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 natural product of the glucose-6-phosphate dehydrogenase reaction is 6-phosphoglucono-delta-lactone, which must be hydrolyzed to 6-phosphogluconic acid before it can be further metabolized by 6-phosphogluconate dehydrogenase. Because this lactone is very unstable, it has been uncertain whether the enzyme that hydrolyzes it, 6-phosphogluconolactonase, is required for functioning of the hexose monophosphate pathway. We have purified glucose-6-phosphate dehydrogenase, 6-phosphogluconolactonase, and 6-phosphogluconate dehydrogenase from human erythrocytes to the point where each enzyme is essentially free of each of the other activities. We constructed an artificial hexose monophosphate pathway from these enzymes, providing as substrate 14C-labeled glucose-6-phosphate either directly or by continual generation from 14C-glucose by yeast hexokinase and adenosine triphosphate. The oxidation of 6-phosphogluconic acid was estimated by measuring the CO2 formed. In the absence of a reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-oxidizing system, such as oxidized glutathione (GSSG)-glutathione reductase or phenazine methosulfate, little CO2 was formed, and the presence of 6-phosphogluconolactonase did not affect the amount that was produced. When the hexose monophosphate pathway was stimulated by providing an NADPH-oxidizing system, CO2 was produced two and a half to five times as fast in the presence of 6-phosphogluconolactonase as in its absence. These studies suggest that 6-phosphogluconolactonase is required for the functioning of the hexose monophosphate pathway when the rate of oxidation of NADPH is accelerated.
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PMID:Limiting role of 6-phosphogluconolactonase in erythrocyte hexose monophosphate pathway metabolism. 393 73

Microinjection of frog oocytes allows the modification of intracellular levels of substrates, intermediates, cofactors and enzymes. Use of labeled glucose at specific positions has led us to conclude that oocytes utilize glucose mainly for glycogen synthesis and to a lesser extent for the pentose-P pathway. Glycolysis, glycogenolysis and gluconeogenesis are not operative in these cells. The subject of compartmentation of glucose utilization has been addressed in this paper. First, we show that microinjection of glucose results in a 30-fold increase of carbon incorporation into glycogen when compared to oocytes incubated at saturating glucose concentrations. On the other hand, carbon incorporation into CO2, remains at about the same levels in both conditions Second, microinjection of NADP+ increases CO2 release and inhibits glycogen synthesis from glucose. Third, co-injection of unlabeled intermediates affects differentially glycogen synthesis and CO2 production from labeled glucose. Finally, microinjection of pure yeast hexokinase stimulates markedly 14CO2 release and inhibits glycogen synthesis. We conclude that two separate pools of glucose-6-P exists in oocytes: one pool is committed to the pathway of glycogen synthesis while a second pool serves as substrate for the operation of the pentose-P pathway.
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PMID:Search for compartments of glucose metabolism in the microinjected frog oocyte. 393 91

Some enzyme activities and metabolic features of the black Ma melanotic, brown MI melanotic and Ab amelanotic melanomas of hamster were investigated. The activities of hexokinase and phosphofructokinase were similar in all three melanomas, the activity of NAD-dependent glycerol-3-phosphate dehydrogenase was higher in the amelanotic melanoma and that of pyruvate kinase and lactate dehydrogenase were slightly lower in MI than in the other tumors. The activities of citrate synthase, succinate dehydrogenase and malate dehydrogenase were higher in the Ma and MI melanotic melanomas than in the Ab amelanotic melanoma. The rate of labeled CO2 production from 6-14C-glucose, 1,5-14C-citric acid and U-14C-glutamine was about 2 times higher in melanotic melanomas than in amelanotic one, while no significant differences among the three melanomas were found in respect to 1-14C-glucose and U-14C-glycerol-3-phosphate. The production of 14CO2 was much higher from 1-14C-glucose than from 6-14C-glucose in all the melanomas studied. L-DOPA stimulated the production of 14CO2 from 1-14C-glucose much stronger in the Ma and MI melanomas than in the Ab melanoma. In none of the tumors the incorporation from 6-14C-glucose to CO2 was affected by L-DOPA. It is postulated that oxidation of glucose via the pentose phosphate cycle is involved in melanogenesis.
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PMID:Metabolic characterization of three hamster melanoma variants. 406 92

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

A method is described for the determination of the pH of intracellular water based on the distribution of [14C]benzoate (0.01 mM) between intra- and extra-cellular water. Benzoate at higher concentrations (2-10mM) enters the yeast cell in the undissociated form, and its neutralization within the cell can cause a shift of the pH of the intracellular water by more than 1 pH unit. Benzoate causes an accumulation of the two hexose monophosphates of yeast glucose fermentation and a decrease in intermediates beyond phosphofructokinase, suggesting inhibition at this stage. Benzoate also causes a concomitant fall in [ATP]. Phosphofructokinase is inhibited to a greater extent than hexokinase at acid pH. There is a relationship between intracellular pH, phosphofructokinase inhibition and CO2 production, suggesting that the antifungal action of benzoate is caused by an accumulation of benzoate at low external pH, which lowers the intracellular pH into the range where phosphofructokinase is sensitive. The subsequent inhibition of glycolysis causes a fall in [ATP] and thus restricts growth.
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PMID:Studies on the mechanism of the antifungal action of benzoate. 622 83

In vitro biochemical characteristics of three strains of Haemonchus contortus, benzimidazole-susceptible, mebendazole-resistant and thiabendazole-resistant isolates, were investigated. Steady-state pool sizes of glucose and metabolic intermediates, including adenine nucleotides and end-products revealed no differences between adult worms resistant or susceptible to benzimidazoles in 30-60 min incubations. Possible regulatory steps in the glycolytic pathway are identified as those involving the enzymes hexokinase, phosphofructokinase and pyruvate kinase. The major component of carbohydrate reserves was trehalose, some glycogen was present and the glucose pool was small. On incubation for 18 h in vitro, carbohydrates were metabolised in all three strains. However, in the benzimidazole-susceptible worms there was a preferential use of the glycogen reserves to maintain energy metabolism. All three strains had similar levels of total lipid, total protein and free amino acid and these did not change on incubation. The major products found in the medium on incubation, in vitro, for 18 h were propionate, acetate and propanol, with smaller amounts of ethanol, lactate and malate. All three strains produced a similar sum total of end-products; however, in the mebendazole-resistant strain there appeared to be a diversion of carbon flow to the ethanol-producing pathway. Carbon dioxide production in 60 min incubations was measured using radioactively labelled glucose. A greater output of labelled CO2 was noted under aerobic than anaerobic conditions. This was particularly true of the mebendazole-resistant strain and, in this strain, was sensitive to cyanide. The extent to which metabolic differences noted in the three strains may be related to benzimidazole resistance is not readily apparent.
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PMID:Energy metabolism of adult Haemonchus contortus in vitro: a comparison of benzimidazole-susceptible and -resistant strains. 642 5

The rate of oxidation of glucose is reduced in mouse embryos in the prolonged free living phase associated with delayed implantation and increases when the embryos are reactivated by estrogen. To determine how these changes in metabolism are regulated, several aspects of glucose metabolism were evaluated in dormant and reactivated blastocysts: 1) Embryos were exposed to 14C-pyruvate in vitro and evolved 14CO2 was measured. It was found that the rate of production of CO2 was equal in the two types of blastocysts, suggesting that aerobic pathways are fully functional during delayed implantation. 2) Production of lactate in the presence of O2 was measured and a decrease of 30% was found in delayed implanting embryos, suggesting that the overall regulatory mechanism for glucose metabolism resides in the glycolytic portion of the pathway. 3) Capacity for uptake and phosphorylation of glucose was evaluated using 3H-2-deoxyglucose and was found to be equal in the two types of embryos. 4) Total amounts of the rate-controlling enzymes for glycolysis (i.e., hexokinase and phosphofructokinase) in lysates of delayed and reactivated embryos were found to be equal, indicating that amounts of these enzymes are not limiting in delayed implantation. 5) Lactate production, measured under anaerobic conditions, was found to be equal, demonstrating that it is not the capacity for glycolysis but a difference in the degree of allosteric inhibition that is responsible for reduced glucose oxidation in delayed implantation. 6) Levels of ATP, ADP, and hexose-6-phosphates were found to be consistent with allosteric inhibition of the glycolytic pathway at phosphofructokinase during delay and a release of this inhibition with reactivation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regulation of glycolysis in the mouse blastocyst during delayed implantation. 647 Jun 45

Rat heart mitochondria oxidizing pyruvate (in the presence of 20% as much malate) took up nearly the amount of oxygen required for complete oxidation to CO2. Thus pyruvate, a physiological substrate of the citrate cycle, is oxidized through the entire cycle in these mitochondria, and they seem suitable for study of regulation of integrated mitochondrial energy transduction. By addition of graded amounts of hexokinase or pyruvate kinase to the suspending medium (in the presence of excess glucose or phosphoenolpyruvate), a wide range of steady-state values of the ATP/ADP concentration ratio was obtained. At a constant concentration of phosphate, the steady-state rate of oxygen uptake by rat heart mitochondria oxidizing pyruvate was a function of the adenylate energy charge or of the ATP/ADP ratio, and relatively independent of the absolute concentrations of these nucleotides. The oxygen uptake rates typically spanned a range of about 20-fold. At very high values of the ATP/ADP ratio, the rate of oxygen uptake is much lower than the "state 4" rate seen after added ADP has been phosphorylated. This result suggests that "state 4" respiration, at least in these freshly prepared mitochondria, measures the rate at which ADP is made available by ATPase activity, rather than indicating uncoupling of electron transport from phosphorylation. The concentration of orthophosphate affected the rate of oxygen uptake and the pattern of response to the ATP/ADP ratio or the energy charge, but the effects did not seem interpretable in terms of the mass-action expression for hydrolysis of ATP, (ATP)/ (ADP) (Pi).
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PMID:Adenine nucleotide control of the rate of oxygen uptake by rat heart mitochondria over a 15- to 20-fold range. 671 43

Using the tissue culture technique we have recently demonstrated that long-term exposure of human adipose tissue to human growth hormone (GH) in vitro leads to an impairment in glucose incorporation into triglycerides. This effect was further studied in the present investigation. Biopsies of human adipose tissue which had been cultured for one week with or without GH were studied in subsequent short-term incubations where the conversion of glucose to CO2 and to total lipids was determined. The formation of CO2 was not changed by previous exposure of the biopsies to GH whereas the incorporation of glucose into triglycerides was reduced by about one third. Total glucose metabolism, as determined from the sum of the two pathways, was significantly reduced. The activities of three glycolytic enzymes were determined in biopsies of human adipose tissue which had been cultured with or without GH for one week. The activity of phosphofructokinase was reduced, while the hexokinase and the glucose-6-phosphate dehydrogenase activities were unchanged. The diminished activity of phosphofructokinase, the enzyme considered to be rate-limiting for glycolysis in human fat cells, may be responsible for the decreased rate of glucose metabolism found.
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PMID:Reduced glucose incorporation to triglycerides following chronic exposure of human fat cells to growth hormone. 677 70

1. In vitro glucose uptake and glycogen utilization by Hymenolepis microstoma decreased under high oxygen concentrations. 2. 5-Hydroxytryptamine did not stimulate in vitro glucose uptake but did increase glycogen utilizations by H. microstoma. 3. The reduced glucose uptake under high oxygen concentrations (21 and 95%) resulted in a reduction in excretory products. 4. 14CO2-incorporation studies confirmed that, under both 95% O2:5% CO2 and air-minus-CO2 (identical to 21% O2). CO2-fixation by phosphoenolpyruvate carboxykinase (EC 4.1.1.32) was inhibited. 5. The specific activity of hexokinase (EC 2.7.1.1), phosphofructokinase (EC 2.7.1.11) and pyruvate kinase (EC 2.7.1.40) was not stimulated by 5-HT. 6. The concentration of ATP required for optimal stimulation of phosphofructokinase activity was 0.67 mM. Activity was further significantly increased by the addition of cAMP and even greater by AMP.
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PMID:5-hydroxytryptamine, glucose uptake, glycogen utilization and carbon dioxide fixation in Hymenolepis microstoma (Cestoda). 681 65


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