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

The effects of exogenously administered 3',5'-monophosphate (cyclic AMP) on glycogen synthesis and hexose monophosphate shunt enzymes were studied in the uteri of immature and ovariectomized rats to determine whether cyclic AMP mimics the known effects of estrogenic hormones. The injection of cyclic AMP concurrently with theophylline, significantly increased the activity of uterine hexokinase, phosphofructokinase, pyruvate kinase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, and uterine glycogen content in immature rats (p less than .05). These increases were related to the dose of cyclic AMP, and as little as .2 mg was able to stimulate uterine glycogen to 169% of control values. The treatment did not significantly increase the activity of the key glycolytic or hexose monophosphate shunt enzymes in the lung and thymus, although these tissues are also not receptive to estrogen. Neither estradiol-17beta or cyclic AMP and theophylline produced any measurable effect on the uterine enzymes, isocitrate dehydrogenase, or alpha-glycerophosphate dehydrogenase. In ovariectomized and adrenalectomized-ovariectomized animals, cyclic AMP and theophylline significantly stimulated the activity of key glycolytic and hexose monophosphate shunt enzymes (p less than .05); the N6, 02-dibutyryl analog of cyclic AMP being more potent than the parent compound. Pretreatment with actinomycin or cycloheximide significantly inhibited the effects of cyclic AMP and theophylline (p less than .05), which indicates that neither cyclic AMP stimulation or the inhibition of the effects of cyclic AMP were dependent on adrenal function. The results support the possiblity that cyclic AMP may be involved in mediating the metabolic effects of estrogen on the uterus.
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PMID:Metabolic control mechanisms in mammalian systems. XV. Studies on the role of adenosine 3' ,5'-monophosphate in estrogen action on the uterus. 411 Aug 9

Redistribution of axonal enzymes as a function of time in vitro was studied in an unbranched segment of frog sciatic nerve. Cholinesterase activity moved peripherally at a rate of 99 mm/day and centrally at 19 mm/day. One-quarter of the total nerve content of the enzyme was estimated to be in motion, one-eighth in each direction. Mitochondrial enzymes (hexokinase and glutamic dehydrogenase) moved peripherally at 20-31 mm/day, centrally at 11-20 mm/day. Only 10% of the total content of these mitochondrial enzymes was in motion. No movement of choline acetylase or 6-phosphogluconic dehydrogenase activity was seen even after 4 days in vitro. However, in a 12 day in vivo experiment choline acetylase moved toward the periphery at a rate of 0.34 mm/day. After a day or so in vitro the distal accumulations of cholinesterase and glutamic dehydrogenase decreased, with a concomitant and quantitatively equivalent increase in enzyme activities at the proximal end of the nerve. It is postulated that during incubation a mechanism for reversing the direction of flow develops in the peripheral stump of the nerve. Vinblastine inhibited central and peripheral flow of both cholinesterase and glutamic dehydrogenase. Movement of cholinesterase was not affected by ouabain, thalidomide, or phenobarbital, nor by K(+) excess (110 mM) or absence.
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PMID:Transport of axonal enzymes in surviving segments of frog sciatic nerve. 411 99

1. Superovulated rat ovary slices from rats treated with 20mug. of luteininzing hormone/100g. body wt. 2hr. before death and from control animals have been incubated in vitro. Output of Delta(4)-3-oxo steroids (0.2mumole/g. wet wt./hr. in control tissue) was linear for 4hr., and was increased by approx. 70% in slices from luteinizing hormone-treated rats. Rate of oxygen consumption (90.0+/-4.6mumoles/g. wet wt./hr.) was linear for 3hr. and unaltered by luteinizing hormone treatment or addition of glucose (1mg./ml.) to the medium. 2. In slices from control animals, steady-state rate of glucose uptake was 78.0+/-2.9mug. atoms of carbon/g. wet wt./hr.; steady-state rates of lactate output, pyruvate output and incorporation of [U-(14)C]-glucose carbon atoms into carbon dioxide and total lipid extract were 60.7+/-0.9, 2.4+/-0.1, 18.0+/-1.1 and 0.7+/-0.1mug. atom of carbon/g. wet wt./hr. and accounted for 104.5+/-1.9% of the glucose uptake. In slices from luteinizing hormone-treated rats, glucose uptake and outputs of lactate, pyruvate and [(14)C]carbon dioxide were increased by approx. 25%, and 108.4+/-3.2% of the glucose uptake could be accounted for. 3. The total lipid extract was separated by thin-layer chromatography and saponification. Of the (14)C incorporated into this fraction during incubation with [U-(14)C]glucose 97% was found in the fractions containing glyceride glycerol and less than 3% in the fractions containing sterols, steroids or fatty acids. Appreciable quantities of (14)C were incorporated into these lipid fractions from [1-(14)C]acetate. 4. From a consideration of the tissue glycogen content, the specific activities of [(14)C]lactate and glucose 6-phosphate (C-1) derived from [1-(14)C]-, [6-(14)C]- and [U-(14)C]-glucose, and the ratio of [(14)C]carbon dioxide yields from [1-(14)C]glucose and [6-(14)C]glucose, it was concluded that there was no appreciable glycogenolysis or flow through the pentose phosphate cycle. 5. In ovary slices from both control and luteinizing hormone-treated animals, glucose in vitro raised the incorporation rate of (14)C from [1-(14)C]acetate into sterols and steroids. Luteinizing hormone in vivo stimulated the incorporation rate in vitro but only in the presence of glucose. 6. In slices incubated in medium containing [(3)H]water, [(14)C]sorbitol and glucose (1mg./ml.), the total water space (865+/-7.1mul./g.) and the extracellular water space (581+/-22mul./g.) were unchanged by luteinizing hormone treatment in vivo but the glucose space was raised from 540+/-23.6mul./g. to 639+/-31.3mul./g. 7. Luteinizing hormone treatment was found to lower the tissue concentration of the hexose monophosphates and to increase the total activity of hexokinase, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase and possibly of phosphofructokinase. 8. The kinetic properties of a partially purified preparation of phosphofructokinase were found to be qualitatively similar to those from other mammalian tissues. 9. The results are discussed with reference to both the role of glucose metabolism in steroidogenesis and the mechanism by which luteinizing hormone increases the rate of glucose uptake.
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PMID:Glucose metabolism in the superovulated rat ovary in vitro. Effects of luteinizing hormone and the role of glucose metabolism in steroidogenesis. 424 Jul 7

Previous studies have shown a marked effect of very high levels of copper on red cell glucose-6-phosphate dehydrogenase and glutathione. When the effect of more nearly physiological levels of copper were studied, red cell hexokinase, phosphofructokinase, phosphoglyceric kinase, pyruvate kinase, and 6-phosphogluconate dehydrogenase were found to be inhibited. Inhibition was observed both when copper was added directly to hemolysates or when hemolysates were prepared from red cells from whole blood which had been incubated with copper and washed. The inhibition of red cell enzymes by copper was completely reversed by the addition of EDTA.
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PMID:The effect of copper on red cell enzyme activities. 425 5

1. Lactic acid formation in supernatant fractions of homogenates of cat or rat small-intestinal mucosa was measured under optimum conditions with glucose, fructose, glucose 6-phosphate, fructose 1,6-diphosphate or 3-phosphoglycerate as substrate. 2. Between 80 and 107% of the glycolytic activity of the homogenate was recovered in these particle-free preparations when glucose, fructose, glucose 6-phosphate or fructose 1,6-diphosphate was used as substrate. 3. Evidence was obtained that hexokinase and phosphofructokinase were the rate-limiting enzymes in the initial sequence of glycolytic reactions. The limitation of rate by hexokinase was much more pronounced in preparations from the cat than in those from the rat. 4. With subcellular preparations from cat or rat small intestine lactic acid was also formed from ribose 5-phosphate and at rates similar to those observed with glucose. 5. A higher rate of glycolysis was observed with glucose 6-phosphate as substrate with preparations from the proximal half of the small intestine of the rat as compared with the distal half. 6. Mucosal preparations from rats starved for 24-48hr. exhibited only about one-quarter of the glycolytic activity of those of fed control groups. The decreased rate of formation of lactic acid from either glucose or fructose was mainly due to a decrease in the activity of hexokinase(s). The activities of glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase and a number of other enzymes were not significantly decreased by starvation. 7. The results are discussed in relation to metabolic control of glycolysis in other mammalian tissues.
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PMID:Glucose metabolism in the mucosa of the small intestine. Glycolysis in subcellular preparations from the cat and rat. 429 Sep 84

1. Assessment of the overall metabolic changes in lactating mammary gland after thyroidectomy has been made by measurement of the incorporation of (14)C from specifically labelled glucose, pyruvate and acetate into (14)CO(2) and (14)C-labelled lipid in the experimental rats and in sham-operated control animals. 2. Thyroidectomy depressed the oxidation of (14)C-labelled substrates, an effect still apparent when the control rats were pair-fed with thyroidectomized rats; however, the ratio of oxidation of [1-(14)C]glucose/oxidation of [6-(14)C]glucose was unaltered. In parallel with these studies it was revealed that the activities of hexokinase, glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and NADP-linked isocitrate dehydrogenase were all lower in the thyroidectomized group than in the pair-fed control group. 3. Thyroidectomy also lowered the incorporation of (14)C-labelled substrates into (14)C-labelled lipid, an effect further studied by measurement of the activities of citrate-cleavage enzyme and acetate thiokinase. Restricting the food intake of the control rats to that of the thyroidectomized group lowered the activity of citrate-cleavage enzyme, but no further depression was observed on thyroidectomy. The oxidized and reduced nicotinamide nucleotide content of mammary tissue was shown to be decreased in the thyroidectomized rats compared with the control rats.
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PMID:Effect of thyroidectomy on pathways of glucose metabolism in lactating rat mammary gland. 438 95

1. The degradation rates and half-lives of hexokinase, 6-phosphogluconate dehydrogenase, lactate dehydrogenase, pyruvate kinase, glucose 6-phosphate dehydrogenase, phosphoglycerate kinase and aldolase were calculated from measurements of the decline in activities of these enzymes in rat small intestine during starvation. 2. The half-lives of the enzymes are: hexokinase, 5.7h; 6-phosphogluconate dehydrogenase, 7.6h; glucose 6-phosphate dehydrogenase, 6.0h; pyruvate kinase, 8.9h; lactate dehydrogenase, 8.7h; phosphoglycerate kinase, 8.7h; aldolase, 5.1h. 3. The significance of the results is discussed with respect to the regulation of enzyme concentrations in response to changes in diet.
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PMID:Degradation of glucose-metabolizing enzymes in the rat small intestine during starvation. 472 2

1. The pentose phosphate pathway in Krebs ascites cells was investigated for regulatory reactions. For comparison, the glycolytic pathway was studied simultaneously. 2. Activities of the pentose phosphate pathway enzymes were low in contrast with those of the enzymes of glycolysis. The K(m) values of glucose 6-phosphate dehydrogenase for both substrate and cofactor were about four times the reported upper limit for the enzyme from normal tissues. Fructose 1,6-diphosphate and NADPH competitively inhibited 6-phosphogluconate dehydrogenase. 3. About 28% of the hexokinase activity was in the particulate fraction of the cells. The soluble enzyme was inhibited by fructose 1,6-diphosphate and ribose 5-phosphate, but not by 3-phosphoglycerate. The behaviour of the partially purified soluble enzyme in vitro in a system simulating the concentrations of ATP, glucose 6-phosphate and P(i) found in vivo is reported. 4. Kinetics of metabolite accumulation during the transient state after the addition of glucose to the cells indicated two phases of glucose phosphorylation, an initial rapid phase followed abruptly by a slow phase extending into the steady state. 5. Of the pentose phosphate pathway intermediates, accumulation of 6-phosphogluconate, sedoheptulose 7-phosphate and fructose 6-phosphate paralleled the accumulation of glucose 6-phosphate. Erythrose 4-phosphate reached the steady-state concentration by 2min., whereas the pentose phosphates accumulated linearly. 6. The mass-action ratios of the pentose phosphate pathway reactions were calculated. The transketolase reaction was at equilibrium by 30sec. and then progressively shifted away from equilibrium towards the steady-state ratio. The glucose 6-phosphate dehydrogenase was far from equilibrium at all times. 7. Investigation of the flux of [(14)C]glucose carbon confirmed the existence of an operative pentose phosphate pathway in ascites cells, contributing 1% of the total flux in control cells and 10% in cells treated with phenazine methosulphate. 8. The pentose phosphate formed by way of the direct oxidative route and estimated from the (14)CO(2) yields represented 20% of the total accumulated pentose phosphate, the other 80% being formed by the non-oxidative reactions of the pentose phosphate pathway. 9. The pentose phosphate pathway appears to function as two separate pathways, both operating towards pentose phosphate formation. Control of the two pathways is discussed.
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PMID:The pentose phosphate pathway of glucose metabolism. Enzyme profiles and transient and steady-state content of intermediates of alternative pathways of glucose metabolism in Krebs ascites cells. 536 Jun 73

1. Erythrocytes from normal and glucose 6-phosphate dehydrogenase-deficient humans were subjected to hydrogen peroxide diffusion to oxidize the GSH. Studies were carried out in the presence and absence of chromate to inhibit glutathione reductase and with or without the addition of glucose. 2. The GSH content of erythrocytes from other species was oxidized by subjecting them to hydrogen peroxide diffusion in the presence of chromate and glucose. 3. Chromate (1.3mm) inhibited glutathione reductase by about 80%, whereas glucose 6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, hexokinase, phosphofructokinase and pyruvate kinase were not inhibited. 4. The GSSG formed was transported from the erythrocytes to the medium. 5. The transport rate of GSSG from glucose 6-phosphate dehydrogenase-deficient erythrocytes subjected to hydrogen peroxide diffusion in the presence of chromate was comparable with that from normal and glucose 6-phosphate dehydrogenase-deficient erythrocytes. 6. The rate of transport of GSSG from erythrocytes of various species studied could be ranked: pigeon>rabbit>rat>donkey>man>dog>horse>sheep>chicken>fish.
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PMID:The transport of oxidized glutathione from the erythrocytes of various species in the presence of chromate. 538 75


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