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)

The metabolic effects on rat cardiac and skeletal muscle of a strenous program of swimming, of cold acclimation and of isoprenaline treatment (0.3 mg/kg daily for 5 five-day weeks) were compared. Exercised and cold-exposed rats gained less body weight than did controls or isoprenaline-treated rats. In all treated groups the heart and the intercapular brown adipose tissue hypertrophied. The size of the adrenals increased only in isoprenaline-treated animals. Cold-acclimation and physical training increased and isoprenaline treatment reduced or did not affect the activities of succinate dehydrogenase, malate dehydrogenase and citrate synthase of cardiac muscle. In the skeletal muscle all treatments resulted in increased activities of these enzymes. Of the anaerobic enzymes analysed, only the activity of hexokinase increased in response to the treatements used. This increase was the same in cardiac as in skeletal muscle, but it was significantly greater with isoprenaline-treatment than with training or with cold-acclimation. The activities of lactate dehydrogenase and phosphofructokinase did not differ significantly. All treatments improved cold resistance, but only swimming exercise and cold acclimation significantly increased tolerance to exercise. It is concluded that prolonged stimulation of adrenergic beta-receptors by catecholamines is responsible for the metabolic changes observed.
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PMID:Comparison of the effects of physical exercise, cold acclimation and repeated injections of isoprenaline on rat muscle enzymes. 12 87

1. Female Wistar rats were randomly assigned to control (C) or exercising (T) groups and subsequently portioned into 1, 3, 5 and 10 day T and C groups. The T groups completed a progressive endurance running program. Biochemical indices of adaptation were measured in cardiac muscle and in plantaris and soleus muscles of C and T animals after their last exercise bout. 2. In cardiac muscle, myofibrillar ATPase activity was significantly elevated in the 3T (0.241 +/- 0.031) and 5T (0.242 +/- 0.013) groups (P less than or equal to 0.05) compared to their respective controls (3C = 0.187 +/- 0.015 and 5C = 0.190 +/- 0.007). 3. After 10 days of training cardiac myofibrillar ATPase activity was elevated by 17% but this was not significant (P greater than or equal to 0.05). 4. No changes in myofibrillar ATPase activity were seen in skeletal muscle (P greater than or equal to 0.05), however, hexokinase activity progressively increased and was significantly elevated in the 3T, 5T and 10T soleus and plantaris muscles of rats over controls (P less than or equal to 0.05). 5. Minimal nonsignificant changes were noted in the hexokinase activity of the hearts of all T groups (P greater than or equal to 0.05). 6. These results indicate that metabolic adaptation of the heart and skeletal muscles takes place after as little as three training sessions. 7. Although the adaptation of the skeletal muscles continually progresses, the adaptation of the heart appears to be transitory.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biochemical adaptation of cardiac and skeletal muscle to physical activity. 182 40

Hexokinase (EC 2.7.1.1) catalyzes the first step in glucose metabolism, using ATP for the phosphorylation of glucose to glucose 6-phosphate. A portion of the HK1 gene was cloned by mixed oligonucleotide primer amplification of cDNA using primers of high complexity. The amino acid sequence for a partial fragment of bovine cardiac muscle HK was determined and used to create primer mixtures of 256- and 1024-fold complexity. Two products were generated from bovine cardiac muscle cDNA which show 82% nucleotide and 93% amino acid identity with a region of rat brain HK1 and cDNA. This work demonstrates that extension and amplification of cDNA probes may be successful even when amino acid sequence data indicate substantial codon degeneracy.
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PMID:Synthesis and characterization of a bovine hexokinase 1 cDNA probe by mixed oligonucleotide primed amplification of cDNA using high complexity primer mixtures. 271 57

Phosphoglycerate kinase deficiency is a rate, X-linked disorder associated with a severe haemolytic anaemia. In general the deficiency has been demonstrated only in erythrocytes and leucocytes. However, in a subject with this condition, the activity of phosphoglycerate kinase in lymphocytes and platelets was also shown to be less than 5% of the normal value. Following the death of this subject in 1979, the deficiency was also found to occur in tissue samples of brain, skeletal muscle, liver and cardiac muscle, obtained at the autopsy. Values for phosphoglycerate kinase were of the order of 0.5-5% of normal controls. Other glycolytic enzymes which were tested were hexokinase, pyruvate kinase, enolase and 2-phosphoglyceromutase. In general, values for these enzymes were either normal or slightly raised.
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PMID:Tissue levels of glycolytic enzymes in phosphoglycerate kinase deficiency. 625 1

The effect of endurance training on the oxidative and glycolytic potentials of the diaphragm and intercostal muscles of rats has been studied. Training consisted of treadmill running (28 m/min, 60 min/day, 5 days/wk) for periods ranging from 8-26 weeks. Exercise of similar duration and intensity produced a glycogen depletion in the diaphragm and intercostal muscles of nontrained rats. Oxidative potential was estimated from the activity of the mitochondrial marker enzyme succinate dehydrogenase (SDH). The activities of phosphorylase (PHOS), hexokinase (HK), and lactate dehydrogenase (LDH) were determined as well as the distribution of the LDH isozymes. SDH activity averaged 44 (42-51) and 17 (10-22)% (P less than 0.0l) greater in the plantaris and diaphragm muscles, respectively, after 8-12 weeks of endurance running as compared to the sedentary animals. There was no change in the SDH activity of the intercostal muscles or in the activities of the glycolytic enzymes. There was also no change in the distribution of the isozymes of LDH. Extending the duration of the training program to 26 weeks did not produce any additional alteration in the magnitude of the adaptation observed after the initial training period. Comparative studies of different types of muscles demonstrated that the diaphragm, although having a fiber composition somewhat similar to that of a fast-twitch skeletal muscle, has a metabolic profile that is intermediate between pure slow twitch skeletal muscle and cardiac muscle.
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PMID:Response of ventilatory muscles of the rat to endurance training. 707 Sep 57

To investigate whether the energy derived from glycolysis is functionally coupled to Ca2+ active transport in sarcoplasmic reticulum (SR), we determined whether glycolytic enzymes were associated with SR membranes and whether metabolism through these enzymes was capable of supporting 45Ca transport. Sealed right-side-out SR vesicles were isolated by step sucrose gradient from rabbit skeletal and cardiac muscle. Intravesicular 45Ca transport was measured after the addition of glycolytic substrates and cofactors specific for each of the glycolytic reactions being studied or after the addition of exogenous ATP and was expressed as transport sensitive to the specific Ca(2+)-ATPase inhibitor thapsigargin. We found that the entire chain of glycolytic enzymes from aldolase onward, including aldolase, GAPDH, phosphoglycerate kinase (PGK), phosphoglyceromutase, enolase, and pyruvate kinase (PK), was associated with SR vesicles from both cardiac and skeletal muscle. Iodoacetic acid, an inhibitor of GAPDH, eliminated 45Ca transport supported by fructose-1,6-diphosphate, the substrate for aldolase, but transport was completely restored by phosphoenolpyruvate (the substrate for PK), indicating that both of the ATP-producing glycolytic enzymes, GAPDH/PGK and PK, were associated with the SR and functionally capable of providing ATP for the Ca2+ pump. Addition of a soluble hexokinase ATP trap eliminated 45Ca transport fueled by exogenous ATP but had markedly less effect on 45Ca transport supported by endogenously produced ATP (via glycolysis). Similarly, at very low concentrations of ATP and ADP (10 to 50 nmol/L), ATP that was produced endogenously from ADP and phosphoenolpyruvate supported 15-fold more 45Ca transport than ATP that was supplied exogenously at the same concentration. These results are consistent with functional coupling of glycolytic ATP to Ca2+ transport and support the hypothesis that ATP generated by SR-associated glycolytic enzymes may play an important role in cellular Ca2+ homeostasis by driving the SR Ca2+ pump.
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PMID:Functional coupling between glycolysis and sarcoplasmic reticulum Ca2+ transport. 778 86

The glucose transporter GLUT1 may play a more important role in cardiac than in skeletal muscle, but its regulation is unclear. During fasting, cardiac GLUT1 declines in the presence of low plasma insulin and glucose and high nonesterified fatty acid (NEFA) levels, whereas GLUT4 is unchanged. We investigated insulin, glucose, and NEFA levels as regulatory factors of cardiac GLUT content in chronically cannulated rats. Fasting rats were infused for 24 h with saline or insulin (2 rates) while plasma glucose was equalized by a glucose clamp; final transporter content was compared with a fed control group. There was a close association of GLUT1 content with insulin (r2 = 0.83, P < 0.001), with GLUT1 varying over a threefold range, under equivalent fasting glycemic conditions (plasma glucose, 5.1 +/- 0.1 mM). Maintenance of fed insulin levels during fasting prevented the GLUT1 fall (P < 0.01), whereas hyperinsulinemia (117 +/- 10 mU/l) led to significant overexpression of GLUT1 (155 +/- 12% of control, P < 0.01). When high glucose (7.6 +/- 0.1 mM) or high NEFA (0.76 +/- 0.05 mM) levels accompanied the hyperinsulinemia, upregulation of GLUT1 was blocked. GLUT1 content correlated with an estimate of cardiac glucose clearance across the groups. Cardiac GLUT4 content, hexokinase, and acyl-CoA synthase activities were unaffected by fasting, insulin, or substrate manipulation. In conclusion, insulin preferentially upregulates GLUT1 (but not GLUT4) in a dose-dependent manner in cardiac muscle in vivo, and substrate supply modulates this response, since upregulation can be effectively blocked by increased glucose or lipid availability. Therefore, both insulin exposure and energy status of cardiac muscle may be important determinants of cardiac GLUT1 expression.
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PMID:Selective chronic regulation of GLUT1 and GLUT4 content by insulin, glucose, and lipid in rat cardiac muscle in vivo. 932 20

We investigated the effects of anoxia and contractile activity on glucose uptake and the intracellular location of hexokinase in cardiac muscle of the American eel Anguilla rostrata. Uptake of 2-deoxyglucose (2-DG) by ventricle strips at 15 &deg;C was increased by 45 % by anoxia and by 85 % by contractile activity over basal conditions. The anoxia- and contraction-induced increase in basal 2-DG uptake was inhibited completely by 25 &micro;mol l-1 cytochalasin B, suggesting that facilitated glucose transporters are involved. Maximal activity of hexokinase in whole homogenates (approximately 10 &micro;mol min-1 g-1 tissue) was 200 times higher than the maximal rate of 2-DG uptake measured in vitro (46 nmol min-1 g-1 tissue). Only 20&shy;25 % of hexokinase activity was localized to the mitochondrial fraction, and this was not altered by perfusion of the hearts with anoxic media. It is therefore unlikely that anoxia-induced stimulation of 2-DG uptake is mediated by intracellular translocation of hexokinase. As in the case of mammalian muscle, glucose 6-phosphate is a potent inhibitor of hexokinase in eel cardiac muscle (IC50=0.44 mmol l-1). In summary, anoxia and contractile activity significantly increase 2-DG uptake in cardiac muscle of American eels, and glucose transport may be rate-limiting for glucose utilization. Increased utilization of glucose during anoxia or contractile activity may involve the recruitment of facilitative glucose transport proteins to the cell surface of myocytes or an increase in the intrinsic activity of glucose transporters already residing at the cell surface.
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PMID:Acute regulation of glucose uptake in cardiac muscle of the American eel Anguilla rostrata. 934 75

Uteroplacental insufficiency causes intrauterine growth retardation (IUGR) and subsequent low birth weight, which predisposes the affected newborn towards adult Syndrome X. Individuals with Syndrome X suffer increased morbidity from adult ischemic heart disease. Myocardial ischemia initiates a defensive increase in cardiac glucose metabolism, and individuals with Syndrome X demonstrate reduced insulin sensitivity and reduced glucose uptake. Glucose transporters GLUT1 and GLUT4 facilitate glucose uptake across cardiac plasma membranes, and hexokinase II (HKII) is the predominant hexokinase isoform in adult cardiac tissue. We therefore hypothesized that GLUT1, GLUT4 and HKII gene expression would be reduced in heart muscle of growth-retarded rats, and that reduced gene expression would result in reduced myocardial glucose uptake. To prove this hypothesis, we measured cardiac GLUT1 and GLUT4 mRNA and protein in control IUGR rat hearts at day 21 and at day 120 of life. HKII mRNA quantification and 2-deoxyglucose-uptake studies were performed in day-120 control and IUGR cardiac muscle. Both GLUT1 and GLUT4 mRNA and protein were significantly reduced at day 21 and at day 120 of life in IUGR hearts. HKII mRNA was also reduced at day 120. Similarly, both basal and insulin-stimulated glucose uptake were significantly reduced in day-120 IUGR cardiac muscle. We conclude that adult rats showing IUGR as a result of uteroplacental insufficiency express significantly less cardiac GLUT1 and GLUT4 mRNA and protein than control animals (which underwent sham operations), and that this decrease in gene expression occurs in parallel with reduced myocardial glucose uptake. We speculate that this reduced GLUT gene expression and glucose uptake contribute towards mortality from ischemic heart disease seen in adults born with IUGR.
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PMID:Myocardial gene expression of glucose transporter 1 and glucose transporter 4 in response to uteroplacental insufficiency in the rat. 1131 53

Cardiac muscle adaptation is essential for maintaining physical capacity after ascending to high altitude. This study examines the effects of high altitude training on myocardial metabolic enzyme activity and composition of alpha-myosin heavy chain (MHC). Rats were randomly divided into normobaric sedentary (NS) and training (NT) groups, and hypobaric sedentary (HS) and training (HT) groups. HS and HT rats were exposed to hypobaric hypoxia (simulated 4,000-5,000 m) for 5 weeks (24 h/day), and HT rats simultaneously received swim training. Hypoxia exposure for 5 weeks led to a decrease in succinate dehydrogenase (SDH) and citrate synthase (CS) activities in the left ventricle (LV), and a decrease in CS, hexokinase (HK) and total lactate dehydrogenase (LDH) activities in the right ventricle (RV) (p < 0.05, HS vs. NS). Furthermore, 1 h/day swim training during hypoxia exposure enhanced the CS activity in LV and the SDH and CS activities in RV (p < 0.05, HT vs. HS). The percentages of alpha-MHC in both ventricles in HT were higher than those in HS (p < 0.05). We conclude that exercise training at high altitude is beneficial for cardiac muscle adaptation to hypoxia by increasing activities of enzymes and percentage of alpha-MHC. This may contribute to improved cardiac function and work capacity at high altitude.
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PMID:Hypoxic training increases metabolic enzyme activity and composition of alpha-myosin heavy chain isoform in rat ventricular myocardium. 1975 6


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