Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We show that a rise in cytosolic-free Ca2+ in muscle, induced by Ca(2+)-ionophore A23187 or by the Ca(2+)-mobilizing hormones serotonin, vasopressin, and bradykinin, increases the binding of hexokinase to mitochondria in muscle. This increase could be prevented by treatment with the calmodulin antagonists trifluoperazine or CGS 9343B (a novel, potent, and selective inhibitor of calmodulin activity) which strongly suggests that calmodulin is involved in the Ca(2+)-induced binding of the enzyme to muscle mitochondria.
 ...
PMID:Ca(2+)-ionophore A23187 and the Ca(2+)-mobilizing hormones serotonin, vasopressin, and bradykinin increase mitochondrially bound hexokinase in muscle. 151 75

The effects of calcium antagonists nimodipine, nicardipine and flunarizine on lactate production and specific activities of some enzymes regulating glycolytic flux have been evaluated in synaptosomes isolated from rat whole brain and submitted to in vitro chemical hypoxia induced by rotenone, an inhibitor of mitochondrial respiration. The following enzymes have been tested; hexokinase (ATP: D-hexose-6-phosphotransferase, EC2.7.1.1), phosphofructokinase (ATP: D-fructose-6-phosphate 1-phosphotransferase, EC 2.7.1.11) and pyruvate kinase (ATP: pyruvate 2-O-phosphotransferase, EC 2.7.1.40). The results show that rotenone increases by about eight times the production of lactate; nicardipine and nimodipine, starting from a concentration of 10(-4) M, were able to counteract the rotenone-induced stimulation of glycolysis, but flunarizine was without effect. The dihydropyridines but not flunarizine decreased the maximum activity of phosphofructokinase. This effect was already detectable at a concentration of 10(-5) M. Neither hexokinase nor pyruvate kinase were affected by any of the drugs studied.
 ...
PMID:Effects of calcium antagonists on glycolysis of rat brain synaptosomes. 153 11

The effect of thrombin-activated platelets and their release products on the intracellular free calcium concentration ([Ca2+]i) of human polymorphonuclear leukocytes (PMNs) was studied by loading PMNs with a fluorescent indicator of calcium, fura-2. [Ca2+]i of PMNs was transiently elevated by thrombin-activated platelets. The supernatant of thrombin-activated platelets also elicited a transient elevation of [Ca2+]i in PMNs. Pretreatment of the supernatant with hexokinase caused a decrease in the transient [Ca2+]i elevation of PMNs, while hexokinase abrogated the [Ca2+]i elevation of PMNs elicited by 80 mumol/l adenosine triphosphate (ATP). Pretreatment of the supernatant with trypsin also decreased the magnitude of the elevation, while trypsin had no effect on the response to ATP. These findings suggest that thrombin-activated platelets induce a transient [Ca2+]i elevation in PMNs by releasing ATP and some trypsin-sensitive factor(s).
 ...
PMID:Transient calcium elevation in polymorphonuclear leukocytes triggered by thrombin-activated platelets. 159 99

The ability of the synthetic hypertrehalosemic peptides, HT-I and HT-II, to influence the activities of glycogen phosphorylase, trehalase and hexokinase via elevation of Ca++ and cAMP levels was examined in thoracic musculature of the American cockroach, Periplaneta americana. The peptides effect dose- and time-dependent activation of phosphorylase, trehalase and hexokinase activities that occur concomitantly with elevated levels of intracellular calcium. In addition, HT-I increases the accumulation of cyclic AMP in muscle cells.
 ...
PMID:Stimulation of carbohydrate metabolising enzymes by synthetic hypertrehalosemic peptides in thoracic musculature of the American cockroach, Periplaneta americana. 170 90

A radioactive assay for the determination of pyruvate dehydrogenase complex activity in muscle tissue has been developed. The assay measures the rate of acetyl-CoA formation from pyruvate in a reaction mixture containing NAD+ and CoASH. The acetyl-CoA is determined as [14C]citrate after condensation with [14C]-oxaloacetate by citrate synthase. The method is specific and sensitive to the picomole range of acetyl-CoA formed. In eleven normal subjects, the active form of pyruvate dehydrogenase (PDCa) in resting human skeletal muscle samples obtained using the needle biopsy technique was 0.44 +/- 0.16 (SD) mumol acetyl-CoA.min-1.g-1 wet wt. Total pyruvate dehydrogenase complex (PDCt) activity was determined after activation by pretreating the muscle homogenate with Ca2+, Mg2+, dichloroacetate, glucose, and hexokinase. The mean value for PDCt was 1.69 +/- 0.32 mumol acetyl-CoA.min-1.g-1 wet wt, n = 11. The precision of the method was determined by analyzing 4-5 samples of the same muscle piece. The coefficient of variation for PDCa was 8% and for PDCt 5%.
 ...
PMID:A sensitive radioisotopic assay of pyruvate dehydrogenase complex in human muscle tissue. 179 21

The addition of oligomycin in the presence of Ca2+ increased the ADP pool in mitochondrial suspension. It is suggested that oligomycin inhibition of Ca(2+)-induced mitochondrial respiratory activation is the function of the increased endogenous ADP pool. Low ADP concentrations (5-20 microM) produce the same inhibitory effect as oligomycin. The increase of ADP levels in the presence of glucose plus hexokinase resulted in the inhibition of Ca(2+)-induced respiration, while the addition of phosphoenol pyruvate plus pyruvate kinase followed by a reduction in ADP levels, reversed the oligomycin inhibitory effect. One of the essential stages of ADP accumulation in mitochondrial suspensions in the presence of oligomycin and Ca2+ is proposed to be the formation of ADP from AMP and ATP, effected by adenylate kinase.
 ...
PMID:On the mechanism of oligomycin inhibition of Ca(2+)-induced mitochondrial respiration. 191 91

The regulation of intracellular calcium uptake and release in cultured gastric smooth muscle cells was studied in saponin-permeabilized cells derived from the rabbit antrum. Cells were studied in an ATP-regenerating medium in which the value of the ATP-to-ADP ratio was fixed by variation of the relative concentrations of creatine and creatine phosphate in the presence of a constant concentration of adenine nucleotides and creatine kinase. Free calcium in the medium was measured through the use of the fluorescent probe fura-2. As the ratio of ATP/ADP was increased (8.5, 55.0, and 155.0), the rate of calcium sequestration was increased, resulting in a decrease of steady-state free calcium (275.2, 178.4, and 98.1 nM, respectively). The addition of glucose (5 mM) and hexokinase (15 U/ml), which results in an increase of ADP due to the phosphorylation of glucose in the medium, caused an increase of free calcium concentration to a new set point of approximately 400 nM. Mitochondrial blockade with antimycin A before permeabilization had no effect on calcium sequestration or the resultant free calcium concentration, indicating that under physiological conditions calcium is sequestered predominantly into nonmitochondrial storage sites. Specific variation of ATP/ADP had no effect on the concentration dependence of inositol trisphosphate-induced calcium efflux, suggesting the functional independence of intracellular calcium influx and efflux pathways. These results indicate a significant role for cytoplasmic ATP/ADP in the control of intracellular calcium sequestration and the regulation of steady-state calcium concentration in cultured gastrointestinal smooth muscle cells.
 ...
PMID:ATP-dependent control of steady-state cytosolic calcium in cultured gastric smooth muscle. 192 49

To study the mechanical properties of various crossbridge states in the anterior byssus retractor muscle (ABRM) of Mytilus, the tension response of the glycerinated ABRM to a step increase of the length was examined in rigor solutions with saturating Ca2+ (Rca) and without added Ca2+ (R), rigor ones with ADP (AD) and with both ADP and saturating Ca2+ (ADca), and a low ATP, activating one. The application of ADca to a rigor ABRM caused a slow tension development of less than 0.083 kg/cm2 (n = 6) probably because of contaminant ATP in the presence of 0.25 mM p,p-di(adenosine-5')pentaphosphate (Ap5A) and 10 U/ml hexokinase with 2 mM glucose. The instantaneous stiffness in ADca was slightly smaller than that in the low ATP solution and greater than those in R, Rca, and AD, giving evidence that the stretch response reflected the mechanical property of the crossbridges. The rate of the tension decay during the initial 5 ms after the length change was completed was slowest in the ADca among the solutions examined, while during the initial 30-90 ms it was faster in the low ATP solution than R, Rca, AD, and ADca with little difference of the rate in the latter four solutions. The difference in the time course of the tension decay in between the low ATP solution and ADca may be taken to indicate that the high stiffness in ADca was not due to the formation of the tension-generating crossbridges but to the crossbridges with both bound Ca and ADP (AMCaADP) made directly from the rigor crossbridge (AM). Consequently, it was thought that AMCaADP was stiffer than AM and the crossbridges with either bound Ca (AMCa) or ADP (AM.ADP), the latter three kinds of the crossbridges being formed directly from AM, not as a result of ATP hydrolysis.
 ...
PMID:Effects of calcium and ADP on tension responses to step length increases in glycerinated Mytilus smooth muscle. 196 Aug 88

Administration of vasopressin and glucagon evokes a transient release of Ca2+ from perfused livers. The Ca2+ is released from a pool that is depletable by the mitochondrial uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP). Therefore, the mechanism of the FCCP-stimulated Ca2+ release was examined. The FCCP-stimulated Ca2+ release was associated with a decrease in ATP levels. In the presence of oligomycin, which blocked the FCCP-induced rapid ATP breakdown, FCCP did not release Ca2+ though it still stimulated respiration. The possibility that FCCP might indirectly cause a release of Ca2+ by lowering hepatic ATP was examined at two levels of organization: 1) in the whole organ, by perfusing livers with fructose, a compound that was shown previously to drastically lower ATP in the liver, and 2) in isolated microsomal vesicles by depleting ATP with glucose and hexokinase. Fructose evoked Ca2+ release from the perfused liver. Similarly, depletion of ATP by the addition of glucose and hexokinase evoked a rapid release of the accumulated Ca2+ from microsomal vesicles probably by the inhibition of the Ca2(+)-ATPase. These results demonstrate that the major mechanism by which FCCP releases Ca2+ in intact cells is by lowering ATP levels.
 ...
PMID:Hormonal stimulation of Ca2+ release from the perfused liver: effects of uncoupler. 210 59

Photolysis of nitr-5, a caged calcium molecule, has been used for rapid activation of skinned fibre bundles of a myosin-regulated muscle, the striated adductor of the scallop, Pecten maximus. Chemically skinned fibre bundles (diameter 70-200 microns) were equilibrated in solutions containing 1-3 mM nitr-5 (pCa 6.1) and then activated by ultraviolet laser pulse (25 ns). Pulse energies of 60-95 mJ gave contractions of over 90% maximum tension and a mean half-time for tension rise of 43 ms (n = 4) at 12 degrees C. Electrically stimulated bundles of intact fibres develop a tetanus with a rise half-time of 60.2 ms at 10 degrees C (n = 5) (Rall, J.A. (1981) J. Physiol. 321, 287-295, and personal communication). At lower pulse energies the skinned fibres gave smaller amplitude contractions with slower rates of rise (up to 260 ms half-time). In addition, a slower component of tension development (mean rise half-time 13.3 s) was often observed. In ATP-free solutions containing hexokinase and glucose, rigour tension developed with a delayed onset. Rapid release of ATP (0.47-0.59 mM) from photolysis of caged ATP (2 mM) at pCa 4.5 then caused a rapid contraction with a mean half-time for tension development of 17 ms (n = 4). The fast activation rates obtained by the photorelease of Ca2+ from nitr-5 are similar to those obtained with skinned skeletal fibres of actin-regulated muscle. The results imply that the rate-limiting step in excitation-contraction coupling of the scallop muscle is not the increase in sarcoplasmic Ca2+, but rather the activation of the muscle in response to this increase. The half-times of ATP-induced contractions at pCa 4.5 suggest that in a contraction activated by a rapid Ca2+ jump the process comprising ATP hydrolysis and cross-bridge cycling occurs at a somewhat faster rate than the Ca2(+)-dependent activation process which precedes it.
 ...
PMID:Rapid activation by photolysis of nitr-5 in skinned fibres of the striated adductor muscle from the scallop. 211 54


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>