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)

We have examined the effect of second messengers on ATP-driven H+ transport in an H+ ATPase-bearing endosomal fraction isolated from rabbit renal cortex. cAMP (0.1 mM) had no effect on H+ transport. Acridine orange fluorescence in the presence of 0.5 mM Ca2+ (+1 mM EGTA) was 19 +/- 6% of control. Inhibition of ATP-driven H+ transport by Ca2+ was concentration dependent; 0.25 and 0.5 mM Ca2+ (+1 mM EGTA) inhibited acridine orange fluorescence by approximately 50 and approximately 80%, respectively. Ca2+ also produced a concentration-dependent increase in the rate of pH-gradient dissipation. Ca2+ did not affect ATP hydrolysis. ATP-dependent Br- uptake was virtually unchanged in the presence of 0.5 mM Ca2+ (+1 mM EGTA). These vesicles were also shown to transport Ca2+ in an ATP-dependent mode. Inositol 1,4,5-trisphosphate had no effect on ATP-dependent Ca2+ uptake. These results are consistent with the co-existence of an H+ ATPase and an H+/Ca2+ exchanger on these endosomes, the latter transport system using the H+ gradient to energize Ca2+ uptake. Attempts to demonstrate an H+/Ca2+ antiporter in the absence of ATP have been unsuccessful. Yet, when a pH gradient was established by preincubation with ATP and residual ATP was subsequently removed by hexokinase + glucose, stimulation of Ca2+ uptake could be demonstrated. A Ca2(+)-dependent increase in H+ permeability and an ATP-dependent Ca2+ uptake might have important implications for the regulation of vacuolar H+ ATPase activity as well as the homeostasis of cytosolic Ca2+ concentration.
J Membr Biol 1989 Dec
PMID:H+/Ca2+ exchange in rabbit renal cortical endosomes. 253 22

Concentrations of glycolytic intermediates and adenine nucleotides have been estimated in adductor muscle and hepatopancreas from the sea mussel Mytilus galloprovincialis Lmk. after various periods of valve closure. Mass action ratios of enzyme steps involved in the metabolism of these components are compared with their equilibrium constants. This reveals hexokinase, phosphofructokinase, pyruvate kinase and fructose-1,6-bisphosphatase catalyze non-equilibrium reactions. The changes in the concentrations of the glycolytic intermediates and in the rate M.A.R./Keq during hypoxia suggest that the carbon flow after valve closure is first controlled by phophofructokinase, but later on the rate of transformation of phosphoenolyruvate regulates this flow.
Rev Esp Fisiol 1989 Dec
PMID:[Effect of hypoxia on glycolysis in the adductor muscle and hepatopancreas of the marine mussel Mytilus galloprovincialis Lmk]. 253 27

Polyclonal antibodies raised in rabbits to ATP-requiring enzymes such as 3-phosphoglycerate kinase show cross-reactivity against other unrelated kinases. Our results show that rabbit polyclonal antiserum possesses antibodies that recognize an antigenic site at the ATP binding region of kinases. A classical immunotitration curve was obtained when hexokinase was titrated against anti-myokinase IgG. The immunoinhibitions was reversed in the presence of small concentration of ATP. This cross-reactivity between site specific antibody and unrelated kinase demonstrates the existence of an antigenic site around the ATP binding region. Our proposal of the existence of a common antigenic determinant in the ATP binding region is in agreement with the finding of a common structural domain that binds ATP.
Biochem Int 1989 Dec
PMID:Site specific antibodies directed to the ATP binding region of some kinases. 256 51

Dietary iron deficiency (ID) decreases iron-containing proteins and hence respiratory capacity of skeletal muscle mitochondria (SMM), but noniron components are much less affected. Using a hexokinase plus glucose ATP-utilizing system, we studied control of respiration in isolated SMM from rats of variable iron status: ID, ID 3 days after intraperitoneal treatment with iron dextran, and control. We found that sensitivity of respiratory control (e.g., ATP/ADP at a given oxygen consumption) was positively related to state 3 respiratory capacity. Titration studies with carboxyatractyloside, a noncompetitive inhibitor of adenine nucleotide translocase (AdNT), revealed that AdNT concentration was unaffected by iron status. However, the turnover number of AdNT was markedly reduced by ID and improved with iron treatment. We conclude that in ID SMM, decreased maximal respiratory capacity is paralleled by impaired sensitivity to putative controllers of oxidative phosphorylation at any respiratory rate, despite normal levels of AdNT. A second study was designed to determine possible consequences of impaired sensitivity of respiratory control on motor unit recruitment during exercise. ID and normal rats were subjected to a program of walking treadmill exercise. Although exercise failed to induce any changes in oxidative enzyme levels in control rat, ID animals and exhibited substantial mitochondrial enzyme adaptation in hindlimb skeletal muscle. Furthermore, the most consistent enzymatic changes were observed to occur in fast glycolytic muscle fibers. These results suggest marked alterations in the pattern of muscle fiber recruitment during mild exercise in ID rodents and support the hypothesis that sensitivity of respiratory control in SMM is an important determinant of motor unit recruitment during aerobic exercise.
Am J Physiol 1989 Dec
PMID:Impaired control of respiration in iron-deficient muscle mitochondria. 261 Feb 48

A dimethoxy derivative of leucocyandin 3-O-beta-D-galactosyl cellobioside isolated from the bark of F. bengalensis Linn demonstrated antidiabetic action. On oral administration, it decreased blood sugar very significantly both in normal and moderately diabetic rats and increased serum insulin significantly in the latter at a dosage of 250 mg/kg for a 2 hr period. During one month treatment of the diabetic rats orally with the active principle, at a dosage of 100 mg/kg, there was a significant decrease in blood and urine sugar, certain lipid components in serum and tissues and glucose-6-phosphatase activity in liver, but significant increase in body weight and the activities of hexokinase and HMGCOA reductase in tissues as compared to diabetic control. The mechanism of action of the principle may be related to its protective/inhibitory action against the insulin degradative processes.
Indian J Biochem Biophys 1989 Dec
PMID:Antidiabetic effect of a leucocyanidin derivative isolated from the bark of Ficus bengalensis Linn. 263 65

Saccharomyces cerevisiae mutants containing different point mutations in the HXK2 gene were used to study the relationship between phosphorylation by hexokinase II and glucose repression in yeast cells. Mutants showing different levels of hexokinase activity were examined for the degree of glucose repression as indicated by the levels of invertase activity. The levels of hexokinase activity and invertase activity showed a strong inverse correlation, with a few exceptions attributable to very unstable hexokinase II proteins. The in vivo hexokinase II activity was determined by measuring growth rates, using fructose as a carbon source. This in vivo hexokinase II activity was similarly inversely correlated with invertase activity. Several hxk2 alleles were transferred to multicopy plasmids to study the effects of increasing the amounts of mutant proteins. The cells that contained the multicopy plasmids exhibited less invertase and more hexokinase activity, further strengthening the correlation. These results strongly support the hypothesis that the phosphorylation activity of hexokinase II is correlated with glucose repression.
Mol Cell Biol 1989 Dec
PMID:The residual enzymatic phosphorylation activity of hexokinase II mutants is correlated with glucose repression in Saccharomyces cerevisiae. 268 72

Several hundred new mutations in the gene (HXK2) encoding hexokinase II of Saccharomyces cerevisiae were isolated, and a subset of them was mapped, resulting in a fine-structure genetic map. Among the mutations that were sequenced, 35 were independent missense mutations. The mutations were obtained by mutagenesis of cloned HXK2 DNA carried on a low-copy-number plasmid vector and screened for a number of different phenotypes in yeast strains bearing chromosomal hxk1 and hxk2 null mutations. Some of these mutants were characterized both in vivo and in vitro; they displayed a wide spectrum of residual hexokinase activities, as indicated by three assays: in vitro enzyme activity, ability to grow on glucose and fructose, and ability to repress invertase production when growing on glucose. Of those that failed to support growth on fructose, only a small minority made normal-size, stable, and inactive protein. Analysis of the amino acid changes in these mutants in light of the crystallographically determined three-dimensional structure of hexokinase II suggests important roles in structure or catalysis for six amino acid residues, only two of which are near the active site.
Mol Cell Biol 1989 Dec
PMID:Isolation and characterization of mutations in the HXK2 gene of Saccharomyces cerevisiae. 268 71

In tumoral islet cells (RINm5F line) the phosphorylation of D-fructose is catalyzed by hexokinase rather than fructokinase. Fructose 6-phosphate appears to be preferentially channelled into the pentose cycle, as suggested by a ratio of D-[1-14C]fructose/D-[U-14C]fructose oxidation close to 2.7, the failure to generate 14C-labelled lactate from D-[1-14C]fructose and a poor metabolic response to menadione. When the islet cells are exposed to both D-fructose and D-glucose, however, the metabolism of the former hexose is dramatically modified, fructose 6-phosphate being now formed at a lower rate and preferentially channelled into the glycolytic pathway. These findings illustrate the existence of regulatory steps in fructose catabolism located distally to its site of phosphorylation.
Eur J Biochem 1987 Dec 30
PMID:Fructose metabolism via the pentose cycle in tumoral islet cells. 282 62

Hexokinase (ATP:D-hexose 6-phosphotransferase, EC 2.7.1.1) has been synthesized in the rabbit reticulocyte lysate system directed by poly(A)+ mRNA isolated from rat brain. Identification of the in vitro synthesis product as hexokinase was based on its immunoprecipitation with anti-hexokinase serum as well as the generation of identical peptide maps after partial cleavage of the in vitro product and authentic hexokinase with Staphylococcus aureus V8 proteinase or chymotrypsin. The in vitro product and authentic hexokinase were indistinguishable in molecular weight (SDS-gel electrophoresis); thus, despite the fact that, in situ, much of the hexokinase in brain is found in association with mitochondria, it is not synthesized in the form of a higher molecular weight precursor as is characteristic of other mitochondrial proteins. This is in accord with the view that hexokinase is best considered as a classical 'soluble' enzyme which is capable of exhibiting reversible association with mitochondria. The in vitro product cochromatographs (during anion-exchange HPLC) with authentic hexokinase previously shown to have a blocked (presumably acetylated) N-terminus; this procedure is capable of resolving the N-terminally blocked form of the enzyme from a partially proteolyzed form having a free N-terminal amino group. Thus the in vitro product is apparently N-acetylated by an enzyme system previously shown to be present in reticulocyte lysates. A significant fraction of the in vitro synthesized hexokinase attained a conformation characteristic of the native enzyme as judged by the observations that it could be immunoprecipitated by monoclonal antibodies recognizing the native enzyme but not by antibodies recognizing denatured hexokinase, and limited tryptic cleavage of the in vitro product gave fragments identical to those seen with the native enzyme and thought to reflect the organization of structural domains in that enzyme. However, based on these same criteria, the majority of the hexokinase synthesized in vitro appears to exist in a folding state that is not identical to that of either the fully denatured or native enzyme.
Biochim Biophys Acta 1985 Dec 13
PMID:In vitro synthesis of rat brain hexokinase. 286 81

The axenization of an Entamoeba histolytica isolate with a nonpathogenic isoenzyme electrophoretic pattern (zymodeme) was recently achieved for the first time (15). Forty days after the cells were transferred to the medium used for axenic cultivation, the amebae developed virulence properties, and the zymodeme converted to a pathogenic pattern. To exclude the possibility that the original isolate consisted of two zymodeme populations and that conditions of growth selected for a particular population, the experiment was repeated with a cloned culture of a nonpathogenic (zymodeme III) strain, E. histolytica SAW 1734R clAR, isolated by and obtained from P. G. Sargeaunt. Axenization was accomplished, as before, by transferring trophozoites to TYI-S-33 medium containing a mixture of antibiotics to suppress the growth of the associated bacterial flora and a nutritional supplement consisting of gamma-irradiated bacteria. A change in the hexokinase and phosphoglucomutase isoenzyme pattern was observed 21 days after the amebae had been transferred to the axenic medium but before complete axenization of the amebae had occurred. The change in zymodeme was accompanied by an increase in virulence, as evidenced by the ability of fewer amebae to induce hepatic abscesses in hamsters. A reverse conversion to a nonpathogenic zymodeme was also accomplished by reassociating and subculturing the newly converted pathogenic trophozoites of strain SAW 1734R clAR with the bacterial flora that accompanied this ameba in the original xenic culture. The electromobilities of the hexokinase isoenzymes changed back to their original pattern 7 days after the amebae were returned to xenic growth conditions. Our in vitro results demonstrate that culture conditions and bacterial flora can cause changes in the zymodeme and virulence of a cloned ameba isolate and raise the concern that this could happen also in vivo. Thus, the finding of a particular zymodeme in a culture of E. histolytica isolated from a carrier should not be used to predict a clinical condition or serve as a basis for the recommendation of therapy.
Infect Immun 1986 Dec
PMID:Changes in isoenzyme patterns of a cloned culture of nonpathogenic Entamoeba histolytica during axenization. 287 51


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