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 rates of ATP synthesis and release by the dynein ATPase were determined in order to estimate thermodynamic parameters according to the pathway: (Formula: see text). Dynein was incubated with high concentrations of ADP and Pi to drive the net synthesis of ATP, and the rate of ATP production was monitored fluorometrically by production of NADPH through a coupled assay using hexokinase and glucose-6-phosphate dehydrogenase. The turnover number for the rate of release of ATP from 22S dynein was 0.01 s-1 per site at pH 7.0, 28 degrees C, assuming a molecular weight of 750 000 per site. The same method gave a rate of ATP synthesis by myosin subfragment 1 of 3.4 X 10(-4) s-1 at pH 7.0, 28 degrees C. The rate of ATP synthesis at the active site was estimated from the time dependence of medium phosphate-water oxygen exchange. Dynein was incubated with ADP and [18O] Pi, and the rate of loss of the labeled oxygen to water was monitored by 31P NMR. A partition coefficient of 0.31 was determined, which is equal to k-2/(k-2 + k3). Assuming k3 = 8 s-1 [Johnson, K.A. (1983) J. Biol. Chem. 258, 13825-13832], k-2 = 3.5 s-1. From the rates of ATP binding and hydrolysis measured previously (Johnson, 1983), the equilibrium constants for ATP binding and hydrolysis could be calculated: K1 = 5 X 10(7) M-1 and K2 = 14.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Rate of ATP synthesis by dynein. 293 51

In rapidly growing, highly glycolytic hepatoma cells as much as 65% of the total cell hexokinase is bound to the outer mitochondrial membrane [Parry, D.M., & Pedersen, P.L. (1983) J. Biol. Chem. 258, 10904-10912]. In this paper, we describe the purification to apparent homogeneity of a mitochondrial pore-forming protein from the highly glycolytic AS-30D rat hepatoma cell line. The purified protein shows a single 35 000-dalton band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, an amino acid composition slightly more hydrophobic than that of the rat liver pore protein (also known as VDAC or mitochondrial porin), and a channel-forming activity of 136 channels min-1 (microgram of protein)-1. In addition to displaying the properties characteristic of VDAC (single-channel conductance, voltage dependence, and preference for anions), we observe that the AS-30D VDAC protein is one of only three mitochondrial proteins that bind [14C]dicyclohexylcarbodiimide (DCCD) at relatively low dosages (2 nmol of DCCD/mg of mitochondrial protein). Significantly, treatment of intact mitochondria isolated from either rat liver or the AS-30D hepatoma with DCCD results in an almost complete inhibition of their ability to binding hexokinase. Fifty percent inhibition of binding occurs at less than 2 nmol of DCCD/mg of mitochondrial protein. In contrast to DCCD, water-soluble carbodiimides are without effect on hexokinase binding. These results suggest that the pore-forming protein of tumor mitochondria forms at least part of the hexokinase receptor complex. In addition, they indicate that a carboxyl residue located within a hydrophobic region of the receptor complex may play a critical role in hexokinase binding.
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PMID:Hexokinase receptor complex in hepatoma mitochondria: evidence from N,N'-dicyclohexylcarbodiimide-labeling studies for the involvement of the pore-forming protein VDAC. 300 16

The activity of some enzymes in a given metabolic pathway is modulated through multiple mechanisms, which operate in a simultaneous and coherent way to produce either stimulation or inhibition. The operation of these mechanisms is illustrated with several enzymes involved in glucose metabolism, by choosing examples from the presentations at the Symposium. Thus the reciprocal interactions of the regulatory mechanisms acting upon hexokinase D ('glucokinase'), phosphofructokinase, fructose 1,6-bisphosphatase and pyruvate kinase were discussed, as well as their relationships with the induction of enzyme conformational changes. In addition, the effects of covalent interconversions on glutamine synthetase activity were briefly analyzed. An outstanding feature exhibited by all these enzymes is the display of a great number of elasticity coefficients, which are differential quotients measuring the dependence of enzymatic activity on each variable that modulates it. A general assumption is that these enzymes make an important contribution to the control of the metabolic flux in which they participate. The flux control, however, appears to be shared in different degrees by all the components of the system, and may be quantified through the differential quotient denominated control coefficient. Some of the problems that emerge in any attempt to estimate these coefficients in the living cells are discussed. The problems derive partly from the complex subcellular structure, the formation of functional compartments resulting from reversible association of the enzymes, one to another and to different cellular components, and the actual state of cell water. These problems make that the results obtained with purified and highly diluted enzymes in most enzymological studies should not be extrapolated directly to what happens in vivo, without a careful evaluation of each particular case. The regulatory role of enzyme activity of fructose 2,6-bisphosphate and its eventual participation as an intermediary in the hormonal control of glycolytic and gluconeogenic fluxes are emphasized. The regulation of yeast fructose 1,6-bisphosphate activity is discussed in relation to the eventual role of allosteric modulators and covalents interconversions as signals for the initiation of intracellular degradation of the enzyme during catabolic inactivation.
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PMID:[Concurrence of multiple and integrated mechanisms in the modulation of enzyme activities: significance for the regulation of metabolic fluxes]. 301 48

A decreased intracellular pH of exocrine glands could be an important factor in the pathogenesis of cystic fibrosis. Metabolic acidosis was induced in rats by adding ammonium chloride to the drinking water. An increased content of both total proteins and glycoproteins was found in the submandibular glands of the treated animals. The activities of the glycolytic enzymes - hexokinase, phosphofructokinase, pyruvate kinase and lactate dehydrogenase - were also increased in these glands, whereas the activity of creatine phosphokinase was unchanged. The changes of protein concentration and enzyme activities in the submandibular gland of acidotic rats agree with findings in patients with cystic fibrosis and cultured fibroblasts from these patients. The acidotic rat might be a new promising animal model for cystic fibrosis research. The finding of increased enzyme activities in acidotic rats is, however, contrary to findings in other animal models of the disease.
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PMID:Effect of metabolic acidosis on glycolysis in rat submandibular glands. 315 41

Rats were fed 100 microM AlCl3 for 1 year in their drinking water, then killed and their brains homogenized in 0.1 M Tris (pH 7.4). The 800 g supernatants were assayed for Al3+ and the activities of acetylcholine esterase (ACE), hexokinase and glucose-6-phosphate dehydrogenase (G6PDH). The concentrations of Al in the homogenates, as computed on the original brain for the control and Al fed group were 40 ng and 80 ng/g wet wt, respectively. The activity of ACE was the same in both groups but that of hexokinase and G6PDH in the Al-fed group was about 73% and 80%, respectively, of the control. Dialysis restored the G6PDH but increased the hexokinase of the control group 2-fold and that of Al-fed group 2.7-fold. Thus at this elevated level it was same in both groups. The contribution of Al from the undialysed homogenates during assay was too low to account for the inhibition. It is therefore suggested that a dialyzable inhibitor for hexokinase is normally present in the brain and that Al feeding increases its concentration to further inhibit the utilization of glucose.
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PMID:Effect of long-term feeding of aluminium chloride on hexokinase and glucose-6-phosphate dehydrogenase in the brain. 333 83

Two cases of absence status are described, one case following metrizamide myelography and the other from omnipaque myelography. Metrizamide has been well known to cause convulsive seizures even in patients without epilepsy. The exact mechanism is not known but appears to be direct neuronal toxic effects possibly due to competitive inhibition of hexokinase activity. The acute confusional state following myelography from water soluble agents is reviewed. In view of the difficulty in clinical diagnosis and the excellent response to anticonvulsant therapy, the possibility of this clinical entity should be specifically excluded by EEG in any person suffering from prolonged confusion following myelography with water soluble agents.
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PMID:Absence status epilepticus resulting from metrizamide and omnipaque myelography. 339 4

A possibility of hexokinase binding with actomyosin in skeletal muscles of Rana temporaria L., and the effect of thermal alteration (15 min at 36, 37, 38, 40 and 42 degrees C) on the binding were studied. Solutions of KCl (0.075 M and 0.15 M) extract more hexokinase from intact and altered muscles than does an non-electrolyte medium. Hexokinase freely dissolved in hyaloplasm is extracted in non-electrolyte medium. Hexokinase bound with structural components of the muscle cell is extracted upon the increase in ionic force of the extractant. The solubilizing effect of electrolytes on hexokinase is higher in alterated muscles than in the intact muscles indicating the increase in hexokinase binding under thermal alteration. Actomysin isolated from muscles reveals hexokinase activity. In reprecipitated actomyosin, the larger part of its hexokinase remains in actomyosin gel, the level of hexokinase activity not depending on the number of reprecipitation procedures or on the volume of washing solution. Hexokinase in actomyosin gel is less stable to the thermal action than in water supernatant of muscle extract. This may be due to the increase in hexokinase binding with actomiosin whose sorption activity increases under the thermal denaturation.
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PMID:[Nature of the changes in the activity of water-soluble enzymes in exposure of muscles to harmful agents. IV. The study of hexokinase extractability from intact and altered muscles]. 348 10

Metabolic studies using the 2-[14C]deoxy-D-glucose and cytochrome oxidase techniques have demonstrated changes in the activity of central sites associated with the hypothalamoneurohypophysial system in water-deprived (WD) and diabetes insipidus (DI) rats. Another method that may be used as an index of metabolic activity in discrete regions of the central nervous system is the measurement of hexokinase (HK) activity. This study describes changes in metabolic activity, as measured by HK histochemistry, in regions of the forebrain of WD and DI rats. Significant increases in HK activity measured by densitometric analysis were observed in the magnocellular component of the paraventricular nucleus of the hypothalamus, supraoptic nucleus, nucleus circularis, and neurohypophysis of WD and DI rats. In addition, increased HK activity was observed in the preoptic area and subfornical organ of DI rats. These data demonstrate that metabolic changes occur in the forebrain of WD and DI rats within structures involved in body fluid regulation. The present study also demonstrates that HK histochemistry may be used as a marker of metabolic activity in discrete regions of the central nervous system.
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PMID:Increased hexokinase activity in forebrain of water-deprived and diabetes insipidus rats. 374 Mar 8

In 12 patients with paramyotonia congenita, percutaneous needle biopsies from the brachial biceps muscle were performed. Muscle fibre area, distribution of muscle fibre types I, II-A and II-B and capillarization were not different from healthy controls. Signs of myopathy with central nuclei in the muscle cells were noted in 9 of the patients. 4 of these patients also had small areas with degeneration and, in one, vacuoles were observed. Quantitative determination of muscle glycogen, water and protein content were within normal range as were enzyme activities for hexokinase, lactate dehydrogenase, citrate synthetase and 3-hydroxy-acyl-CoA dehydrogenase.
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PMID:Skeletal muscle in paramyotonia congenita: biochemistry, histochemistry and morphology. 397 54

The effect of hypoparathyroidism and low blood calcium on enzyme levels in rat liver and kidney is shown. Four animal groups were used: parathyroidectomized (PTX), PTX with CaCl2 added in the drinking water, sham-operated controls and sham-operated with CaCl2 added in the drinking water. PTX significantly lowered serum parathyroid hormone (PTH) and calcium. Supplementation of CaCl2 in the drinking water increased serum Ca levels in PTX rats but not in the controls. Significant changes in several liver and kidney enzymes were seen. Most affected were the liver NADP dependent enzymes, glucose-6-phosphate dehydrogenase and malic enzyme. Similar patterns but with relatively smaller changes were seen in the liver enzymes, lactic dehydrogenase, hexokinase, and aspartate transferase. No significant differences between the groups were seen in the levels of malic dehydrogenase, isocitric dehydrogenase, fructose-6-phosphate kinase and cholinesterase. In the kidney, which was less affected than the liver, the only significant difference was seen in the level of malic enzyme. Serum total lipids in the PTX group were significantly lower. All the changes seen were partially reversed by Ca supplementation in the drinking water.
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PMID:Biochemical change in the liver and kidney of rats following parathyroidectomy. 400 1


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