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)

1. The following were measured in pieces of perirenal adipose tissue obtained from foetal lambs at about 120 days of gestation or within 3 days of term, and 9-month-old sheep: the rates of synthesis from glucose of fatty acids, acylglycerol glycerol, pyruvate and lactate; the rate of glucose oxidation to CO2 and the proportions contributed by the pentose phosphate cycle, pyruvate dehydrogenase and the tricarboxylic acid cycle; the activities of hexokinase, glucose 6-phosphate dehydrogenase, phosphofructokinase, pyruvate kinase and pyruvate dehydrogenase. 2. The total rate of glucose utilization was lower in pieces of adipose tissue from near-term lambs than 120-day foetal lambs and the pattern of glucose metabolism differed, with, for example, a much smaller proportion of glucose carbon being used for fatty acid synthesis, whereas a greater proportion of glucose oxidation occurred via the tricarboxylic acid cycle in the near-term lambs. In general, these differences in glucose metabolism were not associated with differences in the activities of the various enzymes listed above. 3. The rates of glucose utilization per fat-cell by 120-day foetal lambs and 9-month-old sheep were very similar but, again, the proportions metabolized to the various products differed. In particular, there was a smaller proportion of glucose oxidized via the pentose phosphate cycle and a greater proportion oxidized via pyruvate dehydrogenase and the tricarboxylic acid cycle in adipose tissue from foetal lambs. These differences were matched by a lower activity of glucose 6-phosphate dehydrogenase and a higher pyruvate dehydrogenase activity in fat-cells from the foetal lambs.
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PMID:Glucose metabolism and its regulation in pieces of perirenal adipose tissue from foetal lambs. 687 Aug 2

Construction and fit to experimental data of a computer model of glycolysis, the tricarboxylic acid cycle, and related metabolism in the perfused rat heart involving 63 enzyme submodels is described. The experimental preparation simulated is a rat heart perfused with Krebs bicarbonate solution containing glucose and insulin whose pH was lowered to 6.6 by equilibration with 35% CO2-65% O2. The glycolytic rate falls sharply and ischemia results, becoming apparent after 3.5 min. The model initially ascribes the fall in glycolysis largely to inhibition of hexokinase by accumulated glucose 6-phosphate and inactivation of phosphofructokinase by the low pH and subsequently to cytoplasmic glucose depletion owing to limitation of glucose uptake by the external acidosis. At the same time there is insufficiently deep hypoxia to trigger substantial mobilization of endogenous fuels (e.g., glycogenolysis or fatty acid mobilization, so that these hearts become ischemic primarily owing to a shortage of metabolic fuel.
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PMID:Computer simulation of energy metabolism in acidotic cardiac ischemia. 708 79

Isolated ovine adipocytes were incubated in vitro with specifically labeled 14C-glucose in the presence or absence of acetate. The flux patterns of glucose carbon through major metabolic pathways were estimated. When glucose was added as the sole substrate, approximately equal portions of glucose carbon (10%) were oxidized to CO2 in the pentose phosphate pathway, in the pyruvate dehydrogenase reaction and in the citrate cycle. Fifteen percent of the glucose carbon was incorporated into fatty acids and 43% was released as lactate and pyruvate. Addition of acetate to the medium increased glucose carbon uptake by 1.5-fold. Most of this increase was accounted for by a sevenfold increase in the activity of the pentose phosphate pathway. Acetate increased glucose carbon fluxes via pentose phosphate pathway to triose phosphates, from triose phosphate to pyruvate, into glyceride glycerol, into lactate and pyruvate and into pyruvate dehydrogenase and citrate cycle CO2. Glucose carbon incorporated into fatty acids was decreased 50% by acetate while, carbon fluxes through the phosphofructokinase-aldolase reactions were not significantly increased. Results of this study suggest that, when glucose is the sole substrate, the conversion of glucose to fatty acids in ovine adipocytes may not be limited by the maximum capacity of hexokinase, the pentose phosphate pathway or enzymes involved in the conversion of triose phosphates to pyruvate and of pyruvate to fatty acid. Acetate increased glucose utilization apparently by increasing activity of the pentose phosphate pathway as a result of enhanced NADPH utilization for fatty acid synthesis.
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PMID:Glucose metabolism and effect of acetate in ovine adipocytes. 714 48

The purpose of the present study was to document the metabolism of glucose and its responsiveness to insulin in isolated pancreatic acini from rats fed either a low- or high-fat diet. The different steps investigated were labeled glucose oxidation, lactate production, hexokinase activity, and glucose transport, which was assessed by using both 3-O-methylglucose and 2-deoxyglucose. The acinar capacity to metabolize glucose (sum of CO2 plus lactate) was decreased by 50% by feeding the rats a high-fat diet. The impairment of glucose metabolism could not be explained by a defect in the glucose phosphorylation step because hexokinase activity was not changed in isolated acini from rats fed a high-fat diet. The effect of a high-fat diet was entirely accounted for by a reduction in the glucose transport rate that was achieved through a decrease in glucose transport Vmax with no change in Km. We could not detect any effect of insulin on glucose metabolism or 2-deoxyglucose uptake, whatever the diet composition. This work establishes that a high-fat diet, known to markedly alter pancreatic exocrine enzymes, also induces a large decrease in acinar glycolytic flux, raising the question of the relation between these two sets of adaptive changes.
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PMID:Effects of high-fat diet on glucose metabolism in isolated pancreatic acini of rats. 714 28

We review the development of our knowledge and interpretations of the intermediary metabolism of Trypanosoma (Schizotrypanum) cruzi. Already in the 1950's it was clearly established that when this organism was exposed to large external concentrations of carbohydrates it was unable to catabolize them completely, even in the presence of oxygen, producing a mixture of CO2, dicarboxylic acids (succinic, malic) and alanine as end products. However, subsequent work tended to emphasize such paradigmatic features as a full complement of glycolytic enzymes in all stages of the life cycle of the parasite, a functional Kreb's cycle, a cytochrome-dependent electron transport chain and phosphorylative oxidation which suggested that T. cruzi had the basic metabolic properties of classical glucose-utilizing cells, in contrast with the degenerate glycolytic metabolism of bloodstream African trypanosomes. Only in the 1980's interest revived on the how and why of the incomplete carbohydrate catabolism by this parasite. The primary reason for this anomaly was found to be the presence of a constitutive phospho-enol-pyruvate carboxykinase (PEPCK, ATP-dependent, E.C.4.1.1.49), present in all stages of the parasite's life cycle, and the lack of regulation of the glycolytic route at its classical control points, hexokinase and phosphofructokinase. On the other hand, the presence of two distinct glutamate dehydrogenases (NAD+ and NADP(+)-dependent), the former being strictly regulated by the energy charge of the cell and the Krebs' cycle activity, indicated that amino acids can be a primary source of energy for this organism.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The limitations of paradigms: studies on the intermediary metabolism of Trypanosoma cruzi. 767 May 50

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 human leukaemic cell line HL60 undergoes differentiation to granulocyte-like cells in response to dimethylsulphoxide (DMSO). The rates of glucose and glutamine utilization were studied in HL60 cells that were either undifferentiated or fully differentiated by 9 days exposure to DMSO. Differentiation did not alter the rate of utilization of exogenous glucose, approximately 75% of which was converted to lactate in each case. The activities of hexokinase, phosphofructokinase, pyruvate kinase and citrate synthase were similarly unaffected. In contrast, the activity of the oxidative segment of the pentose-phosphate pathway was enhanced by differentiation, and no glycogen synthase activity could be detected. These observations are consistent with the significantly lower content of glycogen, the increased activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase and the increased oxidation of [1-14C] glucose relative to [6-14C] glucose in the differentiated cells. Glucose utilization was depressed by exogenous glutamine but, at the same time, glutamine utilization was enhanced by glucose in both cell types; these reciprocal effects were more pronounced in the undifferentiated HL60 cells. Glucose utilization may be depressed in the presence of glutamine as a result of the allosteric inhibition of a rate-limiting step of glycolysis (eg. phosphofructokinase). In spite of having glutaminase activity twice that of their differentiated counterparts, the uptake of glutamine by undifferentiated HL60 cells was low, especially when it was the sole substrate. The stimulation of glutaminolysis by glucose may be due to activation of mitochondrial glutamine transport. A large proportion of the glutamine utilized by both cells contributed to a net accumulation of glutamate, aspartate and alanine, whilst up to 35% was oxidized to CO2. In contrast, almost all of the glucose utilized was converted to lactate and very little was oxidized. The high rates of glycolysis and glutaminolysis observed before and after differentiation may not contribute primarily to energy production but may supply, in undifferentiated cells, substrates for biosynthetic processes that generate nucleic acid precursors or, in the case of differentiated cells which synthesize reactive oxygen intermediates, substrates that maintain NADP in a reduced state.
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PMID:Glycolytic, glutaminolytic and pentose-phosphate pathways in promyelocytic HL60 and DMSO-differentiated HL60 cells. 833 14

The effect of lonidamine on glucose metabolism, hexokinase activity and adenylate pool of MCF-7 human breast cancer cells sensitive and resistant to adriamycin has been investigated. The following summarizes the results: 1. In both cell types the greatest part of glucose was metabolized to lactate, whereas only a small proportion of glucose carbon atoms was incorporated into CO2, lipids, nucleic acids, and supporting structures. 2. Glucose utilization, lactate production, and ATP content were higher in resistant cells due to a greater activity of mitochondrial hexokinase. 3. Lonidamine decreased glucose utilization, aerobic glycolysis and ATP content in both cell types and the effect was significantly higher on resistant cells. 4. The extent of inhibition in sensitive and resistant cells overlapped that found for mitochondrially bound hexokinase, thus indicating that the greater sensitivity of resistant cells to lonidamine was due to their higher amount of bound hexokinase. These findings confirmed a modified glucose metabolism in cells with resistant phenotype and suggested that lonidamine might be usefully used to reduce or overcome multidrug resistance of those cells with a reduced ability to accumulate and retain antitumor drugs.
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PMID:Effect of the antitumor drug lonidamine on glucose metabolism of adriamycin-sensitive and -resistant human breast cancer cells. 882 7

After frozen storage for 7 d, the viability and CO2 productivity of a conventional baker's yeast strain D greatly decreased. The viability of a freeze-tolerant strain, DFT, used for the frozen dough method slightly decreased after the same storage period, while the CO2 productivity greatly decreased. The CO2 productivity and DNase I inhibitory activity of actin of the cell-free extracts prepared immediately after thawing from 7-d frozen-stored cells markedly decreased in both strains. In DFT, however, the productivity and the inhibitory activity of the cell-free extract increased when the extract was prepared after incubation of the frozen-thawed cells at 30 degrees C. The increase in the inhibitory activity first occurred and then the increase in the CO2 productivity. Gel filtration patterns of actin and glycolytic enzymes were compared between cell-free extracts of both strains. Peaks of actin and activity peaks of hexokinase and pyruvate kinase decreased in the strain D after frozen storage, but only slightly in the strain DFT. After frozen storage, phosphofructokinase activity peak shifted to a lower molecular weight in strain D.
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PMID:Impairment of the glycolytic system and actin in baker's yeast during frozen storage. 882 26

Evidence is presented that intermediates of the oxidative pentose phosphate pathway (OPPP) are channeled from one pathway enzyme to the next. CO2 produced from [1-14C]glucose in the presence of unlabelled pathway intermediates contained much more radioactivity than predicted by a model in which pathway-produced intermediates are in equilibrium with identical molecules in the bulk phase. This was the case whether glucose 6-phosphate (Glc6P), 6-phosphogluconolactone, or 6-phosphogluconate was added. Assumptions involved in calculating the amount of 14CO2 predicted for free mixing of 14C-labelled and unlabelled intermediates are discussed, together with the following results. (a) 14CO2 production by pea nodules in the presence of 3 mM 6-phosphogluconate was higher than in its absence. (b) Apparent channeling of intermediates was much higher for purified yeast enzymes than for yeast extract. (c) 6-Phosphogluconate and 6-phosphogluconolactone were channeled between yeast Glc6P dehydrogenase and 6-phosphogluconate dehydrogenase despite the absence of 6-phosphogluconolactonase in the purified yeast enzyme mixture. (d) When purified yeast hexokinase was physically separated from Glc6P dehydrogenase and 6-phosphogluconate dehydrogenase by a dialysis membrane, there was no apparent channeling. (e) Poly(ethylene glycol), high salt and detergents had little effect on apparent channeling of OPPP intermediates, which is consistent with a stable complex of enzymes. On the other hand, density gradient centrifugation experiments suggested a more transient interaction between the enzymes. Taken together, the results support channeling of OPPP pathway intermediates.
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PMID:Evidence for channeling of intermediates in the oxidative pentose phosphate pathway by soybean and pea nodule extracts, yeast extracts, and purified yeast enzymes. 920 16


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