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)

Analysis of the ischemic dog heart preparation described in the preceding paper indicates that it is an analogue in slow motion of the tissue in the center of a cardiac infarct. It is respiring very slowly and not capable of performing mechanical work. Glycolysis starts up with both glucose and glycogen as inputs. Later hexokinase and to some extent phosphofructokinase become limiting owing to inhibitor accumulation or acidosis. Metabolism then results primarily from cAMP-driven glycogenolysis, largely limited by the glycogen debranching enzymes at later times, with accumultion not only of lactate and alpha-glycerophosphate but of glucose as well. Amino acid levels oscillate with time while fatty acids accumulate at late times. The elevation of cAMP at later times may involve disturbances in its metabolism as well as mechanisms such as adenosine accumulation that are more important in cardiac ischemia than in normal heart. The clinical implications of this behavior are discussed.
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PMID:Metabolism of totally ischemic excised dog heart. II. Interpretation of a computer model. 22 80

Histologic investigations together with histochemical and photometric measurements of enzyme activities were performed in retina of rabbits, whose blood supply had been totally interrupted for 1h. A retinal edema developed affecting the internal layers between the inner limiting membrane and the internal plexiform and ganglion cell layer. Although this edema was quite remarkable at the posterior pole of the eye, it diminished toward the periphery, disappearing near the ora serrata. The activities of the following enzymes were investigated: hexokinase, glucose 6-phosphate dehydrogenase, aldolase, glyceraldehydephosphate dehydrogenase, lactate dehydrogenase, malate dehydrogenase, succinate dehydrogenase, ATPase, and phosphorylase. The most striking finding was the total disappearance of phosphorylase activity under pressure ischemia. ATPase and aldolase showed a decreased activity in the ischemic retina, and malate dehydrogenase a slightly diminished one. Concerning the other enzymes, no significant differences between normal and ischemic retina were observed.
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PMID:Enzymologic and histologic investigations in normal and pressure-ischemic retina of rabbits. 108 79

Heterogenous stock mice in addition to mice selectively bred to maximally differ in their severity of alcohol withdrawal seizures (withdrawal seizure-resistant (WSR) and withdrawal seizure-prone (WSP] were used to provide evidence in favor of the importance of the rapidly changing distribution of brain hexokinase (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1) (HK). An ischemic response at 15, 30, 60 and 120 s after killing showed a decreasing cerebellar cytosolic HK concentration of 31%, 15%, 14% and 10% while the cerebral concentrations were 23%, 13%, 13% and 14%, respectively. WSR and WSP mice given an acute i.p. dose of 4 g/kg of alcohol showed opposite HK responses. Cytosolic HK in WSR mice decreased 18.5%, while WSP mice showed an increase of 20.3% over paired saline-injected controls. When ischemia was allowed to proceed in WSP mice following an in vivo alcohol treatment, cytosolic HK decreased in parallel to mice not given alcohol. These data suggest that alcohol can cause an HK redistribution in vivo which could play a role in the differing sensitivities of WSR and WSP mice to alcohol related seizures.
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PMID:Hexokinase redistribution in vivo. 232 57

Under effects of myocardial ischemia (30 min), the activities of the intermembrane enzymes of rabbit heart mitochondria, i.e., adenylate kinase and creatine kinase, are inhibited by 20% and 23%, respectively. Consequently, the creatine- and AMP-activated respiration of mitochondria diminishes by 52% and 39%, respectively. An inhibitory analysis of ADP-, AMP- and creatine-activated mitochondrial respiration performed in the presence of atractyloside has demonstrated that ischemia (30 min), adriblastin (0.688 mM) and succinate (10 mM) cause alterations in the functional coupling of adenylate kinase and creatine kinase with the adenine nucleotide translocator. These alterations lead to the diminution of the rate and efficiency of energy transfer from mitochondria to hexokinase, as an arbitrary site of energy consumption. An addition of cytochrome c to ischemic heart mitochondria results in an increase in the rate of ATP synthesis; however, the efficiency of this process is lowered. The toxic effect of the anticancer drug--adriblastin on heart mitochondria respiration is enhanced in the presence of creatine in the bathing solution.
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PMID:[Functional changes in the mitochondrial site of adenylate kinase and creatine kinase systems of energy transport induced by myocardial ischemia and adriablastin]. 284 Jan 29

These studies addressed the question of the in vivo distribution of rat brain hexokinase (HK), and whether physiologically relevant changes in the glycolytic rate are accompanied by changes in the distribution of HK. Homogenates of fresh tissue showed only 11-15% of the overt (assayable without added detergent) HK to be soluble (found in high-speed centrifugation supernatant fractions) when homogenization was begun within 15-20 s of sacrifice. Freeze-blown rat brain tissue also was used, coupled with a new technique wherein it was homogenized as it thawed in a buffered sucrose solution containing 1 mM EDTA. In tissue sampled 15 min (anesthetized) or 60 min (waking) after ip Nembutal injection (40 mg/kg), 23% of the overt HK and 79% of the total lactate dehydrogenase were soluble. The average phosphocreatine content of these and similar homogenates had decreased only 23% from in vivo levels, while ATP had decreased by 65%, due to the combined effects of a high level of endogenous ATPase, chelation of Mg2+ by EDTA, and the greater stability of Mg-ATP2- relative to Mg-ADP1-. These data indicated that the tissue experienced, at most, the equivalent of 6 s of complete ischemia prior to the completion of homogenization. Synaptosomes derived from rat and chicken cerebra were incubated at 37 degrees C in a physiological salt solution containing 10 mM glucose. Addition of veratridine has been shown to stimulate glycolysis and oxidative phosphorylation two- to threefold (H. T. Kyriazi and R. E. Basford (1986) J. Neurochem., in press), but did not alter the HK distribution, as 21% was found in the supernatant fractions of both control and veratridine-stimulated synaptosomes treated with digitonin. These results indicate that in brain tissue, large net movements of HK on and off the outer mitochondrial membrane do not occur, and thus play no role in the regulation of glycolysis.
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PMID:An examination of the in vivo distribution of brain hexokinase between the cytosol and the outer mitochondrial membrane. 294 9

The metabolism of 2-deoxyglucose has been studied in 540 micron and 1,000 micron hypothalamic brain slices. Slice 2-deoxyglucose (2DG) and 2-deoxyglucose-6-phosphate (2DG6P) levels were measured after tissue homogenization and perchloric acid extraction. By analyzing the uptake and washout kinetics with nonlinear least-squares methods, we have determined the rate constants for three-, four-, or five-parameter kinetic models and obtained a value for the in vitro lumped constant (LC). The kinetic analysis reveals a small, slowly decaying, 2DG component that is not predicted by any of the models. If this component is treated as a separate, parallel compartment, then the four- and five-parameter models are essentially equivalent. To compare our data to prior in vivo data, we combined 2DG and 2DG6P to produce Ci*, the total slice radioactivity, and analyzed the first 45 min of uptake. These data were fit best by a three-parameter model and the slowly decaying pool was not identified. Calculation of glucose utilization from total tissue radioactivity, measured by whole slice homogenization and by image analysis of autoradiograms, showed excellent correlation between the two methods. Image analysis of radioactivity in the suprachiasmatic nucleus, which is present in these slices, revealed a spontaneous diurnal variation in in vitro glucose utilization in close quantitative agreement with prior in vivo measurements. The kinetic analysis of the 1,000 micron slice was qualitatively similar to that of the 540 micron slice but revealed an increase in the LC and a large decrease in k1 as well as the expected large increase in the hexokinase rate constant, k3. Overall, in vitro glucose utilization increased by about 60%. These results are consistent with our prior studies of the 1,000 micron slice and support our interpretation that the 1,000 micron slice is an excellent in vitro model for brain ischemia without infarction.
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PMID:Brain slice glucose utilization. 318 59

It is shown in experiments on rats that the early postischemic period after 1- and 1.5-hour ischemia of kidneys is characterized by a decrease in the damage of the glycolytic system site which induces glucose-6-phosphate transformation into lactate and by an increase in the inhibition intensity of the initial hexokinase reaction of glycolysis. In the postischemic period after more prolonged (2-, 3-hour) ischemia the damage of the glycolytic system develops also at the site of glucose-6-phosphate transformation into lactate. Administration either of the nucleotide complex (NAD and AMP) or calmodulin inhibitors (aminazine and zinc sulphate) to rats prior to two-hour occlusion of kidneys vessels promotes a decrease in the inhibition of the glycolytic system activity in the postischemic period. At the same time the separate and combined application of zinc sulphate and triftazin (the most intensive calmodulin inhibitor) is not efficient. The positive effect of NAD, AMP and aminazine on the state of the glycolytic kidney system in the postischemic period correlates with the improvement of the blood microcirculation processes in them.
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PMID:[Glycolysis in the rat kidney shortly after ischemia and administration of calmodulin inhibitors, AMP and NAD]. 379 79

In Mongolian gerbils (Meriones unguiculatus) cerebral ischemia was produced by occlusion of the right common and the left external carotid arteries. Gerbils were classified according to their neurological appearance as "symptom-negative" (8 animals), "mild symptoms" (unilateral hemiparesis, 10 animals) and "severe symptoms" (hemiparesis and rolling seizures, 8 animals). Two hours after vascular occlusion various substrates and enzymes related to the energy-producing metabolism, were assessed in tissue samples from both hemispheres. In symptom-negative animals, the only change was a slight decrease of glycolytic intermediates in the right hemisphere. In animals with mild symptoms, the right hemisphere additionally exhibited an impairment of the redox and energy state and an enhancement of the activity of most enzymes of the glycolytic pathway, except hexokinase. In animals with severe symptoms, these changes were even more pronounced and affected--to a lesser degree--also the left hemisphere. The results obtained demonstrate that the neurological appearance of the animals after vascular occlusion correlates with the biochemical alterations and, therefore, can be used for estimating the density of graded ischemia.
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PMID:Biochemical changes during graded brain ischemia in gerbils. Part 1. Global biochemical alterations. 622 Oct 81

The maximal rate of some cerebral enzymatic activities related to energy transduction (hexokinase; phosphofructokinase; lactate dehydrogenase; citrate synthase; malate dehydrogenase; total NADH-cytochrome c reductase; cytochrome oxidase), amino acid metabolism (glutamate decarboxylase; glutamate dehydrogenase) and cholinergic metabolism (acetylcholine esterase) were tested in the cerebral cortex and in sub-cortical area of rats. The evaluations were performed both in the homogenate in toto and in the crude mitochondrial fraction, before and after a postdecapitative normothermic ischemia of 5, 10, 20, and 40 min duration. The results are discussed also with respect to the pharmacological pretreatment with two biological substances which may modulate amino acid (L-alanine) and phospholipid metabolism (CDP-choline). The analysis of the present data suggests the occurrence in brain tissue of a variety of interrelated factors implicated in the ischemia-induced changes of the maximal rate of the enzymatic activities related to the energy transduction. These include: (a) rearrangement of the enzymatic activities because of the changed metabolic and chemico-physical condition; (b) decrease in the activity of enzymes related to the electron transfer chain and glycolysis; (c) changes in enzymes related to mitochondrial membranes. The effects of in vivo administration of alanine or CDP-choline, even if significant, are not consistent throughout the time period studied.
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PMID:Changes induced by ischemia on some cerebral enzymatic activities related to energy transduction and amino acid metabolism. 685 30

Construction and fit to experimental data of a computer model of glycolysis, the tricarboxylic acid cycle, and related metabolism in the perfused rat heart involving 63 enzyme submodels is described. The experimental preparation simulated is a rat heart perfused with Krebs bicarbonate solution containing glucose and insulin whose pH was lowered to 6.6 by equilibration with 35% CO2-65% O2. The glycolytic rate falls sharply and ischemia results, becoming apparent after 3.5 min. The model initially ascribes the fall in glycolysis largely to inhibition of hexokinase by accumulated glucose 6-phosphate and inactivation of phosphofructokinase by the low pH and subsequently to cytoplasmic glucose depletion owing to limitation of glucose uptake by the external acidosis. At the same time there is insufficiently deep hypoxia to trigger substantial mobilization of endogenous fuels (e.g., glycogenolysis or fatty acid mobilization, so that these hearts become ischemic primarily owing to a shortage of metabolic fuel.
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PMID:Computer simulation of energy metabolism in acidotic cardiac ischemia. 708 79


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