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)

This study addresses the potential role of skeletal muscle hexokinase (HK) II in the regulation of glucose uptake and metabolism in vivo. Male rats undertook a single bout of treadmill exercise and were then killed immediately or after a predetermined recovery period. Three muscles [soleus (Sol), gastrocnemius/plantaris (Gc), and white vastus] were excised, and HK II mRNA, GLUT-4 mRNA, total HK (HK I and HK II) and heat-stable HK (predominantly HK I) activities were assessed. Three hours after the cessation of a single bout of exhaustive exercise, HK II mRNA was significantly increased in all three muscles. Ninety or thirty minutes of exercise, with a 3-h recovery, increased Gc HK II mRNA to the same extent as exhaustive exercise, but 15 min of exercise had no effect. Gc HK II mRNA continued to increase up to 8 h after the cessation of 90 min of exercise but returned to basal by 24 h postexercise. In contrast to HK II mRNA, Gc GLUT-4 mRNA was unchanged at 0, 3, 8, and 24 h after the cessation of 90 min of exercise. Total HK activity was significantly increased in Sol and Gc, 8 and 24 h after the cessation of 90 min of exercise. Heat-stable HK activity was unchanged in all three muscles. The increase in total HK activity, inferred to be an increase of HK II, may be important in the persistence of the postexercise increase in insulin action.
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PMID:Rat skeletal muscle hexokinase II mRNA and activity are increased by a single bout of acute exercise. 814 Dec 74

Two hexokinases were characterized in Schizosaccharomyces pombe: hexokinase 1, with a low phosphorylation coefficient on glucose (Km 8.5 mM) and hexokinase 2, a kinetically conventional hexokinase. Genes hxk1+ and hxk2+ encoding these enzymes were cloned and sequenced. Disruption of hxk1+ had no effect on growth but disruption of hxk2+ doubled the generation time in glucose. Spores carrying the double disruption hxk1+ hxk2+ did not grow on glucose or fructose after one week. Expression of hxk1+ increased strongly during growth in fructose or glycerol. Expression of hxk2+ was highest during growth in glycerol. A NADP-dependent glucose dehydrogenase was detected, but not a glucokinase.
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PMID:Schizosaccharomyces pombe possesses an unusual and a conventional hexokinase: biochemical and molecular characterization of both hexokinases. 854 30

Defects of glucose transport and phosphorylation may underlie insulin resistance in obesity and non-insulin-dependent diabetes mellitus (NIDDM). To test this hypothesis, dynamic imaging of 18F-2-deoxy-glucose uptake into midthigh muscle was performed using positron emission tomography during basal and insulin-stimulated conditions (40 mU/m2 per min), in eight lean nondiabetic, eight obese nondiabetic, and eight obese subjects with NIDDM. In additional studies, vastus lateralis muscle was obtained by percutaneous biopsy during basal and insulin-stimulated conditions for assay of hexokinase and citrate synthase, and for immunohistochemical labeling of Glut 4. Quantitative confocal laser scanning microscopy was used to ascertain Glut 4 at the sarcolemma as an index of insulin-regulated translocation. In lean individuals, insulin stimulated a 10-fold increase of 2-deoxy-2[18F]fluoro-D-glucose (FDG) clearance into muscle and significant increases in the rate constants for inward transport and phosphorylation of FDG. In obese individuals, the rate constant for inward transport of glucose was not increased by insulin infusion and did not differ from values in NIDDM. Insulin stimulation of the rate constant for glucose phosphorylation was similar in obese and lean subjects but reduced in NIDDM. Insulin increased by nearly twofold the number and area of sites labeling for Glut 4 at the sarcolemma in lean volunteers, but in obese and NIDDM subjects translocation of Glut 4 was attenuated. Activities of skeletal muscle HK I and II were similar in lean, obese and NIDDM subjects. These in vivo and ex vivo assessments indicate that impaired glucose transport plays a key role in insulin resistance of NIDDM and obesity and that an additional impairment of glucose phosphorylation is evident in the insulin resistance of NIDDM.
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PMID:The effect of non-insulin-dependent diabetes mellitus and obesity on glucose transport and phosphorylation in skeletal muscle. 867 80

A single bout of acute exercise increases hexokinase (HK) II mRNA and enzyme activity [R. M. O'Doherty, D. P. Bracy, H. Osawa, D. H. Wasserman, and D. K. Granner. Am. J. Physiol. 266 (Endocrinol. Metab. 29): E171-E178, 1994]. The present study addresses the mechanism of the increase in HK II mRNA. Male rats undertook a single bout of treadmill exercise and were then killed immediately or after a predetermined recovery period. The gastrocnemius/plantaris muscle complex, composed of mixed fiber types, was excised; the nuclei were isolated; and HK I, HK II, beta-actin, and alpha-tubulin gene transcription rates were measured. Genomic DNA and plasmid DNA were used as positive and negative controls, respectively. Immediately after the cessation of 30, 45, or 90 min of exercise, HK II gene transcription rates were 1.3 +/- 0.3-,2.9 +/- 0.3-, and 4.0 +/- 0.6-fold, respectively, above those of sedentary controls. The increases after 45 and 90 min of exercise were statistically significant (P < 0.01). One hour after the cessation of 30 min of exercise, HK II gene transcription was significantly increased (1.40 +/- 0.03-fold; P < 0.05). At all time points, transcription of the HK I, beta-actin, and alpha-tubulin genes was unchanged. We conclude that the exercise-induced increase in HK II gene transcription appears to play a major role in the increase of HK II mRNA and activity.
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PMID:Transcription of the rat skeletal muscle hexokinase II gene is increased by acute exercise. 887 47

A single bout of exercise increases the rate of insulin-stimulated glucose uptake and metabolism in skeletal muscle. Exercise also increases insulin-stimulated glucose 6-phosphate in skeletal muscle, suggesting that exercise increases hexokinase activity. Within 3 h, exercise increases hexokinase II (HK II) mRNA and activity in skeletal muscle from rats. It is not known, however, if a single bout of moderate-intensity exercise increases HK II expression in humans. The present study was undertaken to answer this question. Six subjects had percutaneous biopsies of the vastus lateralis muscle before and 3 h after a single 3-h session of moderate-intensity aerobic (60% of maximal oxygen consumption) exercise. Glycogen synthase, HK I, and HK II activities as well as HK I and HK II mRNA content were determined from the muscle biopsy specimens. The fractional velocity of glycogen synthase was increased by 446 +/- 84% after exercise (P < 0.005). Hexokinase II activity in the soluble fraction of the homogenates increased from 1.2 +/- 0.4 to 4.5 +/- 1.6 pmol.min-1.microgram-1 (P < 0.05) but was unchanged in the particulate fraction (4.3 +/- 1.3 vs. 5.3 +/- 1.5). HK I activity in neither the soluble nor particulate fraction changed after exercise. Relative to a 28S rRNA control signal, HK II mRNA increased from 0.091 +/- 0.02 to 0.195 +/- 0.037 (P < 0.05), whereas HK I mRNA was unchanged (0.414 +/- 0.061 vs. 0.498 +/- 0.134, P < 0.20). The increase in HK II activity after moderate exercise in healthy subjects could be one factor responsible for the enhanced rate of insulin-stimulated glucose uptake seen after exercise.
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PMID:Regulation of hexokinase II activity and expression in human muscle by moderate exercise. 948 62

Hexokinase type I (HK I; ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1), the predominant glucose-phosphorylating enzyme in red blood cells, exists in human erythrocytes in multiple molecular forms that differ in isoelectric point and are separable by ion-exchange chromatography. The major forms, designated HK Ia, Ib and Ic, have similar kinetic properties but are characterized by different age-dependent decay and different intracellular distribution in reticulocytes. HK Ib, which elutes between HK I and HK II in the DEAE ion-exchange chromatography, appears to be unique to RBCs and different from any other hexokinase isozyme previously described. Indeed, Murakami and Piomelli recently reported the presence of a specific HK isozyme (named HKr) expressed in K562 cells and in human reticulocytes and, moreover, the resolution of the human HK I gene structure provided the direct evidence of an erythroid-specific exon 1. To further investigate the microheterogeneity of HK I in human RBCs we established a prokaryotic expression system for the HKr isozyme, using the pET plasmid, inducible with IPTG. The recombinant HKr, expressed in bacterial cells as a catalytically active enzyme, was purified to homogeneity by a combination of DEAE ionexchange chromatography followed by hydrophobic interaction chromatography and dye-ligand affinity chromatography. The kinetic and chromatographic properties of the homogeneous recombinant HKr suggest that this erythroid-specific HK isozyme in fact corresponds to the HK isoform previously described in human RBCs and referred to as HK Ib.
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PMID:Expression, purification, and characterization of a recombinant erythroid-specific hexokinase isozyme. 985 93

Glycolysis is essential for cerebral energy generation. Hence, expression and regulation of gene-encoding brain hexokinase (HK I), the exclusive brain glucose phosphorylating enzyme, can be a critical step in this process. The present study demonstrates the ability of recombinant brain insulin-like growth factor (BIGF, a closely related member of insulin superfamily) to stimulate HK I gene expression in a concentration- and time-dependent manner in C6 glial cells. BIGF treatment (10 ng/ml) on quiescent C6 glial cells stimulates transcription and translation of HK I RNA to approximately 2.5-fold within 4 h after the addition of growth factor. In contrast, insulin or epidermal growth factor could not mimic this effect. Coincubation of cycloheximide with BIGF abolished this stimulatory effect, indicating a requirement for prior protein synthesis for this effect. These results suggest that IGF may have a role in regulating hexokinase gene expression in brain and possibly of brain glucose metabolism.
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PMID:Stimulation of brain hexokinase gene expression by recombinant brain insulin-like growth factor in C6 glial cells. 988 33

Potato (Solanum tuberosum L.) plants transformed with sense and antisense constructs of a cDNA encoding the potato hexokinase 1 (StHK1) exhibited altered enzyme activities and expression of StHK1 mRNA. Measurements of the maximum catalytic activity of hexokinase revealed a 22-fold variation in leaves (from 22% of the wild-type activity in antisense transformants to 485% activity in sense transformants) and a 7-fold variation in developing tubers (from 32% of the wild-type activity in antisense transformants to 222% activity in sense transformants). Despite the wide range of hexokinase activities, no change was found in the fresh weight yield, starch, sugar, or metabolite levels of transgenic tubers. However, there was a 3-fold increase in the starch content of leaves from the antisense transformants after the dark period. Starch accumulation at the end of the night period was correlated with a 2-fold increase of glucose and a decrease of sucrose content. These results provide strong support for the hypothesis that glucose is a primary product of transitory starch degradation and is the sugar that is exported to the cytosol at night to support sucrose biosynthesis.
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PMID:Antisense repression of hexokinase 1 leads to an overaccumulation of starch in leaves of transgenic potato plants but not to significant changes in tuber carbohydrate metabolism. 1048 67

We analyzed the structural features of insulin-potentiating fragments of human growth hormone by computative simulations. The peptides were designated from the N-terminus sequences of the hormone positions at 1-15 (hGH(1-15); H2N-Phe1-Pro2-Thr3-Ile4-Pro5-Leu6-Ser7-Arg8-L eu9-Phe10-Asp11-Asn12-Ala13-Met14-Leu15 -COOH), 6-13 (hGH(6-13)), 7-13 (hGH(7-13)) and 8-13 (hGH(8-13)), which enhanced insulin-producing hypoglycemia. In these peptide molecules, ionic bonds were predicted to form between 8th-arginyl residue and 11th-aspartic residue, and this intramolecular interaction caused the formation of a macrocyclic structure containing a tetrapeptide Arg8-Leu9-Phe10-Asp11. The peptide positions at 6-10 (hGH(6-10)), 9-13 (hGH(9-13)) and 10-13 (hGH(10-13)) did not lead to a macrocyclic formation in the molecules, and had no effect on the insulin action. Although beta-Ala13hGH(1-15), in which the 13th-alanine was replaced by a beta-alanyl residue, had no effect on insulin-producing hypoglycemia, the macrocyclic region (Arg8-Leu9-Phe10-Asp11) was observed by the computative simulation. An isothermal vibration analysis of both of beta-Ala13hGH(1-15) and hGH(1-15) peptide suggested that beta-Ala13hGH(1-15) is molecule was more flexible than hGH(1-15); C-terminal carboxyl group of Leu15 easily accessed to Arg8 and inhibited the ionic bond formation between Arg8 and Asp11 in beta-Ala13hGH(1-15). The peptide of hGH(8-13) dose-dependently enhanced the insulin-involved fatty acid synthesis in rat white adipocytes, and stabilized the C6-NBD-PC (1-acyl-2-[6-[(7-nitro-2,1,3benzoxadiazol-4-yl)amino]-caproyl]-sn- glycero-3-phosphatidylcholine) model membranes. In contrast, hGH(9-13) had no effect both on the fatty acid synthesis and the membrane stability. In the same culture conditions as the fatty acid synthesis assay, hGH(8-13) had no effect on the transcript levels of glucose transporter isoforms (GLUT 1, 4) and hexokinase isozymes (HK I, II) in rat white adipocytes. Judging from these results we considered that the macrocyclic structure in human growth hormonal peptides is regarded with the modification of insulin action, and hGH(8-13) is an essential sequence for the modification of insulin action. This hGH(8-13) peptide modifies the insulin action via stabilizing the cell membrane, and does not directly act on the insulin-involved glucose metabolism.
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PMID:Analyses of insulin-potentiating fragments of human growth hormone by computative simulation; essential unit for insulin-involved biological responses. 1097 21

Quantitative imaging of glucose metabolism of human brain tumors with PET utilizes 2-[(18)F]-fluorodeoxy-D-glucose (FDG) and a conversion factor called the lumped constant (LC), which relates the metabolic rate of FDG to glucose. Since tumors have greater uptake of FDG than would be predicted by the metabolism of native glucose, the characteristic of tumors that governs the uptake of FDG must be part of the LC. The LC is chiefly determined by the phosphorylation ratio (PR), which is comprised of the kinetic parameters (Km and Vmax) of hexokinase (HK) for glucose as well as for FDG (LC proportional to (Km(glc) x Vmax(FDG))/(Km(FDG) x Vmax(glc)). The value of the LC has been estimated from imaging studies, but not validated in vitro from HK kinetic parameters. In this study we measured the kinetic constants of bovine and 36B-10 rat glioma HK I (predominant in normal brain) and 36B-10 glioma HK II (increased in brain tumors) for the hexose substrates glucose, 2-deoxy-D-glucose (2DG) and FDG. Our principal results show that the KmGlc < KmFDG << Km2DG and that PR2DG < PRFDG. The FDG LC calculated from our kinetic parameters for normal brain, possessing predominantly HK I, would be higher than the normal brain LC predicted from animal studies using 2DG or human PET studies using FDG or 2DG. These results also suggest that a shift from HK I to HK II, which has been observed to increase in brain tumors, would have little effect on the value of the tumor LC.
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PMID:Kinetic characterization of hexokinase isoenzymes from glioma cells: implications for FDG imaging of human brain tumors. 1129 20


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