenase; for the electron transfer chain: total NADH cytochrome c reductase, cytochrome oxidase. The rat gastrocnemius muscles were analysed in normoxia and after normobaric intermittent hypoxia (12 hours continuously daily; for 5 days). Cytidine and/or uridine were administered daily at the dose of 120 mg/kg, i.p., 30 min before the beginning of the experimental hypoxia. The intermittent normobaric hypoxia induced a biochemical adaptation characterized by the decrease of the muscular contents of creatine phosphate, citrate, alpha-ketoglutarate and glutamate. This adaptation occurred in the absence of significant changes in the Vmax of the tested muscle enzymes. In gastrocnemius muscle from hypoxic rats, the two biological pyrimidines tested induced various discrete, but often related, modifications of the contents of some Krebs cycle intermediates (i.e., alpha-ketoglutarate, malate) and related free amino acids (i.e., glutamate, alanine). In any case, the treatment with cytidine and/or uridine did not modify the Vmax of marker enzymes related to energy transduction.
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PMID:Modification of the skeletal muscle energy metabolism induced by intermittent normobaric hypoxia and treatment with biological pyrimidines. 402 89

The antifungal antibiotic flavensomycin inhibited the oxidation of amino acids and of glucose by Penicillium oxalicum. The compound inhibited l-amino acid oxidase (EC 1.4.3.2) activity for l-leucine and l-phenylalanine, and also d-amino acid oxidase (EC 1.4.3.3) in the oxidation for dl-alanine. The addition of flavin adenine dinucleotide, which is a cofactor for this enzyme, antagonized the action of the antibiotic. Glucose oxidase (EC 1.1.3.4) was also inhibited. The antibiotic inhibited the reduced nicotinamide adenine dinucleotide (NADH(2)) cytochrome c reductase (EC 1.6.2.1) as well as the much slower nonenzymatic reduction of this cytochrome by the nucleotide. Reduced cytochrome c was also oxidized nonenzymatically by flavensomycin. The antibiotic completely inhibited the action of rabbit muscle lactic dehydrogenase (EC 1.1.1.27) in promoting the reduction of pyruvate by NADH(2) but only slightly affected the reverse reaction. Alcohol dehydrogenase (EC 1.1.1.1) was also similarly inhibited. Flavensomycin prevented the reduction of nicotinamide adenine dinucleotide phosphate by isocitrate in the presence of isocitrate dehydrogenase (EC 1.1.1.42). The hexokinase (EC 2.7.1.1)-catalyzed phosphorylation of glucose, in which the adenosine triphosphate acts as a phosphate donor, was only slightly affected. Flavensomycin also inhibited the action of yeast lactate dehydrogenase (EC 1.1.2.3) on the reduction of cytochrome c. High concentrations of cytochrome c were antagonistic to this reaction. The results point to an interference with enzymatically controlled hydrogen or electron transfer as the mechanism of the antifungal activity of flavensomycin.
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PMID:Flavensomycin, an inhibitor of enzyme reactions involving hydrogen transfer. 438 33

Cells of the aerotolerant anaerobe Giardia lamblia respire in the presence of oxygen. Endogenous respiration is stimulated by glucose but not by other carbohydrates and Krebs cycle intermediates. Endogenous and glucose-stimulated respiration are insensitive to cyanide, malonate, and 2,4-dinitrophenol, but are inhibited by atabrin and iodoacetamide. G. lamblia produces ethanol, acetate and CO2 both aerobically and anaerobically either from endogenous reserves or exogenous glucose. Molecular hydrogen is not produced. The following enzyme activities were detected in homogenates: hexokinase, fructose-biphosphate aldolase, pyruvate kinase, phosphoenolpyruvate carboxykinase, malate dehydrogenase, malate dehydrogenase (decarboxylating), pyruvate synthase, acetyl-CoA synthetase, alcohol dehydrogenase (NADP+), NADH dehydrogenase, NADPH dehydrogenase, NADPH oxidoreductase and superoxide dismutase. The enzymes of energy and carbohydrate metabolism are nonsedimentable (109 000 x g for 30 min). Activities of lactate dehydrogenase, hydrogenase, phosphate acetyltransferase, acetate kinase, citrate synthase, succinate dehydrogenase, fumarate hydratase and catalase were below the limits of detection. The results suggest the occurrence of glycolysis, energy production by substrate level phosphorylation and a flavin, iron-sulfur protein mediated electron transport system as well as the absence of cytochrome mediated oxidative phosphorylation and functional Krebs cycle.
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PMID:Energy metabolism of the anaerobic protozoon Giardia lamblia. 610 7

The effect of tris-(2-chloroethyl)-amine (HN-3) on RNA and DNA was investigated spectrophotometrically. The shift in the absorbance spectrum caused by the addition of HN-3 was used to test a variety of compounds for their ability to inhibit RNA alkylation. The effect of HN-3 on the activity of several enzymes was also investigated. The activities of ribonuclease A, desoxyribonuclease I, acetylcholinesterase, diaphorase, glutathione reductase, adenosine desaminase, glyoxalase I, 3-hydroxyacyl-CoA-dehydrogenase, xanthine oxidase, glucose-6-phosphate dehydrogenase, hexokinase and the microsomal N-oxygenation of aniline were not changed by HN-3, whereas the activity of cytochrome-c-reductase exhibited a dose dependent diminution in the presence HN-3. Of 105 compounds tested only 14, namely, sodium thiosulfate, dithioxanthine, thiosalicylic acid, 1,2,4-triazole-5-thiol, 2-thiocytosine, 2-thiohistadine, 2,3-dithiosuccinic acid, thioglycolic acid, 3-mercapto-D-valine,6-amino-2-thiouracil, thionicotine amide, dithiothreitol, sodium sulfite, and ergothioneine prevented the alkylation of RNA. All of them also reacted with HN-3 in absence of RNA. No correlation was found between the reaction constant of the reaction compound:HN-3 in the absence of RNA and the concentration of the compound which inhibited RNA alkylation by 50%. The compounds which were effective in vitro were also tested in mice for their ability to reduce HN-3 toxicity in vivo. Only sodium thiosulfate, d-penicillamine, and dithiosuccinic acid were effective. A 3.9fold increase in the LD50 of HN-3 was achieved in mice treated with sodium thiosulfate 3330 mg/kg i.p., a 1.7fold with 2125 mg dithiosuccinic acid/kg, and a 2fold increase with 2500 mg/kg d-penicillamine. The compound tested was injected i.p. 0.5 to 1 min after the s.c. injection of HN-3.
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PMID:Effect of various compounds on the reaction of tris-(2-chloroethyl)amine with ribonucleic acid in vitro and on its toxicity in mice. 617 33

(1) Biopsies from the gastrocnemius muscle of patients with Duchenne dystrophy were partitioned into a myofibrillar plus nuclear fraction, a mitochondrial fraction and a supernatant fraction. The fractions were assayed for mitochondrial enzymes and protein, in order to obtain information about the integrity of mitochondrial structure and function. Muscles from boys and adults without neuromuscular disease were treated likewise. (2) In adults, muscle possesses a significantly higher specific activity (on protein basis) of monoamine oxidase and rotenone-insenitive NADH-cytochrome c reductase (RINCR) than in boys. In childhood, monoamine oxidase activity increases with age. At the age of 5 yr, the specific activity is 50% of the adult value. RINCR activity is constant in childhood. With adolescence it increases from 20 +/- 2 (SEM) to 35 +/- 6 mumoles cytochrome c reduced per min per g protein, and it remains at this level. Palmitoyl-CoA synthetase activity remains constant with age. (3) In Duchenne dystrophy the extractable protein content from muscle is decreased to 75%. The specific activities of the matrix enzymes propionyl-CoA carboxylase and glutamate dehydrogenase are 1.8 and 2.8 times increased, the inner membrane enzyme cytochrome c oxidase is 2.8 times increased, the inner membrane enzyme cytochrome c oxidase is 2.8 times increased. Of the outer membrane enzymes RINCR is 2.0 times increased, while palmitoyl-CoA synthetase is not changed in acitivity. In Duchenne dystrophy monoamine oxidase activity also increases with age. In part this may be due to mitochondria from adipose tissue and macrophages, which are increasingly present in older patients. The specific activities of enzymes with a predominant cytosolic localisation, creatine kinase and adenylate kinase, are increased by a factor of 1.5 and 1.7. (4) The subcellular distribution of the studied enzymes in human skeletal muscle was found to be similar as in animal studies. In mitochondrial fractions from Duchenne patients the recoveries of the following enzymes are decreased: glutamate dehydrogenase (from 25 to 9%), creatine kinase (1.1-0.66%), adenylate kinase (0.44-0.22%), hexokinase (7.1-2.7%), monoamine oxidase (36-21%), RINCR (30-17%), and palmitoyl-CoA synthetase (40-21%). The recoveries of last 3 mitochondrial outer membrane enzymes in the supernatant fractions are correspondingly increased. These results indicate an increased fragility of the mitochondrial membranes in dystrophic muscles. (5) The reported changes are clearly evident in a one-year-old patient, which indicates that the mitochondria are involved early in the disease process.
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PMID:Early changes of muscle mitochondria in Duchenne dystrophy. Partition and activity of mitochondrial enzymes in fractionated muscle of unaffected boys and adults and patients. 624 85

We have extended the method of active-enzyme chromatography to include the use of broad zones of enzyme. This allows examination of interacting systems in a way formally analogous to sedimentation velocity so that simulation of the observed activity profiles is possible. The method has been applied using pyridine nucleotide-linked active enzyme assays. At the concentrations presently accessible by this technique, hexokinase and glucose-6-phosphate dehydrogenase, both associating systems, show single symmetrical boundaries, as does isolated diaphorase, while pyruvate and alpha-ketoglutarate dehydrogenases show more complex patterns, with the position of the reaction boundary for diaphorase activity being dependent on enzyme concentration.
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PMID:Broad-zone active-enzyme chromatography. Keto-acid dehydrogenases as associating systems. 668 56


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